WO2003034903B1 - Psma antibodies and protein multimers - Google Patents

Psma antibodies and protein multimers

Info

Publication number
WO2003034903B1
WO2003034903B1 PCT/US2002/033944 US0233944W WO03034903B1 WO 2003034903 B1 WO2003034903 B1 WO 2003034903B1 US 0233944 W US0233944 W US 0233944W WO 03034903 B1 WO03034903 B1 WO 03034903B1
Authority
WO
WIPO (PCT)
Prior art keywords
antigen
binding fragment
psma
antibody
abgenix
Prior art date
Application number
PCT/US2002/033944
Other languages
French (fr)
Other versions
WO2003034903A3 (en
WO2003034903A2 (en
Inventor
Paul J Maddon
Gerald P Donovan
William C Olson
Norbert Schuelke
Jason Gardner
Dangshe Ma
Original Assignee
Psma Dev Company L L C
Paul J Maddon
Gerald P Donovan
William C Olson
Norbert Schuelke
Jason Gardner
Dangshe Ma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27407041&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2003034903(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to AU2002356844A priority Critical patent/AU2002356844C1/en
Priority to JP2003537481A priority patent/JP5355839B2/en
Priority to CA2464239A priority patent/CA2464239C/en
Priority to EP02802198A priority patent/EP1448588A4/en
Application filed by Psma Dev Company L L C, Paul J Maddon, Gerald P Donovan, William C Olson, Norbert Schuelke, Jason Gardner, Dangshe Ma filed Critical Psma Dev Company L L C
Priority to US10/395,894 priority patent/US7850971B2/en
Publication of WO2003034903A2 publication Critical patent/WO2003034903A2/en
Priority to US10/695,667 priority patent/US20040161776A1/en
Publication of WO2003034903A3 publication Critical patent/WO2003034903A3/en
Publication of WO2003034903B1 publication Critical patent/WO2003034903B1/en
Priority to US10/976,352 priority patent/US20050215472A1/en
Priority to US11/983,372 priority patent/US8114965B2/en
Priority to US12/845,686 priority patent/US8470330B2/en
Priority to US13/608,337 priority patent/US9695248B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1093—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies
    • A61K51/1096—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies radioimmunotoxins, i.e. conjugates being structurally as defined in A61K51/1093, and including a radioactive nucleus for use in radiotherapeutic applications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A61K47/6819—Plant toxins
    • A61K47/6825—Ribosomal inhibitory proteins, i.e. RIP-I or RIP-II, e.g. Pap, gelonin or dianthin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6869—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A61K51/1072—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants the tumor cell being from the reproductive system, e.g. ovaria, uterus, testes or prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)

Abstract

The invention includes antibodies or antigen-binding fragments thereof which bind specifically to conformational epitopes on the extracellular domain of PSMA, compositions containing one or a combination of such antibodies or antibodies or antigen-binding fragments thereof, hybridoma cell lines that produce the antibodies, and methods of using the antibodies or antigen-binding fragments thereof for cancer diagnosis and treatment. The invention also includes oligomeric forms of PSMA proteins, compositions comprising the multimers, and antibodies that selectively bind to the multimers.

Claims

AMENDED CLAIMS
[received by the International Bureau on 23 May 2003 (23.05.03); original claims 12-384 replaced by amended claims 13-385; remaining claims unchanged (46 pages)]
Abgenix 4.28.3, Abgenix 4.40.2, Abgenix 4.48.3, Abgenix 4.49.1, Abgenix 4.209.3, Abgenix 4.219.3, Abgenix 4.288.1 , Abgenix 4.333.1, Abgenix 4.54.1, Abgenix 4.153.1, Abgenix 4.232.3, Abgenix 4.292.3, Abgenix 4.304.1, Abgenix 4.78.1, Abgenix 4.152.1 and antigen- binding fragments thereof.
9. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of antibodies comprising:
(a) a heavy chain encoded by a nucleic acid molecule comprising the heavy chain coding region or regions of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as SEQ ID NOs: 2-7, and
(b) a light chain encoded by a nucleic acid molecule comprising the light chain coding region or regions of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as SEQ ID NOs: 8-13, and antigen-binding fragments thereof.
10. The isolated antibody or antigen-binding fragment of claim 9, wherein the second antibody comprises:
(a) a heavy chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 2, and
(b) a light chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 8.
11. The isolated antibody or antigen-binding fragment of claim 9, wherein the second antibody comprises:
(a) a heavy chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 3, and
(b) a light chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 9.
12. The isolated antibody or antigen-binding fragment of claim 9, wherein the second antibody comprises: (a) a heavy chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 4, and
(b) a light chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 10.
13. The isolated antibody or antigen-binding fragment of claim 9, wherein the second antibody comprises:
(a) a heavy chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 5, and (b) a light chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 11.
14. The isolated antibody or antigen-binding fragment of claim 9, wherein the second antibody comprises: (a) a heavy chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 6, and
(b) a light chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 12.
15. The isolated antibody or antigen-binding fragment of claim 9, wherein the second antibody comprises:
(a) a heavy chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 7, and
(b) a light chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 13.
16. An isolated antibody which specifically binds to an extracellular domain of prostate specific membrane antigen, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 90% identical to the nucleotide sequence encoding the antibody of claim 9.
17. The isolated antibody of claim 16, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 95% identical.
18. The isolated antibody of claim 16, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 97% identical.
19. The isolated antibody of claim 16, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 98% identical.
20. The isolated antibody of claim 16, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 99% identical.
21. An antigen-binding fragment of the isolated antibody of claim 9, comprising:
(a) a heavy chain variable region encoded by a nucleic acid molecule comprising the coding regions or regions of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as: SEQ ID NOs: 14, 18, 22, 26 and 30, and (b) a light chain variable region encoded by a nucleic acid molecule comprising the coding region or region of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as: SEQ ID NOs: 16, 20, 24, 28 and 32.
22. An antigen-binding fragment of the isolated antibody of claim 21, comprising: (a) a heavy chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 14, and
(b) a light chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 16.
23. An antigen-binding fragment of the isolated antibody of claim 21 , comprising:
(a) a heavy chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 18, and
(b) a light chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 20.
24. An antigen-binding fragment of the isolated antibody of claim 21, comprising:
(a) a heavy chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 22, and (b) a light chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 24.
25. An antigen-binding fragment of the isolated antibody of claim 21, comprising: (a) a heavy chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 26, and
(b) a light chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 28.
26. An antigen-binding fragment of the isolated antibody of claim 21, comprising:
(a) a heavy chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 30, and
(b) a light chain variable region encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence set forth as SEQ ID NO: 32.
27. The antigen-binding fragment of the isolated antibody of claim 9, comprising:
(a) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of amino acid sequences set forth as: SEQ ID NOs: 15, 19, 23, 27 and 31 , and (b) a light chain variable region comprising an amino acid sequence selected from the group consisting of nucleotide sequences set forth as: SEQ ID NOs: 17, 21, 25, 29 and 33.
28. An antigen-binding fragment of the isolated antibody of claim 27, comprising:
(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 15, and
(b) a light chain variable region comprising an amino acid set forth as SEQ ID NO: 17.
29. An antigen-binding fragment of the isolated antibody of claim 27, comprising: (a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ
ID NO: 19, and
(b) a light chain variable region comprising an amino acid set forth as SEQ ID NO: 21.
30. An antigen-binding fragment of the isolated antibody of claim 27, comprising:
(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 23, and (b) a light chain variable region comprising an amino acid set forth as SEQ ID NO:
25.
31. An antigen-binding fragment of the isolated antibody of claim 27, comprising:
(a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 27, and
(b) a light chain variable region comprising an amino acid set forth as SEQ ID NO: 29.
32. An antigen-binding fragment of the isolated antibody of claim 27, comprising: (a) a heavy chain variable region comprising an amino acid sequence set forth as SEQ
ID NO: 31, and
(b) a light chain variable region comprising an amino acid set forth as SEQ ID NO:
33.
33. An isolated antigen-binding fragment which comprises a CDR of the antigen-binding fragment according to claim 21 or claim 27.
34. The isolated antigen-binding fragment of claim 33, wherein the CDR is CDR3.
35. An expression vector comprising an isolated nucleic acid molecule encoding the isolated antibody or antigen-binding fragment of any one of claims 1-34.
36. An expression vector comprising an isolated nucleic acid molecule encoding the heavy chain of AB-PGl-XG 1 -006 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 2.
37. An expression vector comprising an isolated nucleic acid molecule encoding the light chain of AB-PGl-XG 1-006 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 8.
38. An expression vector comprising an isolated nucleic acid molecule encoding the heavy and light chains of AB-PGl-XG 1-006 encoded by the nucleic acid molecules comprising the coding region or regions of the nucleotide sequences set forth as SEQ ID NOs: 2 and 8.
39. An expression vector comprising an isolated nucleic acid molecule encoding the heavy chain of AB-PGl-XG 1-026 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 3.
40. An expression vector comprising an isolated nucleic acid molecule encoding the light chain of AB-PGl-XG 1-026 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 9.
41. An expression vector comprising an isolated nucleic acid molecule encoding the heavy and light chains of AB-PGl-XG 1-026 encoded by the nucleic acid molecules comprising the coding region or regions of the nucleotide sequences set forth as SEQ ID NOs: 3 and 9.
42. An expression vector comprising an isolated nucleic acid molecule encoding the heavy chain of AB-PGl-XG 1-051 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 4.
43. An expression vector comprising an isolated nucleic acid molecule encoding the light chain of AB-PGl-XG 1-051 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 10.
44. An expression vector comprising an isolated nucleic acid molecule encoding the heavy and light chains of AB-PGl-XG 1-051 encoded by the nucleic acid molecules comprising the coding region or regions of the nucleotide sequences set forth as SEQ ID NOs: 4 and 10.
45. An expression vector comprising an isolated nucleic acid molecule encoding the heavy chain of AB-PGl-XG 1-069 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 5.
46. An expression vector comprising an isolated nucleic acid molecule encoding the light chain of AB-PGl-XG 1-069 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 11.
47. An expression vector comprising an isolated nucleic acid molecule encoding the heavy and light chains of AB-PGl-XG 1-069 encoded by the nucleic acid molecules comprising the coding region or regions of the nucleotide sequences set forth as SEQ ID NOs: 5 and 11.
48. An expression vector comprising an isolated nucleic acid molecule encoding the heavy chain of AB-PGl-XG 1-077 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 6.
49. An expression vector comprising an isolated nucleic acid molecule encoding the light chain of AB-PGl-XG 1-077 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 12.
50. An expression vector comprising an isolated nucleic acid molecule encoding the heavy and light chains of AB-PGl-XG 1-077 encoded by the nucleic acid molecules comprising the coding region or regions of the nucleotide sequences set forth as SEQ ID NOs: 6 and 12.
51. An expression vector comprising an isolated nucleic acid molecule encoding the heavy chain of AB-PGl-XG 1-006 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 7.
52. An expression vector comprising an isolated nucleic acid molecule encoding the light chain of AB-PG1-XG1-006 encoded by a nucleic acid molecules comprising the coding region or regions of the nucleotide sequence set forth as SEQ ID NO: 13.
53. An expression vector comprising an isolated nucleic acid molecule encoding the heavy and light chains of AB-PG 1-XG1 -006 encoded by the nucleic acid molecules comprising the coding region or regions of the nucleotide sequences set forth as SEQ ID NOs: 7 and 13.
54. A host cell transformed or transfected by the expression vector of claim 35.
55. A plasmid which produces the antibody or antigen binding fragments of any one of claims 1-34.
56. The plasmid of claim 55, wherein the plasmid is selected from the group consisting of: AB-PGl-XG 1-006 Heavy Chain (SEQ ID NO: 2), AB-PGl-XG 1-006 Light Chain (SEQ ID NO: 8), AB-PG1-XG1-026 Heavy Chain (SEQ ID NO: 3), AB-PGl-XG 1-026 Light Chain (SEQ ID NO: 9), AB-PG1-XG1-051 Heavy Chain (SEQ ID NO: 4), AB-PG1-XG1- 051 Light Chain (SEQ ID NO: 10), AB-PGl-XG 1 -069 Heavy Chain (SEQ ID NO: 5), AB- PG 1 -XG 1 -069 Light Chain (SEQ ID NO: 1 1 ), AB-PG 1 -XG 1 -077 Heavy Chain (SEQ ID NO: 6), AB-PGl-XG 1 -077 Light Chain (SEQ ID NO: 12), PSMA 10.3 Heavy Chain (SEQ ID NO: 7), and PSMA 10.3 Kappa (SEQ ID NO: 13).
57. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or antigen-binding fragment thereof is selected for its ability to bind live cells.
58. The isolated antibody or antigen-binding fragment thereof of claim 57 , wherein the cell is a tumor cell.
59. The isolated antibody or antigen-binding fragment thereof of claim 58, wherein the tumor cell is a prostate tumor cell.
60. The isolated antibody or antigen-binding fragment thereof of claim 59, wherein the tumor cell is a LNCaP cell.
61. The isolated antibody or antigen-binding fragment thereof according to claim 1 , wherein said antibody or antigen-binding fragment thereof mediates cytolysis of cells expressing PSMA.
62. The isolated antibody or antigen-binding fragment thereof of claim 61 wherein cytolysis of cells expressing PSMA is mediated by effector cells.
63. The isolated antibody or antigen-binding fragment thereof of claim 61 wherein cytolysis of cells expressing PSMA is complement mediated in the presence of effector cells.
64. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or antigen-binding fragment thereof inhibits the growth of cells expressing PSMA.
65. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or antigen-binding fragment thereof does not require cell lysis to bind to the epitope on PSMA.
66. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgAsec, IgD, IgE or has immunoglobulin constant and/or variable domain of IgGl, IgG2, IgG3, IgG4, IgM, IgAl, lgA2, IgAsec, IgD or IgE.
67. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody is a recombinant antibody.
68. The isolated antibody or antigen-binding fragment thereof according to claim 1 , wherein said antibody is a polyclonal antibody. 150
69. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody is a monoclonal antibody.
70. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody is a humanized antibody.
71. The isolated antibody or antigen-binding fragment thereof according to claim 70, wherein said antibody is a monoclonal antibody.
72. The isolated antibody or antigen-binding fragment thereof according to claim 70, wherein said antibody is a polyclonal antibody.
73. The isolated antibody or antigen-binding fragment thereof according to claim 70, wherein said antibody is a mixture of monoclonal and/or polyclonal antibodies.
74. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody is a chimeric antibody.
75. The isolated antibody or antigen-binding fragment thereof according to claim 74, wherein said antibody is a monoclonal antibody.
76. The isolated antibody or antigen-binding fragment thereof according to claim 74, wherein said antibody is a polyclonal antibody.
77. The isolated antibody or antigen-binding fragment thereof according to claim 74, wherein said antibody is a mixture of monoclonal and/or polyclonal antibodies.
78. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody is a human antibody.
79. The isolated antibody or antigen-binding fragment thereof according to claim 78, wherein said antibody is a monoclonal antibody. 151
80. The isolated antibody or antigen-binding fragment thereof according to claim 78, wherein said antibody is a polyclonal antibody.
81. The isolated antibody or antigen-binding fragment thereof according to claim 78, wherein said antibody is a mixture of monoclonal and/or polyclonal antibodies.
82. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody is a bispecific or multispecific antibody.
83. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the isolated antigen-binding fragment is selected from the group consisting of a Fab fragment, a F(ab')2 fragment, and a Fv fragment CDR3.
84. The isolated antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody is a monoclonal antibody produced by a hybridoma cell line selected from the group consisting of PSMA 3.7 (PTA-3257), PSMA 3.8, PSMA 3.9 (PTA-3258), PSMA 3.11 (PTA-3269), PSMA 5.4 (PTA-3268), PSMA 7.1 (PTA-3292), PSMA 7.3 (PTA- 3293), PSMA 10.3 (PTA-3247) , PSMA 1.8.3 (PTA-3906), PSMA A3.1.3 (PTA-3904), PSMA A3.3.1 (PTA-3905), Abgenix 4.248.2 (PTA-4427), Abgenix 4.360.3 (PTA-4428), Abgenix 4.7.1 (PTA-4429), Abgenix 4.4.1 (PTA-4556), Abgenix 4.177.3 (PTA-4557), Abgenix 4.16.1 (PTA-4357), Abgenix 4.22.3 (PTA-4358), Abgenix 4.28.3 (PTA-4359), Abgenix 4.40.2 (PTA-4360), Abgenix 4.48.3 (PTA-4361), Abgenix 4.49.1 (PTA-4362), Abgenix 4.209.3 (PTA-4365), Abgenix 4.219.3 (PTA-4366), Abgenix 4.288.1 (PTA-4367), Abgenix 4.333.1 (PTA-4368), Abgenix 4.54.1 (PTA-4363), Abgenix 4.153.1 (PTA-4388), Abgenix 4.232.3 (PTA-4389), Abgenix 4.292.3 (PTA-4390), Abgenix 4.304.1 (PTA-4391), Abgenix 4.78.1 (PTA-4652), and Abgenix 4.152.1 (PTA-4653).
85. The isolated antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment thereof binds to a conformational epitope.
86. The isolated monoclonal antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody or antigen-binding fragment thereof is internalized into a cell with the prostate specific membrane antigen.
AMENDED SHEET (ARTICLE 19J 152
87. A hybridoma cell line that produces an antibody selected from the group consisting of PSMA 3.7, PSMA 3.8, PSMA 3.9, PSMA 3.11, PSMA 5.4, PSMA 7.1, PSMA 7.3, PSMA 10.3, PSMA 1.8.3, PSMA A3.1.3, PSMA A3.3.1, Abgenix 4.248.2, Abgenix 4.360.3, Abgenix 4.7.1, Abgenix 4.4.1, Abgenix 4.177.3, Abgenix 4.16.1, Abgenix 4.22.3, Abgenix 4.28.3, Abgenix 4.40.2, Abgenix 4.48.3, Abgenix 4.49.1, Abgenix 4.209.3, Abgenix 4.219.3, Abgenix 4.288.1, Abgenix 4.333.1, Abgenix 4.54.1, Abgenix 4.153.1, Abgenix 4.232.3, Abgenix 4.292.3, Abgenix 4.304.1 , Abgenix 4.78.1 and Abgenix 4.152.1.
88. The hybridoma cell line of claim 87, wherein the hybridoma cell line is selected from the group consisting of PSMA 3.7 (PTA-3257), PSMA 3.8, PSMA 3.9 (PTA-3258), PSMA 3.11 (PTA-3269), PSMA 5.4 (PTA-3268), PSMA 7.1 (PTA-3292), PSMA 7.3 (PTA-3293), PSMA 10.3 (PTA-3247) , PSMA 1.8.3 (PTA-3906), PSMA A3.1.3 (PTA-3904), PSMA A3.3.1 (PTA-3905), Abgenix 4.248.2 (PTA-4427), Abgenix 4.360.3 (PTA-4428), Abgenix 4.7.1 (PTA-4429), Abgenix 4.4.1 (PTA-4556), Abgenix 4.177.3 (PTA-4557), Abgenix 4.16.1 (PTA-4357), Abgenix 4.22.3 (PTA-4358), Abgenix 4.28.3 (PTA-4359), Abgenix 4.40.2 (PTA-4360), Abgenix 4.48.3 (PTA-4361), Abgenix 4.49.1 (PTA-4362), Abgenix 4.209.3 (PTA-4365), Abgenix 4.219.3 (PTA-4366), Abgenix 4.288.1 (PTA-4367), Abgenix 4.333.1 (PTA-4368), Abgenix 4.54.1 (PTA-4363), Abgenix 4.153.1 (PTA-4388), Abgenix 4.232.3 (PTA-4389), Abgenix 4.292.3 (PTA-4390), Abgenix 4.304.1 (PTA-4391), Abgenix 4.78.1 (PTA-4652), and Abgenix 4.152.1(PTA-4653).
89. A composition comprising: an antibody or antigen-binding fragment thereof according to any one of claims 1-34 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
90. The composition of claim 89, further comprising an antitumor agent, an immunostimulatory agent, an immunomodulator, or a combination thereof.
91. The composition of claim 90, wherein the antitumor agent is a cytotoxic agent, an agent that acts on tumor neovasculature, or a combination thereof. 153
92. The composition of claim 90, wherein the immunomodulator is α-interferon, γ-interferon, tumor necrosis factor-α or a combination thereof.
93. The composition of claim 90, wherein the immunostimulatory agent is interleu in-2, immunostimulatory oligonucleotides, or a combination thereof.
94. A composition comprising: a combination of two or more antibodies or antigen-binding fragments thereof according to any one of claims 1-34 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
95. The composition of claim 94, further comprising an antitumor agent, an immunostimulatory agent, an immunomodulator, or a combination thereof.
96. The composition of claim 95, wherein the antitumor agent is a cytotoxic agent, an agent that acts on tumor neovasculature, or a combination thereof.
97. The composition of claim 95, wherein the immunomodulator is α-interferon, γ-interferon, tumor necrosis factor-α or a combination thereof.
98. The composition of claim 95, wherein the immunostimulatory agent is interleukin-2, immunostimulatory oligonucleotides, or a combination thereof.
99. The isolated antibody or antigen-binding fragment thereof of claim 1, bound to a label.
100. The isolated monoclonal antibody or antigen-binding fragment thereof according to claim 99, wherein the label is selected from the group consisting of a fluorescent label, an enzyme label, a radioactive label, a nuclear magnetic resonance active label, a luminescent label, and a chromophore label.
101. A composition comprising: an antibody or antigen-binding fragment thereof according to claim 99 and 154
a pharmaceutically acceptable carrier, excipient, or stabilizer.
102. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof specifically binds cell-surface PSMA and/or rsPSMA with a binding affinity of about 1 X 10"9M or less.
103. The isolated antibody or antigen-binding fragment thereof of claim 102, wherein the binding affinity is about 1 X 10"10M or less.
104. The isolated antibody or antigen-binding fragment thereof of claim 103, wherein the binding affinity is about 1 X 10"' !M or less.
105. The isolated antibody or antigen-binding fragment thereof of claim 102, wherein the binding affinity is less than about 5 X 10"10M.
106. The isolated antibody or antigen-binding fragment thereof of claim 1, bound to at least one therapeutic moiety .
107. The isolated antibody or antigen-binding fragment thereof of claim 106, wherein the antibody or antigen-binding fragment thereof mediates specific cell killing of PSMA- expressing cells with an IC50 of less than about 1 X 10"10M.
108. The isolated antibody or antigen-binding fragment thereof of claim 107, wherein the IC50 is less than about 1 X 10"nM.
109. The isolated antibody or antigen-binding fragment thereof of claim 108, wherein the IC50 is less than about 1 X 10"I2M.
1 10. The isolated antibody or antigen-binding fragment thereof of claim 107, wherein the IC50 is less than about 1.5 X 10"1 ' M.
111. The isolated antibody or antigen-binding fragment thereof of claim 106, wherein the therapeutic moiety is a drug.
112. The isolated antibody or antigen-binding fragment thereof of claim 106, wherein the therapeutic moiety is a replication selective virus.
113. The isolated antibody or antigen-binding fragment thereof of claim 1 11, wherein the drug is a cytotoxic drug.
1 14. The isolated antibody or antigen-binding fragment thereof of claim 113, wherein the cytotoxic drug is selected from the group consisting of: calicheamicin, esperamicin, methotrexate, doxorubicin, melphalan, chlorambucil, ARA-C, vindesine, mitomycin C, cis- platinum, etoposide, bleomycin, 5-fluorouracil, estramustine, vincristine, etoposide, doxorubicin, paclitaxel, docetaxel, dolastatin 10, auristatin E and auristatin PHE.
1 15. The isolated antibody or antigen-binding fragment thereof of claim 106, wherein the therapeutic moiety is a toxin or a fragment thereof.
116. The isolated antibody or antigen-binding fragment thereof of claim 106, wherein the therapeutic moiety is an enzyme or a fragment thereof.
117. The isolated antibody or antigen-binding fragment thereof of claim 106, wherein the therapeutic moiety is an immunostimulatory or immunomodulating agent.
118. The isolated antibody or antigen-binding fragment thereof of claim 117, wherein the immunostimulatory or immunomodulating agent is selected from the group consisting of: a cytokine, chemokine and adjuvant.
119. A composition comprising: the antibody or antigen-binding fragment of claim 106 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
120. The isolated antibody or antigen-binding fragment thereof of 1, bound to a radioisotope. 156
121. The isolated antibody or antigen-binding fragment thereof according to claim 120, wherein the radioisotope emits α radiations.
122. The isolated antibody or antigen-binding fragment thereof according to claim 120, wherein the radioisotope emits β radiations.
123. The isolated antibody or antigen-binding fragment thereof according to claim 120, wherein the radioisotope emits γ radiations.
124. The isolated antibody or antigen-binding fragment thereof according to claim 120, wherein the radioisotope is selected from the group consisting of 225Ac, 21 ,At, 212Bi, 213Bi, , 86Rh, , 88Rh, ,77Lu, 90Y, ,3,I, 67Cu, 125I, ,231, 77Br, 153Sm, 166Ho, 64Cu, 212Pb, 224Ra and 223Ra.
125. A composition comprising the isolated antibody or antigen-binding fragment thereof of claim 120 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
126. A kit for detecting prostate cancer for diagnosis, prognosis or monitoring comprising: the isolated labeled antibody or antigen-binding fragment thereof of claim 99, and one or more compounds for detecting the label.
127. A kit according to claim 126, wherein the label is selected from the group consisting of a fluorescent label, an enzyme label, a radioactive label, a nuclear magnetic resonance active label, a luminescent label, and a chromophore label.
128. The isolated antibody or antigen-binding fragment thereof of any of claims 1, 99, 106 or 120 packaged in lyophilized form.
129. The isolated antibody or antigen-binding fragment thereof of any of claims 1 , 99, 106 or 120 packaged in an aqueous medium.
139. An isolated antibody or an antigen-binding fragment thereof which specifically binds to an epitope on prostate specific membrane antigen (PSMA) defined by an antibody selected from the group consisting of PSMA 3.7, PSMA 3.8, PSMA 3.9, PSMA 3.11, PSMA 5.4, 157
PSMA 7.1, PSMA 7.3, PSMA 10.3, PSMA 1.8.3, PSMA B3.1.3, PSMA B3.3.1, Abgenix
4.248.2, Abgenix 4.360.3, Abgenix 4.7.1, Abgenix 4.4.1, Abgenix 4.177.3, Abgenix 4.16.1 , Abgenix 4.22.3, Abgenix 4.28.3, Abgenix 4.40.2, Abgenix 4.48.3, Abgenix 4.49.1, Abgenix
4.209.3, Abgenix 4.219.3, Abgenix 4.288.1, Abgenix 4.333.1, Abgenix 4.54.1 , Abgenix 4.153.1, Abgenix 4.232.3, Abgenix 4.292.3, Abgenix 4.304.1, Abgenix 4.78.1, Abgenix
4.152.1, and antibodies comprising:
(a) a heavy chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as SEQ ID NOs: 2-7, and (b) a light chain encoded by a nucleic acid molecule comprising the coding region or regions of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as SEQ ID NOs: 8-13.
131. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of PSMA 3.7, PSMA 3.8, PSMA 3.9, PSMA 3.1 1, PSMA 5.4, PSMA 7.1, PSMA 7.3, PSMA 10.3, PSMA 1.8.3, PSMA B3.1.3, PSMA B3.3.1, Abgenix 4.248.2, Abgenix 4.360.3, Abgenix 4.7.1, Abgenix 4.4.1, Abgenix 4.177.3, Abgenix 4.16.1, Abgenix 4.22.3, Abgenix 4.28.3, Abgenix 4.40.2, Abgenix 4.48.3, Abgenix 4.49.1, Abgenix 4.209.3, Abgenix 4.219.3, Abgenix 4.288.1, Abgenix 4.333.1, Abgenix 4.54.1, Abgenix 4.153.1 , Abgenix 4.232.3, Abgenix 4.292.3, Abgenix 4.304.1, Abgenix 4.78.1, Abgenix 4.152.1 and antigen- binding fragments thereof.
132. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of antibodies comprising:
(a) a heavy chain encoded by a nucleic acid molecule comprising the heavy chain coding region or regions of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as SEQ ID NOs: 2-7, and (b) a light chain encoded by a nucleic acid molecule comprising the light chain coding region or regions of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as SEQ ID NOs: 8-13, and antigen-binding fragments thereof. 03/034903
158
133. An isolated antibody which specifically binds to an epitope on prostate specific membrane antigen, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 90% identical to the nucleotide sequence encoding the antibody of claim 132.
134. The isolated antibody of claim 133, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 95% identical.
135. The isolated antibody of claim 133, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 97% identical.
136. The isolated antibody of claim 133, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 98% identical.
137. The isolated antibody of claim 133, wherein the antibody is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least about 99% identical.
138. An antigen-binding fragment of the isolated antibody of claim 132, comprising: (a) a heavy chain variable region encoded by a nucleic acid molecule comprising the coding regions or regions of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as: SEQ ID NOs: 14, 18, 22, 26 and 30, and
(b) a light chain variable region encoded by a nucleic acid molecule comprising the coding region or region of a nucleotide sequence selected from the group consisting of nucleotide sequences set forth as: SEQ ID NOs: 16, 20, 24, 28 and 32.
139. The antigen-binding fragment of the isolated antibody of claim 132, comprising:
(a) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of amino acid sequences set forth as: SEQ ID NOs: 1 , 19, 23, 27 and 31, and
(b) a light chain variable region comprising an amino acid sequence selected from the group consisting of nucleotide sequences set forth as: SEQ ID NOs: 17, 21, 25, 29 and 33. 159
140. An isolated antigen-binding fragment which comprises a CDR of the antigen-binding fragment according to claim 138 or claim 139.
141. The isolated antigen-binding fragment of claim 140, wherein the CDR is CDR3.
142. An expression vector comprising an isolated nucleic acid molecule encoding the isolated antibody or antigen-binding fragment of any one of claims 130-138.
143. A host cell transformed or transfected by the expression vector of claim 142.
144. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody or antigen-binding fragment thereof is selected for its ability to bind live cells.
145. The isolated antibody or antigen-binding fragment thereof of claim 144 , wherein the cell is a tumor cell.
146. The isolated antibody or antigen-binding fragment thereof of claim 145, wherein the tumor cell is a prostate tumor cell.
147. The isolated antibody or antigen-binding fragment thereof of claim 146, wherein the tumor cell is a LNCaP cell.
148. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody or antigen-binding fragment thereof mediates cytolysis of cells expressing PSMA.
149. The isolated antibody or antigen-binding fragment thereof of claim 148 wherein cytolysis of cells expressing PSMA is mediated by effector cells.
150. The isolated antibody or antigen-binding fragment thereof of claim 148 wherein cytolysis of cells expressing PSMA is complement mediated in the presence of effector cells. 03/034903
160
151. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody or antigen-binding fragment thereof inhibits the growth of cells expressing PSMA.
152. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody or antigen-binding fragment thereof does not require cell lysis to bind to the epitope on PSMA.
153. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgAsec, IgD, IgE or has immunoglobulin constant and/or variable domain of IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgAsec, IgA or IgE.
154. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody is a recombinant antibody.
155. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody is a polyclonal antibody.
156. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody is a monoclonal antibody.
157. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody is a humanized antibody.
158. The isolated antibody or antigen-binding fragment thereof according to claim 157, wherein said antibody is a monoclonal antibody.
159. The isolated antibody or antigen-binding fragment thereof according to claim 157, wherein said antibody is a polyclonal antibody. 161
160. The isolated antibody or antigen-binding fragment thereof according to claim 157, wherein said antibody is a mixture of monoclonal and/or polyclonal antibodies.
161. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody is a chimeric antibody.
162. The isolated antibody or antigen-binding fragment thereof according to claim 161, wherein said antibody is a monoclonal antibody.
163. The isolated antibody or antigen-binding fragment thereof according to claim 161, wherein said antibody is a polyclonal antibody.
164. The isolated antibody or antigen-binding fragment thereof according to claim 161, wherein said antibody is a mixture of monoclonal and/or polyclonal antibodies.
165. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody is a human antibody.
166. The isolated antibody or antigen-binding fragment thereof according to claim 165, wherein said antibody is a monoclonal antibody.
167. The isolated antibody or antigen-binding fragment thereof according to claim 165, wherein said antibody is a polyclonal antibody.
168. The isolated antibody or antigen-binding fragment thereof according to claim 165, wherein said antibody is a mixture of monoclonal and/or polyclonal antibodies.
169. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein said antibody is a bispecific or multispecific antibody.
170. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein the isolated antigen-binding fragment is selected from the group consisting of a Fab fragment, a F(ab')2 fragment, and a Fv fragment CDR3. 162
171. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein the antibody is a monoclonal antibody produced by a hybridoma cell line selected from the group consisting of PSMA 3.7 (PTA-3257), PSMA 3.8, PSMA 3.9 (PTA-3258), PSMA 3.11 (PTA-3269), PSMA 5.4 (PTA-3268), PSMA 7.1 (PTA-3292), PSMA 7.3 (PTA- 3293), PSMA 10.3 (PTA-3247) , PSMA 1.8.3 (PTA-3906), PSMA B3.1.3 (PTA-3904), PSMA B3.3.1 (PTA-3905), Abgenix 4.248.2 (PTA-4427), Abgenix 4.360.3 (PTA-4428), Abgen x 4.7.1 (PTA-4429), Abgenix 4.4.1 (PTA-4556), Abgenix 4.177.3 (PTA-4557), Abgen x 4.16.1 (PTA-4357), Abgenix 4.22.3 (PTA-4358), Abgenix 4.28.3 (PTA-4359), Abgen x 4.40.2 (PTA-4360), Abgenix 4.48.3 (PTA-4361), Abgenix 4.49.1 (PTA-4362), Abgen x 4.209.3 (PTA-4365), Abgenix 4.219.3 (PTA-4366), Abgenix 4.288.1 (PTA-4367), Abgen x 4.333.1 (PTA-4368), Abgenix 4.54.1 (PTA-4363), Abgenix 4.153.1 (PTA-4388), Abgen x 4.232.3 (PTA-4389), Abgenix 4.292.3 (PTA-4390), Abgenix 4.304.1 (PTA-4391), Abgen x 4.78.1 (PTA-4652), and Abgenix 4.152.1(PTA-4653).
172. The isolated antibody or antigen-binding fragment thereof according to claim 130, wherein the antibody or antigen-binding fragment thereof binds to a conformational epitope.
173. The isolated monoclonal antibody or antigen-binding fragment thereof according to claim 130, wherein the antibody or antigen-binding fragment thereof is internalized into a cell with the prostate specific membrane antigen.
174. A hybridoma cell line that produces an antibody selected from the group consisting of PSMA 3.7, PSMA 3.8, PSMA 3.9, PSMA 3.11, PSMA 5.4, PSMA 7.1, PSMA 7.3, PSMA 10.3, PSMA 1.8.3, PSMA B3.1.3, PSMA B3.3.1 , Abgenix 4.248.2, Abgenix 4.360.3,
Abgenix 4.7.1, Abgenix 4.4.1, Abgenix 4.177.3, Abgenix 4.16.1 , Abgenix 4.22.3, Abgenix 4.28.3, Abgenix 4.40.2, Abgenix 4.48.3, Abgenix 4.49.1, Abgenix 4.209.3, Abgenix 4.219.3, Abgenix 4.288.1, Abgenix 4.333.1, Abgenix 4.54.1, Abgenix 4.153.1, Abgenix 4.232.3, Abgenix 4.292.3, Abgenix 4.304.1, Abgenix 4.78.1 and Abgenix 4.152.1.
175. The hybridoma cell line of claim 174, wherein the hybridoma cell line is selected from the group consisting of PSMA 3.7 (PTA-3257), PSMA 3.8, PSMA 3.9 (PTA-3258), PSMA 3.11 (PTA-3269), PSMA 5.4 (PTA-3268), PSMA 7.1 (PTA-3292), PSMA 7.3 (PTA- 163
3293), PSMA 10.3 (PTA-3247) , PSMA 1.8.3 (PTA-3906), PSMA B3.1.3 (PTA-3904), PSMA B3.3.1 (PTA-3905), Abgenix 4.248.2 (PTA-4427), Abgenix 4.360.3 (PTA-4428), Abgenix 4.7.1 (PTA-4429), Abgenix 4.4.1 (PTA-4556), Abgenix 4.177.3 (PTA-4557), Abgenix 4.16.1 (PTA-4357), Abgenix 4.22.3 (PTA-4358), Abgenix 4.28.3 (PTA-4359), Abgenix 4.40.2 (PTA-4360), Abgenix 4.48.3 (PTA-4361), Abgenix 4.49.1 (PTA-4362), Abgenix 4.209.3 (PTA-4365), Abgenix 4.219.3 (PTA-4366), Abgenix 4.288.1 (PTA-4367), Abgenix 4.333.1 (PTA-4368), Abgenix 4.54.1 (PTA-4363), Abgenix 4.153.1 (PTA-4388), Abgenix 4.232.3 (PTA-4389), Abgenix 4.292.3 (PTA-4390), Abgenix 4.304.1 (PTA-4391), Abgenix 4.78.1 (PTA-4652), and Abgenix 4.152.1(PTA-4653).
176. A composition comprising: an antibody or antigen-binding fragment thereof according to any one of claims 130- 141 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
177. The composition of claim 176, further comprising an antitumor agent, an immunostimulatory agent, an immunomodulator, or a combination thereof.
178. The composition of claim 177, wherein the antitumor agent is a cytotoxic agent, an agent that acts on tumor neovasculature, or a combination thereof.
179. The composition of claim 177, wherein the immunomodulator is α-interferon, γ- interferon, tumor necrosis factor-α or a combination thereof.
180. The composition of claim 177, wherein the immunostimulatory agent is interleukin-2, immunostimulatory oligonucleotides, or a combination thereof.
181. A composition comprising: a combination of two or more antibodies or antigen-binding fragments thereof according to any one of claims 130-141 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
182. The composition of claim 181, further comprising an antitumor agent, an immunostimulatory agent, an immunomodulator, or a combination thereof. 164
183. The composition of claim 182, wherein the antitumor agent is a cytotoxic agent, an agent that acts on tumor neovasculature, or a combination thereof.
184. The composition of claim 182, wherein the immunomodulator is α-interferon, γ- interferon, tumor necrosis factor-α or a combination thereof.
185. The composition of claim 182, wherein the immunostimulatory agent is interleukin-2, immunostimulatory oligonucleotides, or a combination thereof.
186. The isolated antibody or antigen-binding fragment thereof of claim 130, bound to a label.
187. The isolated monoclonal antibody or antigen-binding fragment thereof according to claim 186, wherein the label is selected from the group consisting of a fluorescent label, an enzyme label, a radioactive label, a nuclear magnetic resonance active label, a luminescent label, and a chromophore label.
188. A composition comprising: an antibody or antigen-binding fragment thereof according to claim 186 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
189. The isolated antibody or antigen-binding fragment thereof of claim 130, wherein the antibody or antigen-binding fragment thereof specifically binds cell-surface PSMA and/or rsPSMA with a binding affinity of about 1 X 10"9M or less.
190. The isolated antibody or antigen-binding fragment thereof of claim 189, wherein the binding affinity is about 1 X 10'10M or less.
191. The isolated antibody or antigen-binding fragment thereof of claim 189, wherein the binding affinity is about 1 X 10"" M or less. 165
192. The isolated antibody or antigen-binding fragment thereof of claim 189, wherein the binding affinity is less than about 5 X 10"I0M.
193. The isolated antibody or antigen-binding fragment thereof of claim 130, bound to at least one therapeutic moiety .
194 The isolated antibody or antigen-binding fragment thereof of claim 193, wherein the antibody or antigen-binding fragment thereof mediates specific cell killing of PSMA- expressing cells with an IC50 of less than about 1 X 10"' °M.
195. The isolated antibody or antigen-binding fragment thereof of claim 194, wherein the IC50 is less than about 1 X 10"nM.
196. The isolated antibody or antigen-binding fragment thereof of claim 195, wherein the ICso is less than about 1 X 10"' 2M.
197. The isolated antibody or antigen-binding fragment thereof of claim 194, wherein the IC50 is less than about 1.5 X 10'πM.
198. The isolated antibody or antigen-binding fragment thereof of claim 193, wherein the therapeutic moiety is a drug.
199. The isolated antibody or antigen-binding fragment thereof of claim 193, wherein the therapeutic moiety is a replication-selective virus.
200. The isolated antibody or antigen-binding fragment thereof of claim 198, wherein the drug is a cytotoxic drug.
201. The isolated antibody or antigen-binding fragment thereof of claim 200, wherein the cytotoxic drug is selected from the group consisting of: calicheamicin, esperamicin, methotrexate, doxorubicin, melphalan, chlorambucil, ARA-C, vindesine, mitomycin C, cis- platinum, etoposide, bleomycin, 5-fluorouracil, estramustine, vincristine, etoposide, doxorubicin, paclitaxel, docetaxel, dolastatin 10, auristatin E and auristatin PHE. 166
202. The isolated antibody or antigen-binding fragment thereof of claim 193, wherein the therapeutic moiety is a toxin or a fragment thereof.
203. The isolated antibody or antigen-binding fragment thereof of claim 193, wherein the therapeutic moiety is an enzyme or a fragment thereof.
204. The isolated antibody or antigen-binding fragment thereof of claim 193, wherein the therapeutic moiety is an immunostimulatory or immunomodulating agent.
205. The isolated antibody or antigen-binding fragment thereof of claim 204, wherein the immunostimulatory or immunomodulating agent is selected from the group consisting of: a cytokine, chemokine and adjuvant.
206. A composition comprising: the antibody or antigen-binding fragment of claim 193 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
207. The isolated antibody or antigen-binding fragment thereof of 130, bound to a radioisotope.
208. The isolated antibody or antigen-binding fragment thereof according to claim 207, wherein the radioisotope emits α radiations.
209. The isolated antibody or antigen-binding fragment thereof according to claim 207, wherein the radioisotope emits β radiations.
210. The isolated antibody or antigen-binding fragment thereof according to claim 207, wherein the radioisotope emits γ radiations.
21 1. The isolated antibody or antigen-binding fragment thereof according to claim 207,
99 S 91 1 17 91 "^ wherein the radioisotope is selected from the group consisting of Ac, At, Bi, Bi, l 86Rh, 188Rh, 177Lu, 90Y, 13,1, 67Cu, ,25I, l231, 77Br, 153Sm, 166Ho, 64Cu, 212Pb, 224Ra and 23Ra. 167
212. A composition comprising the isolated antibody or antigen-binding fragment thereof of claim 207 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
213. A kit for detecting prostate cancer for diagnosis, prognosis or monitoring comprising: the isolated labeled antibody or antigen-binding fragment thereof of claim 186, and one or more compounds for detecting the label.
214. A kit according to claim 213, wherein the label is selected from the group consisting of a fluorescent label, an enzyme label, a radioactive label, a nuclear magnetic resonance active label, a luminescent label, and a chromophore label.
215. The isolated antibody or antigen-binding fragment thereof of any of claims 130, 186, 193 or 207 packaged in lyophilized form.
216. The isolated antibody or antigen-binding fragment thereof of any of claims 130, 186, 193 or 207 packaged in an aqueous medium.
217. A method for detecting the presence of PSMA, or a cell expressing PSMA, in a sample comprising: contacting the sample with an antibody or antigen-binding fragment thereof according to claim 1 or 130 for a time sufficient to allow the formation of a complex between the antibody or antigen-binding fragment thereof and PSMA, and detecting the PSMA-antibody complex or PSMA-antigen-binding fragment complex, wherein the presence of a complex in the sample is indicative of the presence in the sample of PSMA or a cell expressing PSMA.
218. A method for diagnosing a PSMA-mediated disease in a subject comprising: administering to a subject suspected of having or previously diagnosed with PSMA- mediated disease an isolated amount of an antibody or antigen-binding fragment thereof according to claim 1 or 130, allowing the formation of a complex between the antibody or antigen-binding fragment thereof and PSMA, 168
detecting the formation of the PSMA-antibody complex or PSMA-antigen-binding fragment complex to the target epitope, wherein the presence of a complex in the subject suspected of having or previously diagnosed with PSMA-mediated disease is indicative of the presence of a PSMA-mediated disease.
219. The method of claim 218 wherein the PSMA-mediated disease is prostate cancer.
220. The method of claim 218 wherein the PSMA-mediated disease is a non-prostate cancer.
221. The method of claim 220 wherein the non-prostate cancer is selected from the group consisting of bladder cancer including transitional cell carcinoma; pancreatic cancer including pancreatic duct carcinoma; lung cancer including non-small cell lung carcinoma; kidney cancer including conventional renal cell carcinoma; sarcoma including soft tissue sarcoma; breast cancer including breast carcinoma; brain cancer including glioblastoma multiforme; neuroendocrine carcinoma; colon cancer including colonic carcinoma; testicular cancer including testicular embryonal carcinoma; and melanoma including malignant melanoma.
221. The method of claim 217 or claim 218 wherein the antibody or antigen-binding fragment thereof is labeled.
223. The method of claim 217 or claim 218 wherein a second antibody is administered to detect the first antibody or antigen-binding fragment thereof.
224. A method for assessing the prognosis of a subject with a PSMA-mediated disease: administering to a subject suspected of having or previously diagnosed with PSMA- mediated disease an effective amount of an antibody or antigen-binding fragment thereof according to claim 1 or 130, allowing the formation of a complex between the antibody or antigen-binding fragment thereof and PSMA, detecting the formation of the complex to the target epitope, 169
wherein the amount of the complex in the subject suspected of having or previously diagnosed with PSMA-mediated disease is indicative of the prognosis.
225. A method for assessing the effectiveness of a treatment of a subject with a PSMA- mediated disease: administering to a subject suspected treated for a PSMA-mediated disease an effective amount of an antibody or antigen-binding fragment thereof according to claim 1 or 130, allowing the formation of a complex between the antibody or antigen-binding fragment thereof and PSMA, detecting the formation of the complex to the target epitope, wherein the amount of the complex in the subject suspected of having or previously diagnosed with PSMA-mediated disease is indicative of the effectiveness of the treatment.
226. The method of claim 224 or claim 225 wherein the PSMA-mediated disease is prostate cancer.
227. The method of claim 224 or claim 225 wherein the PSMA-mediated disease is a non- prostate cancer.
228. The method of claim 227 wherein the non-prostate cancer is selected from the group consisting of bladder cancer including transitional cell carcinoma; pancreatic cancer . including pancreatic duct carcinoma; lung cancer including non-small cell lung carcinoma; kidney cancer including conventional renal cell carcinoma; sarcoma including soft tissue sarcoma; breast cancer including breast carcinoma; brain cancer including glioblastoma multiforme; neuroendocrine carcinoma; colon cancer including colonic carcinoma; testicular cancer including testicular embryonal carcinoma; and melanoma including malignant melanoma.
229. The method of claim 224 or claim 225 wherein the antibody or antigen-binding fragment thereof is labeled.
230. The method of claim 224 or claim 225 wherein a second antibody is administered to detect the first antibody or antigen-binding fragment thereof. 170
231. A method for inhibiting the growth of a cell expressing PSMA comprising: contacting a cell expressing PSMA with an amount of an antibody or antigen-binding fragment thereof according to claim 1 or 130 which specifically binds to an extracellular domain of PSMA effective to inhibit the growth of the cell expressing PSMA.
232. A method for inducing cytolysis of a cell expressing PSMA comprising: contacting a cell expressing PSMA with an amount of an antibody or antigen-binding fragment thereof according to claim 1 or 130 which specifically binds to an extracellular domain of PSMA effective to induce cytolysis of the cell expressing PSMA.
233. The method of claim 232 wherein the cytolysis occurs in the presence of an effector cell.
234. The method of claim 232 wherein the cytolysis is complement mediated.
235. A method for treating or preventing a PSMA-mediated disease comprising: administering to a subject having a PSMA-mediated disease or at risk of having a PSMA- mediated disease an effective amount of an antibody or antigen-binding fragment thereof according to claim 1 or 130 to treat or prevent the PSMA-mediated disease.
236. The method of claim 235 wherein the PSMA-mediated disease is a cancer.
237. The method for claim 236 wherein the cancer is a prostate cancer.
238. The method for claim 236 wherein the cancer is a non-prostate cancer.
239. A method for treating or preventing a PSMA-mediated disease comprising: administering to a subject having a PSMA-mediated disease or at risk of having a PSMA-mediated disease an amount of an antibody or antigen-binding fragment thereof according to claim 1 or 130 effective to treat or prevent the PSMA-mediated disease.
240. The method of claim 239, wherein the PSMA-mediated disease is a cancer. 171
241. The method of claim 240, wherein the cancer is prostate cancer.
242. The method of claim 240, wherein the cancer is a non-prostate cancer.
243. The method of claim 242, wherein the non-prostate cancer is selected from the group consisting of: bladder cancer including transitional cell carcinoma; pancreatic cancer including pancreatic duct carcinoma; lung cancer including non-small cell lung carcinoma; kidney cancer including conventional renal cell carcinoma; sarcoma including soft tissue sarcoma; breast cancer including breast carcinoma; brain cancer including glioblastoma multiforme; neuroendocrine carcinoma; colon cancer including colonic carcinoma; testicular cancer including testicular embryonal carcinoma; and melanoma including malignant melanoma.
244. The method of claim 239, further comprising administering another therapeutic agent to treat or prevent the PSMA-mediated disease at any time before, during or after the administration of the antibody or antigen-binding fragment thereof.
245. The method of claim 244, wherein the therapeutic agent is a vaccine.
246. The method of claim 245, wherein the vaccine immunizes the subject against PSMA.
247. The method of claim 244, wherein the antibody or antigen-binding fragment thereof is bound to at least one therapeutic moiety.
248. The method of claim 247, wherein the therapeutic moiety is a cytotoxic drug, a drug which acts on the tumor neovasculature and combinations thereof.
249. The method of claim 248, wherein the cytotoxic drug is selected from the group consisting of: calicheamicin, esperamicin, methotrexate, doxorubicin, melphalan, chlorambucil, ARA-C, vindesine, mitomycin C, cis-platinum, etoposide, bleomycin, 5- fluorouracil, estramustine, vincristine, etoposide, doxorubicin, paclitaxel, docetaxel, dolastatin 10, auristatin E and auristatin PHE. 172
250. The method of claim 247, wherein the antibody or antigen-binding fragment thereof is bound to a radioisotope, wherein the radiations emitted by the radioisotope is selected from the group consisting of , β and γ radiations.
251. The method of claim 250, wherein the radioisotope is selected from the group consisting of 225Ac, 211At, 2,2Bi, 213Bi, , 86Rh, ,88Rh, 177Lu, 90Y, l3!I, 67Cu, l25I, 123I, 77Br, 153Sm, 166Ho, 64Cu, 12Pb, 224Ra and 223Ra.
252. A method for inhibiting folate hydrolase activity comprising: contacting a folate hydrolase polypeptide with an amount of isolated antibody or antigen-binding fragment thereof according to claim 1 or claim 130 under conditions wherein the isolated antibody or antigen-binding fragment thereof inhibits the folate hydrolase activity.
253. The method of claim 252 wherein the folate hydrolase polypeptide is isolated.
254. The method of claim 252 wherein the folate hydrolase polypeptide is contained in a sample selected from the group consisting of a cell, a cell homogenate, a tissue, or a tissue homogenate.
255. The method of claim 252 wherein the folate hydrolase polypeptide is contained in an organism.
256. The method of claim 255 wherein the organism is an animal.
257. The method of claim 256 wherein the animal is a mammal.
258. A method for enhancing folate hydrolase activity comprising: contacting a folate hydrolase polypeptide with an amount of isolated antibody or antigen-binding fragment thereof according to claim 1 or claim 130 under conditions wherein the isolated antibody or antigen-binding fragment thereof enhances the folate hydrolase activity. 173
259. The method of claim 258 wherein the folate hydrolase polypeptide is isolated.
260. The method of claim 258 wherein the folate hydrolase polypeptide is contained in a sample selected from the group consisting of a cell, a cell homogenate, a tissue, or a tissue homogenate.
261. The method of claim 258 wherein the folate hydrolase polypeptide is contained in an organism.
262. The method of claim 261 wherein the organism is an animal.
263. The method of claim 262 wherein the animal is a mammal.
264. A method for inhibiting N-acetylated α-linked acidic dipeptidase (NAALADase) activity comprising: contacting a NAALADase polypeptide with an amount of an isolated antibody or antigen-binding fragment thereof according to claim 1 or claim 130 under conditions wherein the isolated antibody or antigen-binding fragment thereof inhibits NAALADase activity.
265. The method for claim 264 wherein the NAALADase polypeptide is isolated.
266. The method for claim 264 wherein the NAALADase polypeptide is contained in a sample selected from the group consisting of a cell, a cell homogenate, a tissue, or a tissue homogenate.
267. The method for claim 264 wherein the NAALADase polypeptide is contained in an organism.
268. The method for claim 267 wherein the organism is an animal.
269. The method for claim 268 wherein the animal is a mammal.
AMENDED SHEET (ARTICLE 1$ 174
270. A method for enhancing N-acetylated α-linked acidic dipeptidase (NAALADase) activity comprising: contacting a NAALADase polypeptide with an amount of an isolated antibody or antigen-binding fragment thereof according to claim 1 or claim 130 under conditions wherein the isolated antibody or antigen-binding fragment thereof enhances NAALADase activity.
271. The method for claim 270 wherein the NAALADase polypeptide is isolated.
272. The method for claim 270 wherein the NAALADase polypeptide is contained in a sample selected from the group consisting of a cell, a cell homogenate, a tissue, or a tissue homogenate.
273. The method for claim 270 wherein the NAALADase polypeptide is contained in an organism.
274. The method for claim 273 wherein the organism is an animal.
275. The method for claim 274 wherein the animal is a mammal.
276. A method for inhibiting dipeptidyl dipeptidase IV activity comprising: contacting a dipeptidyl dipeptidase IV polypeptide with an amount of an isolated antibody or antigen-binding fragment thereof according to claim 1 or claim 130 under conditions wherein the isolated antibody or antigen-binding fragment thereof inhibits dipeptidyl dipeptidase IV activity.
277. The method for claim 276 wherein the dipeptidyl dipeptidase IV polypeptide is isolated.
278. The method for claim 276 wherein the dipeptidyl dipeptidase IV polypeptide is contained in a sample selected from the group consisting of a cell, a cell homogenate, a tissue, or a tissue homogenate. 175
279. The method for claim 276 wherein the dipeptidyl dipeptidase IV polypeptide is contained in an organism.
280. The method for claim 279 wherein the organism is an animal.
281. The method for claim 280 wherein the animal is a mammal.
282. A method for inhibiting dipeptidyl dipeptidase IV activity comprising: contacting a dipeptidyl dipeptidase IV polypeptide with an amount of an isolated antibody or antigen-binding fragment thereof according to claim 1 or claim 130 under conditions wherein the isolated antibody or antigen-binding fragment thereof inhibits dipeptidyl dipeptidase IV activity.
283. The method for claim 282 wherein the dipeptidyl dipeptidase IV polypeptide is isolated.
284. The method for claim 282 wherein the dipeptidyl dipeptidase IV polypeptide is contained in a sample selected from the group consisting of a cell, a cell homogenate, a tissue, or a tissue homogenate.
285. The method for claim 282 wherein the dipeptidyl dipeptidase IV polypeptide is contained in an organism.
286. ' The method for claim 285 wherein the organism is an animal.
287. The method for claim 286 wherein the animal is a mammal.
288. A method for inhibiting γ-glutamyl hydrolase activity comprising: contacting a γ-glutamyl hydrolase polypeptide with an amount of an isolated antibody or antigen-binding fragment thereof according to claim 1 or claim 130 under conditions wherein the isolated antibody or antigen-binding fragment thereof inhibits γ-glutamyl hydrolase activity.
AMENDED SHEET (ARTICLE 19)
/ 176
289. The method for claim 288 wherein the γ-glutamyl hydrolase polypeptide is isolated.
290. The method for claim 288 wherein the γ-glutamyl hydrolase polypeptide is contained in a sample selected from the group consisting of a cell, a cell homogenate, a tissue, or a tissue homogenate.
291. The method for claim 288 wherein the γ-glutamyl hydrolase polypeptide is contained in an organism.
292. The method for claim 291 wherein the organism is an animal.
293. The method for claim 292 wherein the animal is a mammal.
294. A method for inhibiting γ-glutamyl hydrolase activity comprising: contacting a γ-glutamyl hydrolase polypeptide with an amount of an isolated antibody or antigen-binding fragment thereof according to claim 1 or claim 130 under conditions wherein the isolated antibody or antigen-binding fragment thereof inhibits γ-glutamyl hydrolase activity.
295. The method for claim 294 wherein the γ-glutamyl hydrolase polypeptide is isolated.
296. The method for claim 294 wherein the γ-glutamyl hydrolase polypeptide is contained in a sample selected from the group consisting of a cell, a cell homogenate, a tissue, or a tissue homogenate.
297. The method for claim 294 wherein the γ-glutamyl hydrolase polypeptide is contained in an organism.
298. The method for claim 297 wherein the organism is an animal.
299. The method for claim 298 wherein the animal is a mammal. 177
300. A method of specific delivery of at least one therapeutic agent to PSMA-expressing cells, comprising: administering an effective amount of an antibody or antigen-binding fragment thereof according to claim 1 or 130 conjugated to the at least one therapeutic agent.
301. The method of claim 300, wherein the therapeutic agent is a nucleic acid molecule.
302. The method of claim 300, wherein the therapeutic agent is an antitumor drug.
303. The method of claim 302, wherein the antitumor drug is selected from the group consisting of: a cytotoxic drug, a drug which acts on the tumor neovasculature and combinations thereof.
304. The method of claim 303, wherein the cytotoxic drug is selected from the group consisting of: calicheamicin, esperamicin, methotrexate, doxorubicin, melphalan, chlorambucil, ARA-C, vindesine, mitomycin C, cis-platinum, etoposide, bleomycin, 5- fluorouracil, estramustine, vincristine, etoposide, doxorubicin, paclitaxel, docetaxel, dolastatin 10, auristatin E and auristatin PHE.
305. The method of claim 300, wherein the therapeutic moiety is a toxin or a fragment thereof.
306. The method of claim 300, wherein the therapeutic moiety is an enzyme or a fragment thereof.
307. The method of claim 300, wherein the therapeutic moiety is a replication-selective virus.
308. The method of claim 300, wherein the therapeutic moiety is an immunostimulatory or immunomodulating agent.
309. The method of claim 308, wherein the immunostimulatory or immunomodulating agent is selected from the group consisting of: a cytokine, chemokine and adjuvant. 178
310. An isolated antibody or antigen-binding fragment thereof that selectively binds a PSMA protein multimer.
311. The isolated antibody or antigen-binding fragment thereof of claim 310, wherein the PSMA protein multimer is a dimer.
312. The isolated antibody or antigen-binding fragment thereof of claim 31 1, wherein at least one of the PSMA proteins forming the multimer is a recombinant, soluble PSMA (rsPSMA) polypeptide.
313. The isolated antibody or antigen-binding fragment thereof of claim 312, wherein the rsPSMA polypeptide consists essentially of amino acids 44-750 of SEQ ID NO:l .
314. An isolated antibody or antigen-binding fragment thereof that selectively binds a PSMA protein multimer, wherein the isolated antibody inhibits at least one enzymatic activity of the PSMA protein multimer.
315. The isolated antibody or antigen-binding fragment thereof of claim 314, wherein the enzymatic activity is selected from the group consisting of folate hydrolase activity,
NAALADase activity, dipeptidyl dipeptidase IV activity, γ-glutamyl hydrolase activity and combinations thereof.
316. The isolated antibody or antigen-binding fragment thereof of claim 314, wherein the enzymatic activity is in the extracellular domain of the PSMA molecule.
317. The isolated antibody or antigen-binding fragment thereof of claim 314, wherein the antibody or antigen-binding fragment thereof specifically binds to an extracellular domain of PSMA.
318. An isolated antibody or antigen-binding fragment thereof that selectively binds a PSMA protein multimer, wherein the isolated antibody enhances at least one enzymatic activity of the PSMA protein multimer. 179
319. The isolated antibody or antigen-binding fragment thereof of claim 318, wherein the enzymatic activity is selected from the group consisting of folate hydrolase activity, NAALADase activity, dipeptidyl dipeptidase IV activity, γ-glutamyl hydrolase activity and combinations thereof.
320. The isolated antibody or antigen-binding fragment thereof of claim 318, wherein the enzymatic activity is in the extracellular domain of the PSMA molecule.
321. The isolated antibody or antigen-binding fragment thereof of claim 318, wherein the antibody or antigen-binding fragment thereof specifically binds to an extracellular domain of PSMA.
322. A composition comprising an isolated antibody or antigen-binding fragment thereof as in any of claims 310 - 321, and an immunostimulatory oligonucleotide.
323. A composition comprising an isolated antibody or antigen-binding fragment thereof as in any of claims 310 - 321, and a cytokine.
324. The composition of claim 323, wherein the cytokine is selected from the group consisting of IL-2, IL-12, IL-18 and GM-CSF.
325. The composition of any of claims 322 - 324, further comprising a pharmaceutically- acceptable carrier.
326. A method for inducing an immune response comprising administering to a subject in need of such treatment an effective amount of the isolated antibody or composition of any of claims 310-325.
327. An isolated antibody or antigen-binding fragment thereof that selectively binds a PSMA protein multimer and inhibits at least one enzymatic activity of PSMA. 180
328. The isolated antibody or antigen-binding fragment thereof of claim 327, wherein the enzyme is selected from the group consisting of hydrolases and peptidases.
329. The isolated antibody or antigen-binding fragment thereof of claim 328, wherein the hydrolase is selected from the group consisting of folate hydrolase and γ-glutamyl hydrolase.
330. The isolated antibody or antigen-binding fragment thereof of claim 329, wherein the hydrolase is folate hydrolase and the antibody is mAb 5.4 or mAb 3.9.
331. The isolated antibody or antigen-binding fragment thereof of claim 328, wherein the peptidase is selected from the group consisting of NAALADase and dipeptidyl dipeptidase IV.
332. The isolated antibody or antigen-binding fragment thereof of claim 327, wherein the enzyme is active in cancer cells and has lesser activity in normal cells than in cancer cells or no activity in normal cells.
333. The isolated antibody or antigen-binding fragment thereof of claim 332, wherein the cancer cells are prostate cancer cells.
334. An isolated antibody or antigen-binding fragment thereof that selectively binds a PSMA protein multimer and enhances at least one enzymatic activity of PSMA.
335. The isolated antibody or antigen-binding fragment thereof of claim 334, wherein the enzyme is selected from the group consisting of hydrolases and peptidases.
336. The isolated antibody or antigen-binding fragment thereof of claim 335, wherein the hydrolase is selected from the group consisting of folate hydrolase and γ-glutamyl hydrolase.
337. The isolated antibody or antigen-binding fragment thereof of claim 335, wherein the peptidase is selected from the group consisting of NAALADase and dipeptidyl dipeptidase IV. 181
338. The isolated antibody or antigen-binding fragment thereof of claim 334, wherein the enzyme is active in normal cells and has lesser activity in cancer cells than in normal cells or no activity in cancer cells.
339. The isolated antibody or antigen-binding fragment thereof of claim 338, wherein the cancer cells are prostate cancer cells.
340. An isolated antibody or antigen-binding fragment thereof that selectively binds a PSMA protein multimer, wherein the isolated antibody is raised by immunizing an animal with a preparation comprising a PSMA protein multimer.
341. A composition comprising the isolated antibody or antigen-binding fragment thereof of claims 327 - 340, and a pharmaceutically acceptable carrier.
342. A composition comprising an isolated PSMA protein multimer.
343. The composition of claim 342, wherein the PSMA protein multimer is a dimer.
344. The composition of claim 342, wherein the composition comprises at least about 10% PSMA protein multimer.
345. The composition of claim 344, wherein the composition comprises at least about 20% PSMA protein multimer.
346. The composition of claim 345, wherein the composition comprises at least about 30% PSMA protein multimer.
347. The composition of claim 346, wherein the composition comprises at least about 40% PSMA protein multimer.
348. The composition of claim 347, wherein the composition comprises at least about 50% PSMA protein multimer. 182
349 The composition of claim 348, wherein the composition comprises at least about 75% PSMA protein multimer.
350. The composition of claim 349, wherein the composition comprises at least about 90% PSMA protein multimer.
351. The composition of claim 350, wherein the composition comprises at least about 95% PSMA protein multimer.
352. The composition of claim 342, wherein the PSMA protein multimer comprises noncovalently associated PSMA proteins.
353. The composition of claim 352, wherein the PSMA proteins are noncovalently associated under nondenaturing conditions.
354. The composition of any of claims 342-353, wherein at least one of the PSMA proteins forming the multimer is a recombinant, soluble PSMA (rsPSMA) polypeptide.
355. The composition of claim 342, wherein the PSMA protein multimer is reactive with a conformation-specific antibody that specifically recognizes PSMA.
356. The composition of claim 342, wherein the PSMA protein multimer comprises PSMA proteins in a native conformation.
357. The composition of claim 342, wherein the PSMA multimer is enzymatically active.
358. The composition of claim 357, wherein the enzymatic activity is selected from the group consisting of folate hydrolase activity, NAALADase activity, dipeptidyl dipeptidase IV activity, γ-glutamyl hydrolase activity and combinations thereof.
359. The composition of any of claims 342-358, further comprising an adjuvant.
360. The composition of any of claims 342-358, further comprising a cytokine.
AMENDED SHEET (ARTICLE 1§) } 183
361. The composition of claim 360, wherein the cytokine is selected from the group consisting of IL-2, IL-12, IL-18 and GM-CSF.
362. The composition of any of claims 342-361, further comprising a pharmaceutically acceptable carrier.
363. A method for inducing an immune response comprising administering to a subject in need of such treatment an effective amount of the composition of any of claims 342-362.
364. An isolated recombinant soluble PSMA (rsPSMA) protein multimer.
365. An isolated rsPSMA protein dimer.
366. The isolated rsPSMA protein dimer of claim 365, wherein the dimer comprises noncovalently associated rsPSMA proteins.
367. The isolated rsPSMA protein dimer of claim 366, wherein the rsPSMA proteins are noncovalently associated under nondenaturing conditions.
368. The isolated rsPSMA protein dimer of claim 365, wherein the isolated rsPSMA dimer is reactive with a conformation-specific antibody that specifically recognizes PSMA.
369. The isolated rsPSMA protein dimer of claim 365, wherein the isolated rsPSMA dimer is enzymatically active.
370. The isolated rsPSMA protein dimer of claim 369, wherein the enzymatic activity is selected from the group consisting of folate hydrolase activity, NAALADase activity, dipeptidyl dipeptidase IV activity, γ-glutamyl hydrolase activity and combinations thereof.
371. A method of screening for a candidate agent that inhibits at least one enzymatic activity of a PSMA enzyme comprising 184
a) mixing the candidate agent with an isolated PSMA protein multimer to form a reaction mixture, followed by b) adding a substrate for the PSMA enzyme to the reaction mixture, and c) determining the amount of a product formed from the substrate by the PSMA enzyme, wherein a decrease in the amount of product formed in comparison to a control is indicative of an agent capable of inhibiting at least one enzymatic activity of the PSMA enzyme.
372. The method of screening of claim 371, wherein the PSMA enzyme is selected from the group consisting of NAALADase, folate hydrolase, dipeptidyl dipeptidase IV and γ-glutamyl hydrolase.
373. The method of screening of claim 371, wherein the PSMA multimer comprises recombinant soluble PSMA.
374. The method of screening of claim 371, wherein the candidate agent is selected from the group consisting of an antibody, a small organic compound, or a peptide.
375. A candidate agent that inhibits at least one enzymatic activity of PSMA identified according to the method of claim 371.
376. The candidate agent according to claim 375, wherein the agent is selected from a combinatorial antibody library, a combinatorial protein library, or a small organic molecule library.
377. A method of screening for a candidate agent that enhances at least one enzymatic activity of a PSMA enzyme comprising a) mixing the candidate agent with an isolated PSMA protein multimer to form a reaction mixture, followed by b) adding a substrate for the PSMA enzyme to the reaction mixture, and c) determining the amount of a product formed from the substrate by the PSMA enzyme, wherein an increase in the amount of product formed in comparison to a control is 185
indicative of an agent capable of enhancing at least one enzymatic activity of the PSMA enzyme.
378. The method of screening of claim 377, wherein the PSMA enzyme is selected from the group consisting of NAALADase, folate hydrolase, dipeptidyl dipeptidase IV and γ-glutamyl hydrolase.
379. The method of screening of claim 377, wherein the PSMA multimer comprises recombinant soluble PSMA.
380. The method of screening of claim 377, wherein the candidate agent is selected from the group consisting of an antibody, a small organic compound, or a peptide.
381. A candidate agent that enhances at least one enzymatic activity of PSMA identified according to the method of claim 377.
382. The candidate agent according to claim 381, wherein the agent is selected from a combinatorial antibody library, a combinatorial protein library, or a small organic molecule library.
383. A method for identifying a compound that promotes dissociation of PSMA dimers, comprising contacting a PSMA dimer with a compound under conditions that do not promote dissociation of the PSMA dimer in the absence of the compound; measuring the amount of PSMA monomer; and comparing the amount of PSMA monomer measured in the presence of the compound with that observed in the absence of the compound; wherein an increase in the amount of PSMA monomer measured in the presence of the compound indicates that the compound is capable of promoting dissociation of the PSMA dimer.
384. A method for identifying a compound that promotes dissociation of PSMA dimers, comprising 186
contacting a PSMA dimer with a compound under conditions that do not promote dissociation of the PSMA dimer in the absence of the compound; measuring the amount of PSMA dimer; and comparing the amount of PSMA dimer measured in the presence of the compound with that observed in the absence of the compound; wherein a decrease in the amount of PSMA dimer measured in the presence of the compound indicates that the compound is capable of promoting dissociation of the PSMA dimer.
385. A method for identifying a compound that promotes dissociation of PSMA dimers, comprising contacting a PSMA dimer with a compound under conditions that do not promote dissociation of the PSMA dimer in the absence of the compound; measuring the amounts of PSMA monomer and PSMA dimer; calculating a ratio of PSMA monomer to PSMA dimer; and comparing the ratio obtained in the presence of the compound with that obtained in the absence of the compound; wherein an increase in the ratio measured in the presence of the compound indicates that the compound is capable of promoting dissociation of the PSMA dimer.
PCT/US2002/033944 2001-10-23 2002-10-23 Psma antibodies and protein multimers WO2003034903A2 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
AU2002356844A AU2002356844C1 (en) 2001-10-23 2002-10-23 PSMA antibodies and protein multimers
JP2003537481A JP5355839B2 (en) 2001-10-23 2002-10-23 PSMA antibodies and protein multimers
CA2464239A CA2464239C (en) 2001-10-23 2002-10-23 Psma antibodies and protein multimers
EP02802198A EP1448588A4 (en) 2001-10-23 2002-10-23 Psma antibodies and protein multimers
US10/395,894 US7850971B2 (en) 2001-10-23 2003-03-21 PSMA antibodies and protein multimers
US10/695,667 US20040161776A1 (en) 2001-10-23 2003-10-27 PSMA formulations and uses thereof
US10/976,352 US20050215472A1 (en) 2001-10-23 2004-10-27 PSMA formulations and uses thereof
US11/983,372 US8114965B2 (en) 2001-10-23 2007-11-07 Compositions of PSMA antibodies
US12/845,686 US8470330B2 (en) 2001-10-23 2010-07-28 PSMA antibodies and uses thereof
US13/608,337 US9695248B2 (en) 2001-10-23 2012-09-10 PSMA antibodies and uses thereof

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US33521501P 2001-10-23 2001-10-23
US60/335,215 2001-10-23
US36274702P 2002-03-07 2002-03-07
US60/362,747 2002-03-07
US41261802P 2002-09-20 2002-09-20
US60/412,618 2002-09-20

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10/395,894 Continuation-In-Part US7850971B2 (en) 2001-10-23 2003-03-21 PSMA antibodies and protein multimers
US10/695,667 Continuation-In-Part US20040161776A1 (en) 2001-10-23 2003-10-27 PSMA formulations and uses thereof

Publications (3)

Publication Number Publication Date
WO2003034903A2 WO2003034903A2 (en) 2003-05-01
WO2003034903A3 WO2003034903A3 (en) 2003-10-30
WO2003034903B1 true WO2003034903B1 (en) 2004-05-13

Family

ID=27407041

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/033944 WO2003034903A2 (en) 2001-10-23 2002-10-23 Psma antibodies and protein multimers

Country Status (7)

Country Link
US (2) US7850971B2 (en)
EP (4) EP1448588A4 (en)
JP (3) JP5355839B2 (en)
AU (1) AU2002356844C1 (en)
CA (1) CA2464239C (en)
ES (2) ES2606537T3 (en)
WO (1) WO2003034903A2 (en)

Families Citing this family (110)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7105159B1 (en) 1992-11-05 2006-09-12 Sloan-Kettering Institute For Cancer Research Antibodies to prostate-specific membrane antigen
US6569432B1 (en) * 1995-02-24 2003-05-27 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen and uses thereof
US7381407B1 (en) 1996-03-25 2008-06-03 Medarex, Inc. Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen
US6962981B1 (en) 1996-03-25 2005-11-08 Medarex, Inc. Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen
US7514078B2 (en) * 2001-06-01 2009-04-07 Cornell Research Foundation, Inc. Methods of treating prostate cancer with anti-prostate specific membrane antigen antibodies
US20040161776A1 (en) * 2001-10-23 2004-08-19 Maddon Paul J. PSMA formulations and uses thereof
WO2003034903A2 (en) 2001-10-23 2003-05-01 Psma Development Company, L.L.C. Psma antibodies and protein multimers
US20050215472A1 (en) 2001-10-23 2005-09-29 Psma Development Company, Llc PSMA formulations and uses thereof
MXPA04007262A (en) * 2002-01-28 2004-10-29 Medarex Inc Human monoclonal antibodies to prostate specific membrane antigen (psma).
PT1545613E (en) 2002-07-31 2011-09-27 Seattle Genetics Inc Auristatin conjugates and their use for treating cancer, an autoimmune disease or an infectious disease
CA2514419A1 (en) * 2003-01-28 2004-08-12 Proscan Rx Pharma Inc. Prostate cancer diagnosis and treatment
AU2003903501A0 (en) * 2003-07-07 2003-07-24 Commonwealth Scientific And Industrial Research Organisation A method of forming a reflective authentication device
BR122018071808B8 (en) 2003-11-06 2020-06-30 Seattle Genetics Inc conjugate
US7348413B2 (en) * 2004-02-26 2008-03-25 Arius Research Inc. Cancerous disease modifying antibodies
JP4560314B2 (en) * 2004-03-17 2010-10-13 ジェイファーマ株式会社 Method for detecting cancer with neutral amino acid transporter and kit for the same
CA2606138A1 (en) * 2004-04-19 2005-10-27 Proscan Rx Pharma Prostate cancer diagnosis and treatment
EP1817336B1 (en) 2004-11-12 2019-01-09 Seattle Genetics, Inc. Auristatins having an aminobenzoic acid unit at the n terminus
PL1833506T3 (en) * 2004-12-29 2016-01-29 Mannkind Corp Use of compositions comprising various tumor-associated antigens as anti-cancer vaccines
WO2006089231A2 (en) 2005-02-18 2006-08-24 Medarex, Inc. Monoclonal antibodies against prostate specific membrane antigen (psma) lacking in fucosyl residues
US20090297438A1 (en) * 2005-02-18 2009-12-03 Haichun Huang Human Monoclonal Antibodies to Prostate Specific Membrane Antigen (PSMA)
DK1874821T3 (en) 2005-04-26 2013-07-08 Trion Pharma Gmbh Combination of antibodies with glycocorticoids to treat cancer
EP1726650A1 (en) * 2005-05-27 2006-11-29 Universitätsklinikum Freiburg Monoclonal antibodies and single chain antibody fragments against cell-surface prostate specific membrane antigen
CA2612762C (en) * 2005-06-20 2013-12-10 Psma Development Company, Llc Psma antibody-drug conjugates
US8871720B2 (en) 2005-07-07 2014-10-28 Seattle Genetics, Inc. Monomethylvaline compounds having phenylalanine carboxy modifications at the C-terminus
EP3498289A1 (en) 2005-07-07 2019-06-19 Seattle Genetics, Inc. Monomethylvaline compounds having phenylalanine side-chain modifications at the c-terminus
EP1979410B1 (en) * 2005-12-29 2012-08-22 Life Technologies Corporation Compositions and methods for improving resolution of biomolecules separated on polyacrylamide gels
US7750116B1 (en) 2006-02-18 2010-07-06 Seattle Genetics, Inc. Antibody drug conjugate metabolites
SG183044A1 (en) 2007-07-16 2012-08-30 Genentech Inc Humanized anti-cd79b antibodies and immunoconjugatesand methods of use
ES2381788T3 (en) 2007-07-16 2012-05-31 Genentech, Inc. Anti-CD79b and immunoconjugate antibodies and methods of use
EP3714906A1 (en) * 2007-10-03 2020-09-30 Cornell University Treatment of proliferative disorders using radiolabelled antibodies to psma
UA106586C2 (en) 2008-01-31 2014-09-25 Дженентек, Інк. Anti-cd79b antibodies and imunokonugate and methods for their use
CA2718942A1 (en) 2008-03-18 2009-09-24 Seattle Genetics, Inc. Auristatin drug linker conjugates
US20110189093A1 (en) * 2008-04-14 2011-08-04 Proscan Rx Pharma Prostate specific membrane antigen antibodies and antigen binding fragments
EP2727606A3 (en) 2008-09-08 2015-09-23 Psma Development Company, L.L.C. Compounds for killing psma-expressing, taxane-resistant cancer cells
EP2352763B2 (en) * 2008-10-01 2022-09-21 Amgen Research (Munich) GmbH Bispecific single chain antibodies with specificity for high molecular weight target antigens
WO2010096486A1 (en) * 2009-02-17 2010-08-26 Cornell Research Foundation, Inc. Methods and kits for diagnosis of cancer and prediction of therapeutic value
US20140161800A1 (en) 2011-04-22 2014-06-12 John W. Blankenship Prostate-Specific Membrane Antigen Binding Proteins and Related Compositions and Methods
CN104619349B (en) 2012-06-07 2018-07-10 Ambrx公司 Prostate-specific membrane antigen antibody drug conjugate
JP2015521602A (en) 2012-06-14 2015-07-30 アンブルックス, インコーポレイテッドAmbrx, Inc. Anti-PSMA antibodies conjugated to nuclear receptor ligand polypeptides
WO2013192242A2 (en) * 2012-06-18 2013-12-27 University Of Southern California Cell surface marker and methods of use thereof
HUE045435T2 (en) 2012-10-12 2019-12-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
UY35148A (en) 2012-11-21 2014-05-30 Amgen Inc HETERODIMERIC IMMUNOGLOBULINS
WO2014140174A1 (en) 2013-03-13 2014-09-18 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
WO2014144817A2 (en) 2013-03-15 2014-09-18 Amgen Inc. Inhibitory polypeptides specific to wnt inhibitors
WO2015035215A1 (en) 2013-09-05 2015-03-12 Amgen Inc. Fc-containing molecules exhibiting predictable, consistent, and reproducible glycoform profiles
US20150110814A1 (en) 2013-10-18 2015-04-23 Psma Development Company, Llc Combination therapies with psma ligand conjugates
JP6908964B2 (en) 2013-10-18 2021-07-28 ピーエスエムエー ディベロップメント カンパニー，エルエルシー Combination therapy with PSMA ligand conjugate
WO2015073896A2 (en) 2013-11-15 2015-05-21 Psma Development Company, Llc Biomarkers for psma targeted therapy for prostate cancer
KR20220044377A (en) 2014-04-03 2022-04-07 아이쥐엠 바이오사이언스 인코포레이티드 Modified j-chain
CA2949237C (en) 2014-05-16 2022-08-23 Amgen Inc. Assay for detecting th1 and th2 cell populations
JP6531166B2 (en) 2014-09-10 2019-06-12 メドイミューン・リミテッドＭｅｄＩｍｍｕｎｅ Ｌｉｍｉｔｅｄ Pyrrolobenzodiazepine and its conjugate
EP3689910A3 (en) 2014-09-23 2020-12-02 F. Hoffmann-La Roche AG Method of using anti-cd79b immunoconjugates
CN107849148B (en) 2015-05-21 2023-09-19 哈普恩治疗公司 Trispecific binding proteins and methods of use
MX2017017172A (en) 2015-06-22 2018-02-23 Bayer Pharma AG Antibody drug conjugates (adcs) and antibody prodrug conjugates (apdcs) with enzymatically cleavable groups.
JOP20160154B1 (en) * 2015-07-31 2021-08-17 Regeneron Pharma Anti-psma antibodies, bispecific antigen-binding molecules that bind psma and cd3, and uses thereof
WO2017053469A2 (en) 2015-09-21 2017-03-30 Aptevo Research And Development Llc Cd3 binding polypeptides
ES2819870T3 (en) 2015-09-30 2021-04-19 Igm Biosciences Inc Modified J-chain binding molecules
CN108463245A (en) 2015-09-30 2018-08-28 Igm生物科学有限公司 The binding molecule of J chains with modification
WO2017060322A2 (en) 2015-10-10 2017-04-13 Bayer Pharma Aktiengesellschaft Ptefb-inhibitor-adc
EP3402824A1 (en) 2016-01-12 2018-11-21 Crescendo Biologics Limited Therapeutic molecules
KR20180123047A (en) 2016-03-24 2018-11-14 바이엘 파마 악티엔게젤샤프트 Prodrugs of cytotoxic activators with enzymatically cleavable groups
US11414497B2 (en) 2016-04-13 2022-08-16 Orimabs Ltd. Anti-PSMA antibodies and use thereof
GB201607968D0 (en) 2016-05-06 2016-06-22 Crescendo Biolog Ltd Chimeric antigen receptor
WO2017201488A1 (en) 2016-05-20 2017-11-23 Harpoon Therapeutics, Inc. Single domain serum albumin binding protein
US11623958B2 (en) 2016-05-20 2023-04-11 Harpoon Therapeutics, Inc. Single chain variable fragment CD3 binding proteins
CN116987189A (en) 2016-05-20 2023-11-03 哈普恩治疗公司 Single chain variable fragment CD3 binding proteins
CN117534764A (en) * 2016-06-06 2024-02-09 阿布泽纳(英国)有限公司 Antibodies, uses thereof and conjugates thereof
US11001636B2 (en) 2016-06-15 2021-05-11 Bayer Pharma Aktiengesellschaft Specific antibody-drug-conjugates (ADCs) with KSP inhibitors and anti-CD123-antibodies
GB201614162D0 (en) 2016-08-18 2016-10-05 Polytherics Ltd Antibodies, uses thereof and conjugates thereof
US20200023072A1 (en) 2016-10-11 2020-01-23 Medimmune Limited Antibody-drug conjugates with immune-mediated therapy agents
JP7215997B2 (en) 2016-11-23 2023-01-31 ハープーン セラピューティクス，インク． Trispecific proteins targeting prostate specific membrane antigen (PSMA) and methods of use
WO2018098354A1 (en) 2016-11-23 2018-05-31 Harpoon Therapeutics, Inc. Prostate specific membrane antigen binding protein
WO2018114798A1 (en) 2016-12-21 2018-06-28 Bayer Aktiengesellschaft Prodrugs of cytotoxic active agents having enzymatically cleavable groups
EP3558388A1 (en) 2016-12-21 2019-10-30 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) having enzymatically cleavable groups
EP3558387B1 (en) 2016-12-21 2021-10-20 Bayer Pharma Aktiengesellschaft Specific antibody drug conjugates (adcs) having ksp inhibitors
EP3565841A1 (en) 2017-01-06 2019-11-13 Crescendo Biologics Limited Single domain antibodies to programmed cell death (pd-1)
US11517627B2 (en) 2017-01-20 2022-12-06 Juno Therapeutics Gmbh Cell surface conjugates and related cell compositions and methods
CA3054248A1 (en) 2017-02-24 2018-08-30 Bayer As Combination therapy comprising a radiopharmaceutical and a dna-repair inhibitor
WO2018160754A2 (en) 2017-02-28 2018-09-07 Harpoon Therapeutics, Inc. Inducible monovalent antigen binding protein
SG10202109376YA (en) 2017-02-28 2021-10-28 Immunogen Inc Maytansinoid derivatives with self-immolative peptide linkers and conjugates thereof
CA3056011A1 (en) 2017-03-14 2018-09-20 Amgen Inc. Control of total afucosylated glycoforms of antibodies produced in cell culture
JP7284707B2 (en) 2017-04-07 2023-05-31 ジュノー セラピューティクス インコーポレイテッド Engineered Cells Expressing Prostate-Specific Membrane Antigen (PSMA) or Modified Forms Thereof and Related Methods
KR102376863B1 (en) 2017-05-12 2022-03-21 하푼 테라퓨틱스, 인크. mesothelin binding protein
EP3621648A4 (en) 2017-05-12 2021-01-20 Harpoon Therapeutics, Inc. Msln targeting trispecific proteins and methods of use
GB201711068D0 (en) 2017-07-10 2017-08-23 Crescendo Biologics Ltd Therapeutic molecules binding PSMA
CN111630070A (en) 2017-10-13 2020-09-04 哈普恩治疗公司 Trispecific proteins and methods of use
EA202090739A1 (en) 2017-10-13 2020-09-07 Харпун Терапьютикс, Инк. PROTEINS BINDING ANTIGEN OF MATURING B-CELLS
GB201802573D0 (en) 2018-02-16 2018-04-04 Crescendo Biologics Ltd Therapeutic molecules that bind to LAG3
EP3762410A4 (en) 2018-03-06 2022-04-06 The Trustees of the University of Pennsylvania Prostate-specific membrane antigen cars and methods of use thereof
MA52186A (en) 2018-03-26 2021-02-17 Amgen Inc TOTAL AFUCOSYLATED GLYCOFORMS OF ANTIBODIES PRODUCED IN CELL CULTURE
WO2019224275A1 (en) 2018-05-23 2019-11-28 Adc Therapeutics Sa Molecular adjuvant
US20220185910A1 (en) * 2018-06-18 2022-06-16 Eureka Therapeutics, Inc. Constructs targeting prostate-specific membrane antigen (psma) and uses thereof
US20210187134A1 (en) 2018-08-28 2021-06-24 Bayer As Combination of pi3k-inhibitors and targeted thorium conjugates
SG11202103022WA (en) 2018-09-25 2021-04-29 Harpoon Therapeutics Inc Dll3 binding proteins and methods of use
EP3927374A1 (en) 2019-02-21 2021-12-29 Bayer Aktiengesellschaft Combination of pd-1/pd-l1 inhibitors and targeted thorium conjugates
EP3927339A1 (en) 2019-02-22 2021-12-29 Bayer Aktiengesellschaft Combination of ar antagonists and targeted thorium conjugates
WO2021062372A1 (en) 2019-09-26 2021-04-01 Amgen Inc. Methods of producing antibody compositions
US11180563B2 (en) 2020-02-21 2021-11-23 Harpoon Therapeutics, Inc. FLT3 binding proteins and methods of use
EP4130006A4 (en) 2020-03-25 2024-01-17 Jiangsu Hengrui Pharmaceuticals Co Ltd Anti-psma antibody-exatecan analogue conjugate and medical use thereof
IL297423A (en) * 2020-04-24 2022-12-01 Radiomedix Inc Composition, kit and method for diagnosis and treatment of prostate cancer
WO2021247892A1 (en) 2020-06-04 2021-12-09 Amgen Inc. Assessment of cleaning procedures of a biotherapeutic manufacturing process
JP2023548767A (en) 2020-10-15 2023-11-21 アムジエン・インコーポレーテツド Relative unpaired glycans in antibody production methods
US20230372528A1 (en) 2020-10-16 2023-11-23 University Of Georgia Research Foundation, Inc. Glycoconjugates
JP2023552812A (en) 2020-12-09 2023-12-19 ジャナックス セラピューティクス，インク． Compositions and methods related to tumor-activating antibodies targeting PSMA and effector cell antigens
GB202102396D0 (en) 2021-02-19 2021-04-07 Adc Therapeutics Sa Molecular adjuvant
AR126089A1 (en) 2021-06-07 2023-09-13 Amgen Inc USE OF FUCOSIDASE TO CONTROL THE LEVEL OF AFFUCOSYLATION OF GLUCOSYLATED PROTEINS
WO2023059607A1 (en) 2021-10-05 2023-04-13 Amgen Inc. Fc-gamma receptor ii binding and glycan content
WO2023215725A1 (en) 2022-05-02 2023-11-09 Fred Hutchinson Cancer Center Compositions and methods for cellular immunotherapy
WO2023222557A1 (en) * 2022-05-17 2023-11-23 Bayer Aktiengesellschaft Radiopharmaceutical complexes targeting prostate-specific membrane antigen and its combinations
EP4279092A1 (en) * 2022-05-17 2023-11-22 Bayer AG Radiopharmaceutical complexes targeting prostate-specific membrane antigen

Family Cites Families (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4554101A (en) 1981-01-09 1985-11-19 New York Blood Center, Inc. Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity
DE3432714A1 (en) 1984-09-06 1986-04-24 Behringwerke Ag, 3550 Marburg TUMOR THERAPEUTICS AND METHOD FOR THE PRODUCTION THEREOF
US5153118A (en) 1985-12-17 1992-10-06 Eastern Virginia Medical Authority Monoclonal antibodies having binding specificity to human prostate tumor-associated antigens and methods for employing the same
US5055559A (en) 1986-02-20 1991-10-08 Oncogen Anti-melanoma antibody MG-21 for diagnosis and therapy of human tumors
US5091178A (en) 1986-02-21 1992-02-25 Oncogen Tumor therapy with biologically active anti-tumor antibodies
JPH0695949B2 (en) 1987-09-08 1994-11-30 工業技術院長 Human IgG1 type monoclonal antibody
US5688657A (en) 1988-03-31 1997-11-18 International Bio-Immune Systems, Inc. Monoclonal antibodies against human colon carcinoma-associated antigens and uses therefor
US5162504A (en) 1988-06-03 1992-11-10 Cytogen Corporation Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients
FR2635008B1 (en) 1988-08-05 1990-11-16 Sanofi Sa ACTIVATOR FOR THE SPECIFIC PRODUCTIVITY OF RECOMBINANT ANIMAL CELLS BASED ON POLYVINYLPYRROLIDONE AND DEFINED CULTURE MEDIUM CONTAINING THE SAME
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US5175384A (en) 1988-12-05 1992-12-29 Genpharm International Transgenic mice depleted in mature t-cells and methods for making transgenic mice
IL94872A (en) 1989-06-30 1995-03-30 Oncogen Monoclonal or chimeric antibodies reactive with human carcinomas, recombinant proteins comprising their antigen binding region, pharmaceutical compositions and kits comprising said antibodies and methods for imaging human carcinoma using same
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5124471A (en) 1990-03-26 1992-06-23 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Bifunctional dtpa-type ligand
US5281699A (en) 1990-06-01 1994-01-25 Tanox Biosystems, Inc. Treating B cell lymphoma or leukemia by targeting specific epitopes on B cell bound immunoglobulins
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
AU669124B2 (en) 1991-09-18 1996-05-30 Kyowa Hakko Kirin Co., Ltd. Process for producing humanized chimera antibody
ES2171410T3 (en) 1991-11-26 2002-09-16 Jenner Technologies ANTITUMOR VACCINES.
CA2452130A1 (en) 1992-03-05 1993-09-16 Francis J. Burrows Methods and compositions for targeting the vasculature of solid tumors
US5756825A (en) 1992-09-08 1998-05-26 Safavy; Ahmad Hydroxamic acid-based bifunctional chelating compounds
US5489525A (en) 1992-10-08 1996-02-06 The United States Of America As Represented By The Department Of Health And Human Services Monoclonal antibodies to prostate cells
US7070782B1 (en) 1992-11-05 2006-07-04 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen
EP1757694A3 (en) 1992-11-05 2008-02-27 Sloan Kettering Institute For Cancer Research Prostate-specific membrane antigen
US6953668B1 (en) 1992-11-05 2005-10-11 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen
US7105159B1 (en) 1992-11-05 2006-09-12 Sloan-Kettering Institute For Cancer Research Antibodies to prostate-specific membrane antigen
US6034065A (en) 1992-12-03 2000-03-07 Arizona Board Of Regents Elucidation and synthesis of antineoplastic tetrapeptide phenethylamides of dolastatin 10
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
US5925362A (en) 1993-08-11 1999-07-20 Jenner Technologies Method to elicit an antitumor response with human prostate-specific antigen
US6015686A (en) 1993-09-15 2000-01-18 Chiron Viagene, Inc. Eukaryotic layered vector initiation systems
US6569432B1 (en) 1995-02-24 2003-05-27 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen and uses thereof
WO1996026272A1 (en) 1995-02-24 1996-08-29 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen and uses thereof
US5935818A (en) 1995-02-24 1999-08-10 Sloan-Kettering Institute For Cancer Research Isolated nucleic acid molecule encoding alternatively spliced prostate-specific membrane antigen and uses thereof
EP0690452A3 (en) 1994-06-28 1999-01-07 Advanced Micro Devices, Inc. Electrically erasable memory and method of erasure
US5541087A (en) 1994-09-14 1996-07-30 Fuji Immunopharmaceuticals Corporation Expression and export technology of proteins as immunofusins
US6011021A (en) 1996-06-17 2000-01-04 Guilford Pharmaceuticals Inc. Methods of cancer treatment using naaladase inhibitors
US5994292A (en) 1995-05-31 1999-11-30 The United States Of America As Represented By The Department Of Health And Human Services Interferon-inducible protein 10 is a potent inhibitor of angiogenesis
US5773292A (en) 1995-06-05 1998-06-30 Cornell University Antibodies binding portions, and probes recognizing an antigen of prostate epithelial cells but not antigens circulating in the blood
US5788963A (en) 1995-07-31 1998-08-04 Pacific Northwest Cancer Foundation Isolation and/or preservation of dendritic cells for prostate cancer immunotherapy
US6224870B1 (en) 1997-01-24 2001-05-01 Genitrix, Ltd. Vaccine compositions and methods of modulating immune responses
US20040253246A1 (en) 1996-02-23 2004-12-16 Israeli Ron S. Prostate-specific membrane antigen and uses thereof
US6962981B1 (en) 1996-03-25 2005-11-08 Medarex, Inc. Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen
US7381407B1 (en) 1996-03-25 2008-06-03 Medarex, Inc. Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen
US6150508A (en) 1996-03-25 2000-11-21 Northwest Biotherapeutics, Inc. Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen
DK0914155T3 (en) * 1996-03-25 2006-06-26 Medarex Inc Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen
US6451592B1 (en) 1996-04-05 2002-09-17 Chiron Corporation Recombinant alphavirus-based vectors with reduced inhibition of cellular macromolecular synthesis
US20010036928A1 (en) 1996-04-22 2001-11-01 Chamberlain Ronald S. Heterologous boosting immunizations
US6107090A (en) 1996-05-06 2000-08-22 Cornell Research Foundation, Inc. Treatment and diagnosis of prostate cancer with antibodies to extracellur PSMA domains
US6136311A (en) 1996-05-06 2000-10-24 Cornell Research Foundation, Inc. Treatment and diagnosis of cancer
US5795877A (en) 1996-12-31 1998-08-18 Guilford Pharmaceuticals Inc. Inhibitors of NAALADase enzyme activity
US5804602A (en) * 1996-06-17 1998-09-08 Guilford Pharmaceuticals Inc. Methods of cancer treatment using naaladase inhibitors
IL127605A0 (en) 1996-06-17 1999-10-28 Guilford Pharm Inc Methods of cancer treatment using naaladase inhibitors
US6017903A (en) 1996-09-27 2000-01-25 Guilford Pharmaceuticals Inc. Pharmaceutical compositions and methods of treating a glutamate abnormality and effecting a neuronal activity in an animal using NAALADase inhibitors
US5672592A (en) 1996-06-17 1997-09-30 Guilford Pharmaceuticals Inc. Certain phosphonomethyl-pentanedioic acid derivatives thereof
US6046180A (en) 1996-06-17 2000-04-04 Guilford Pharmaceuticals Inc. NAALADase inhibitors
US5922845A (en) 1996-07-11 1999-07-13 Medarex, Inc. Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies
EP2218775B1 (en) 1996-08-30 2015-01-28 Life Technologies Corporation Method for producing a polypeptide in vitro in mammalian cells in a protein-free and serum-free culture medium
PL332413A1 (en) 1996-09-27 1999-09-13 Guilford Pharm Inc Compositions containing inhibitors of naaladase as well as methods of treating glutamatic anomaly and influencing neuronic functions among animals
EP0959893A4 (en) 1996-12-10 2004-11-10 Sloan Kettering Institutefor C Stimulation of an immune response to a differentiation antigen stimulated by an altered antigen
US20020155093A1 (en) 1997-02-18 2002-10-24 Houghton Alan N. Method for stimulation of an immune response to a differentiation antigen stimulated by an altered antigen
WO1998036765A1 (en) 1997-02-25 1998-08-27 Arizona Board Of Regents Isolation and structural elucidation of the cytostatic linear and cyclo-depsipeptides dolastatin 16, dolastatin 17, and dolastatin 18
EP0994707A4 (en) 1997-05-27 2001-11-14 Guilford Pharm Inc Inhibitors of naaladase enzyme activity
US6977074B2 (en) 1997-07-10 2005-12-20 Mannkind Corporation Method of inducing a CTL response
US5981209A (en) 1997-12-04 1999-11-09 Guilford Pharmaceuticals Inc. Use of NAALADase activity to identify prostate cancer and benign prostatic hyperplasia
US6372955B1 (en) * 1998-02-17 2002-04-16 Ortho Mcneil Pharmaceutical, Inc. Methods for Producing B cells and antibodies from H2-O modified transgenic mice
FR2776702B1 (en) 1998-03-24 2000-05-05 Elf Exploration Prod METHOD FOR CONDUCTING A HYDROCARBON PRODUCTION FACILITY
US6200765B1 (en) 1998-05-04 2001-03-13 Pacific Northwest Cancer Foundation Non-invasive methods to detect prostate cancer
JP2000080100A (en) * 1998-06-17 2000-03-21 Japan Tobacco Inc Human monoclonal antibody against parathyroid hormone-related protein
ES2251204T3 (en) 1998-07-06 2006-04-16 Mgi Gp, Inc. NAALADASA INHIBITORS USEFUL AS PHARMACEUTICAL COMPOUNDS AND COMPOSITIONS.
US6395718B1 (en) 1998-07-06 2002-05-28 Guilford Pharmaceuticals Inc. Pharmaceutical compositions and methods of inhibiting angiogenesis using naaladase inhibitors
IL125608A0 (en) 1998-07-30 1999-03-12 Yeda Res & Dev Tumor associated antigen peptides and use of same as anti-tumor vaccines
EP1109921A4 (en) 1998-09-04 2002-08-28 Sloan Kettering Inst Cancer Fusion receptors specific for prostate-specific membrane antigen and uses thereof
US6387888B1 (en) 1998-09-30 2002-05-14 American Foundation For Biological Research, Inc. Immunotherapy of cancer through expression of truncated tumor or tumor-associated antigen
US6444657B1 (en) 1998-12-31 2002-09-03 Guilford Pharmaceuticals Inc. Methods for treating certain diseases using naaladase inhibitors
ATE465266T1 (en) 1998-12-31 2010-05-15 Novartis Vaccines & Diagnostic COMPOSITIONS AND METHODS FOR PACKAGING ALPAVIRUS VECTORS
US6329201B1 (en) 1998-12-31 2001-12-11 Chiron Corporation Compositions and methods for packaging of alphavirus vectors
DE60039032D1 (en) 1999-03-01 2008-07-10 Commw Scient Ind Res Org REGULATORY CONSTRUCTS, THE INTRON 3 OF THE PR
US6897062B1 (en) 1999-04-09 2005-05-24 Sloan-Kettering Institute For Cancer Research DNA encoding the prostate-specific membrane antigen-like gene and uses thereof
EP1177207A4 (en) 1999-04-09 2003-06-04 Sloan Kettering Inst Cancer Dna encoding the prostate-specific membrane antigen-like gene and uses thereof
EP1553414A1 (en) 1999-04-13 2005-07-13 Medarex, Inc. Methods for the diagnosis and treatment of metastatic prostate tumors
JP2002540814A (en) 1999-04-13 2002-12-03 ノースウエスト バイオセラピューティクス，インコーポレイティド Methods for diagnosis and treatment of metastatic prostate tumor
US6528499B1 (en) 2000-04-27 2003-03-04 Georgetown University Ligands for metabotropic glutamate receptors and inhibitors of NAALADase
EP1512755A3 (en) 1999-06-10 2007-11-21 Sloan-Kettering Institute For Cancer Research Markers for prostate cancer
JP2003535024A (en) 1999-06-29 2003-11-25 エピミューン インコーポレイテッド HLA binding peptides and uses thereof
MXPA02000961A (en) * 1999-07-29 2003-08-20 Medarex Inc Human monoclonal antibodies to prostate specific membrane antigen.
US6313159B1 (en) 1999-08-20 2001-11-06 Guilford Pharmaceuticals Inc. Metabotropic glutamate receptor ligand derivatives as naaladase inhibitors
FR2797743B1 (en) 1999-08-23 2003-08-08 Urogene PROSTATIC CELL LINE AND ITS USE FOR OBTAINING AN ESTABLISHED PROSTATIC TUMOR IN ANIMALS
WO2001019956A2 (en) 1999-09-13 2001-03-22 Bander Neil H A method for isolation of prostatic epithelial cells from semen
WO2001045728A2 (en) 1999-12-21 2001-06-28 Epimmune Inc. Inducing cellular immune responses to prostate cancer antigens using peptide and nucleic acid compositions
AU2001242190A1 (en) 2000-03-31 2001-10-15 Aventis Pasteur Limited Immunogenic peptides derived from prostate-specific membrane antigen (psma) and uses thereof
NZ534864A (en) 2000-05-08 2006-04-28 Celldex Therapeutics Inc Human monoclonal antibodies to dentritic cells
US7560534B2 (en) 2000-05-08 2009-07-14 Celldex Research Corporation Molecular conjugates comprising human monoclonal antibodies to dendritic cells
IL152655A0 (en) 2000-05-12 2003-06-24 Northwest Biotherapeutics Inc Method to increase class i presentation of exogenous antigens by human dendritic cells
WO2001091738A2 (en) 2000-05-30 2001-12-06 Guilford Pharmaceuticals Inc. Naaladase inhibitors for treating amyotrophic lateral sclerosis
DE60107022T2 (en) 2000-07-24 2005-11-24 Health Research Inc. Method for the detection of prostate-specific membrane antigen in serum
US6379550B1 (en) 2000-07-24 2002-04-30 Health Research, Inc. Method for detecting PSA and its molecular forms using thiophilic gel
CA2425648A1 (en) 2000-10-19 2002-04-19 Epimmune Inc. Hla class i and ii binding peptides and their uses
AU2002239441A1 (en) 2000-11-01 2002-05-27 American Foundation For Biological Research, Inc. Methods and compositions for inducing cell-mediated immune responses
EP1390523B1 (en) 2000-11-20 2007-05-09 Eastern Virginia Medical School Methods and devices for the quantitative detection of prostate specific membrane antigen and other prostatic markers
US20040018194A1 (en) 2000-11-28 2004-01-29 Francisco Joseph A. Recombinant anti-CD30 antibodies and uses thereof
JP2005505242A (en) 2001-03-07 2005-02-24 マンカインド コーポレイション Anti-neovascular preparation for cancer
WO2003008537A2 (en) 2001-04-06 2003-01-30 Mannkind Corporation Epitope sequences
EP1515982A4 (en) 2001-05-09 2005-10-26 Corixa Corp Compositions and methods for the therapy and diagnosis of prostate cancer
US20030007974A1 (en) 2001-05-30 2003-01-09 Nanus David M. Endopeptidase/anti-PSMA antibody fusion proteins for treatment of cancer
US7514078B2 (en) 2001-06-01 2009-04-07 Cornell Research Foundation, Inc. Methods of treating prostate cancer with anti-prostate specific membrane antigen antibodies
US7045605B2 (en) 2001-06-01 2006-05-16 Cornell Research Foundation, Inc. Modified antibodies to prostate-specific membrane antigen and uses thereof
US7666414B2 (en) 2001-06-01 2010-02-23 Cornell Research Foundation, Inc. Methods for treating prostate cancer using modified antibodies to prostate-specific membrane antigen
US7045335B2 (en) 2001-09-06 2006-05-16 Alphavax, Inc. Alphavirus replicon vector systems
US7192586B2 (en) 2001-09-20 2007-03-20 Cornell Research Foundation, Inc. Methods and compositions for treating or preventing skin disorders using binding agents specific for prostate specific membrane antigen
WO2003034903A2 (en) 2001-10-23 2003-05-01 Psma Development Company, L.L.C. Psma antibodies and protein multimers
US20050215472A1 (en) 2001-10-23 2005-09-29 Psma Development Company, Llc PSMA formulations and uses thereof
US20040161776A1 (en) 2001-10-23 2004-08-19 Maddon Paul J. PSMA formulations and uses thereof
US20040018519A1 (en) 2001-11-16 2004-01-29 Wright ,Jr. George L Methods and devices for quantitative detection of prostate specific membrane antigen and other prostatic markers
WO2003057921A1 (en) 2001-12-26 2003-07-17 Sloan Kettering Institute For Cancer Research Dna immunization with libraries of minigenes encoding degenerate variants of major histocompatibility class i restricted epitopes
EP1472541B1 (en) 2002-01-10 2009-09-16 The Johns Hopkins University Imaging agents and methods of imaging naaladase of psma
MXPA04007262A (en) 2002-01-28 2004-10-29 Medarex Inc Human monoclonal antibodies to prostate specific membrane antigen (psma).
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
WO2003073828A2 (en) 2002-03-01 2003-09-12 Applied Immune Technologies Immunotherapy for prostate cancer using recombinant bacille calmette-guerin expressing prostate specific antigens
PT1545613E (en) 2002-07-31 2011-09-27 Seattle Genetics Inc Auristatin conjugates and their use for treating cancer, an autoimmune disease or an infectious disease
WO2006028429A2 (en) 2002-08-05 2006-03-16 The Johns Hopkins University Peptides for targeting the prostate specific membrane antigen
US20040180354A1 (en) 2002-09-06 2004-09-16 Simard John J.L. Epitope sequences
TWI320716B (en) * 2002-10-14 2010-02-21 Abbott Lab Erythropoietin receptor binding antibodies
US20040136998A1 (en) 2002-10-30 2004-07-15 Bander Neil H. Methods and compositions for treating or preventing insulin-related disorders using binding agents specific for prostate specific membrane antigen
CA2514419A1 (en) 2003-01-28 2004-08-12 Proscan Rx Pharma Inc. Prostate cancer diagnosis and treatment
WO2004067564A2 (en) 2003-01-29 2004-08-12 Protein Design Labs, Inc. Compositions against cancer antigen liv-1 and uses thereof
AU2004273791A1 (en) 2003-09-05 2005-03-31 Genentech, Inc. Antibodies with altered effector functions
US20050202020A1 (en) 2004-01-09 2005-09-15 Jeffrey Ross Diagnosing and treating cancer
US7837980B2 (en) 2004-03-02 2010-11-23 Seattle Genetics, Inc. Partially loaded antibodies and methods of their conjugation
US8540968B2 (en) * 2004-03-02 2013-09-24 Cellectar, Inc. Phospholipid ether analogs as agents for detecting and locating cancer, and methods thereof
EP1610818A4 (en) 2004-03-03 2007-09-19 Millennium Pharm Inc Modified antibodies to prostate-specific membrane antigen and uses thereof
WO2005123129A2 (en) 2004-06-14 2005-12-29 Regents Of The University Of California Methods of redistributing apical target antigens to detect and treat cellular proliferative disease
WO2006013014A2 (en) 2004-08-04 2006-02-09 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with prostate-specific membrane antigen-like protein (psmal)
WO2006076525A2 (en) 2005-01-14 2006-07-20 Cytogen Corporation Combination cancer therapy with anti-psma antibodies
WO2006089231A2 (en) 2005-02-18 2006-08-24 Medarex, Inc. Monoclonal antibodies against prostate specific membrane antigen (psma) lacking in fucosyl residues
US20090297438A1 (en) 2005-02-18 2009-12-03 Haichun Huang Human Monoclonal Antibodies to Prostate Specific Membrane Antigen (PSMA)
WO2006093991A1 (en) 2005-03-02 2006-09-08 The Cleveland Clinic Foundation Compounds which bind psma and uses thereof
AU2006220621A1 (en) 2005-03-07 2006-09-14 Archemix Corp. Stabilized aptamers to PSMA and their use as prostate cancer therapeutics
AU2006235421A1 (en) 2005-04-08 2006-10-19 Cytogen Corporation Conjugated anti-PSMA antibodies
EP1726650A1 (en) 2005-05-27 2006-11-29 Universitätsklinikum Freiburg Monoclonal antibodies and single chain antibody fragments against cell-surface prostate specific membrane antigen
CA2612762C (en) 2005-06-20 2013-12-10 Psma Development Company, Llc Psma antibody-drug conjugates
US20100184699A1 (en) 2005-06-29 2010-07-22 Kyogo Itoh Peptide Derived From Prostate-Related Protein As Cancer Vaccine Candidate For Prostate Cancer Patient Who Is Positive For Hla-A3 Super-Type Allele Molecule
US7824659B2 (en) * 2005-08-10 2010-11-02 Lantheus Medical Imaging, Inc. Methods of making radiolabeled tracers and precursors thereof
US20080279868A1 (en) 2005-09-26 2008-11-13 Medarex, Inc. Antibody-Drug Conjugates and Methods of Use
EP1948688A2 (en) 2005-11-14 2008-07-30 Psma Development Company, L.L.C. Compositions of and methods of using stabilized psma dimers
WO2007103288A2 (en) 2006-03-02 2007-09-13 Seattle Genetics, Inc. Engineered antibody drug conjugates

Also Published As

Publication number Publication date
EP2363404B8 (en) 2016-12-07
CA2464239A1 (en) 2003-05-01
EP1448588A2 (en) 2004-08-25
EP2360169A3 (en) 2012-02-15
EP1448588A4 (en) 2006-10-25
WO2003034903A3 (en) 2003-10-30
WO2003034903A2 (en) 2003-05-01
EP2360169B1 (en) 2015-10-14
US20040033229A1 (en) 2004-02-19
EP3184539A2 (en) 2017-06-28
ES2606537T3 (en) 2017-03-24
AU2002356844C1 (en) 2010-03-04
JP2009102443A (en) 2009-05-14
JP2005523683A (en) 2005-08-11
JP5703447B2 (en) 2015-04-22
EP2363404A3 (en) 2012-01-25
US8114965B2 (en) 2012-02-14
EP2363404B1 (en) 2016-09-07
EP3184539A3 (en) 2017-09-13
US7850971B2 (en) 2010-12-14
US20080286284A1 (en) 2008-11-20
EP2360169A2 (en) 2011-08-24
JP2012245010A (en) 2012-12-13
EP2363404A2 (en) 2011-09-07
AU2002356844B2 (en) 2009-11-12
JP5355839B2 (en) 2013-11-27
CA2464239C (en) 2016-07-12
ES2559002T3 (en) 2016-02-10

Similar Documents

Publication Publication Date Title
WO2003034903B1 (en) Psma antibodies and protein multimers
JP2005523683A5 (en)
TWI787796B (en) Anti-cd71 antibodies, activatable anti-cd71 antibodies, and methods of use thereof
KR101220635B1 (en) Novel anti-ｉｇｆ-ｉｒ antibodies and uses thereof
US7332580B2 (en) Bispecific single chain Fv antibody molecules and methods of use thereof
US20180100020A1 (en) Chimeric rabbit/human ror1 antibodies
US7332585B2 (en) Bispecific single chain Fv antibody molecules and methods of use thereof
RU2656161C1 (en) Anti-her2 antibody and conjugate thereof
Friedländer et al. ErbB-directed immunotherapy: antibodies in current practice and promising new agents
US7399469B2 (en) Anti-LFL2 antibodies for the diagnosis, prognosis and treatment of cancer
US11680102B2 (en) Anti-BAFF receptor antibodies and uses thereof
US11643437B2 (en) Tandem repeat cancer-targeting peptides for molecular conjugation or engineering and uses thereof in cancer theranostics
US20030215453A1 (en) Methods of therapy and diagnosis using immunotargeting of cells expressing VpreB1 protein
CN112794911B (en) Humanized anti-folate receptor 1 antibody and application thereof
US10030076B2 (en) Antibodies against glioma biomarkers
JPWO2020176497A5 (en)
US20040048817A1 (en) Methods of immunotherapy and diagnosis
US20220411532A1 (en) Antibodies targeting an amphiregulin-derived cell surface neo-epitope
RU2193779C2 (en) Method and preparation for treating the cases of flat cell cancer
EP2009028A1 (en) Combination of a conventional anti-cancer treatment with anti-CD44 antibody administration for treating solid tumors

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 10395894

Country of ref document: US

AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2464239

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2003537481

Country of ref document: JP

Ref document number: 2002356844

Country of ref document: AU

B Later publication of amended claims

Effective date: 20030523

WWE Wipo information: entry into national phase

Ref document number: 2002802198

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2002802198

Country of ref document: EP