CA2198899A1 - Methods for producing antibody libraries using universal or randomized immunoglobulin light chains - Google Patents
Methods for producing antibody libraries using universal or randomized immunoglobulin light chainsInfo
- Publication number
- CA2198899A1 CA2198899A1 CA002198899A CA2198899A CA2198899A1 CA 2198899 A1 CA2198899 A1 CA 2198899A1 CA 002198899 A CA002198899 A CA 002198899A CA 2198899 A CA2198899 A CA 2198899A CA 2198899 A1 CA2198899 A1 CA 2198899A1
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- Prior art keywords
- oligonucleotide
- immunoglobulin
- light chain
- gene
- seq
- Prior art date
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- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract 23
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 title claims 10
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 title 1
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract 34
- 230000001939 inductive effect Effects 0.000 claims abstract 5
- 238000002703 mutagenesis Methods 0.000 claims abstract 5
- 231100000350 mutagenesis Toxicity 0.000 claims abstract 5
- 238000004519 manufacturing process Methods 0.000 claims abstract 4
- 239000002773 nucleotide Substances 0.000 claims 28
- 125000003729 nucleotide group Chemical group 0.000 claims 28
- 108090000623 proteins and genes Proteins 0.000 claims 19
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims 16
- 230000000295 complement effect Effects 0.000 claims 14
- 108700005091 Immunoglobulin Genes Proteins 0.000 claims 10
- 108060003951 Immunoglobulin Proteins 0.000 claims 9
- 102000018358 immunoglobulin Human genes 0.000 claims 9
- 238000003752 polymerase chain reaction Methods 0.000 claims 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 4
- 229920001184 polypeptide Polymers 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 108700029228 Immunoglobulin Heavy Chain Genes Proteins 0.000 claims 3
- 239000000427 antigen Substances 0.000 claims 3
- 108091007433 antigens Proteins 0.000 claims 3
- 102000036639 antigens Human genes 0.000 claims 3
- 241000894007 species Species 0.000 claims 3
- 108700029227 Immunoglobulin Light Chain Genes Proteins 0.000 claims 2
- 230000004186 co-expression Effects 0.000 claims 1
- 241000724791 Filamentous phage Species 0.000 abstract 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 1
- 239000002245 particle Substances 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/14—Peptides, e.g. proteins
- A61K49/16—Antibodies; Immunoglobulins; Fragments thereof
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1036—Retroviridae, e.g. leukemia viruses
- C07K16/1045—Lentiviridae, e.g. HIV, FIV, SIV
- C07K16/1063—Lentiviridae, e.g. HIV, FIV, SIV env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1037—Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/02—Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
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- Genetics & Genomics (AREA)
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- Engineering & Computer Science (AREA)
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- Veterinary Medicine (AREA)
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- Wood Science & Technology (AREA)
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- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
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- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Optics & Photonics (AREA)
- Radiology & Medical Imaging (AREA)
- Crystallography & Structural Chemistry (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Plant Pathology (AREA)
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- AIDS & HIV (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
Abstract
The present invention describes methods for producing antibody libraries, and particularly for increasing antibody library diversity by inducing mutagenesis within the CDR regions of immunoglobulun heavy or light chains that are displayed on the surface of filamentous phage particles comprising the library. The invention also describes oligonucleotides useful for increasing the library diiversity, and universal light chains useful in the library production methods.
Claims (37)
1. An oligonucleotide useful as a primer for inducing mutagenesis in a complementarity determining region (CDR) of an immunoglobulin light chain gene, said oligonucleotide having 3' and 5' termini and comprising:
a) a nucleotide sequence at said 3' terminus capable of hybridizing to a first framework region of an immunoglobulin gene;
b) a nucleotide sequence at said 5' terminus capable of hybridizing to a second framework region of an immunoglobulin gene; and c) a nucleotide sequence between said 3' and 5' termini according to the formula:
[NNK]n, wherein N is independently any nucleotide, K is G or T, n is 3 to about 24, said 3' and 5' terminal nucleotide sequences having a length of about 6 to 50 nucleotides, or an oligonucleotide having a sequence complementary thereto.
a) a nucleotide sequence at said 3' terminus capable of hybridizing to a first framework region of an immunoglobulin gene;
b) a nucleotide sequence at said 5' terminus capable of hybridizing to a second framework region of an immunoglobulin gene; and c) a nucleotide sequence between said 3' and 5' termini according to the formula:
[NNK]n, wherein N is independently any nucleotide, K is G or T, n is 3 to about 24, said 3' and 5' terminal nucleotide sequences having a length of about 6 to 50 nucleotides, or an oligonucleotide having a sequence complementary thereto.
2. The oligonucleotide of claim 1 wherein said 5' terminus has the nucleotide sequence 5' -TATACTGTCAGCAGTAT-3' (SEQ ID NO
26) or 5' -GATTTTGCAGTGTATTACTGTCAGQGTAT-3' (SEQ ID NO 27), or an oligonucleotide having a sequence complementary thereto.
26) or 5' -GATTTTGCAGTGTATTACTGTCAGQGTAT-3' (SEQ ID NO 27), or an oligonucleotide having a sequence complementary thereto.
3. The oligonucleotide of claim 1 wherein said 3' terminus has the nucleotide sequence 5' -ACTTTCGGCGGAGGGACQAGGTGGAG-3' (SEQ ID NO 28) or 5' -ACTTTCGGCGGAGGGACC-3' (SEQ ID NO 29), or an oligonucleotide having a sequence complementary thereto.
4. The oligonucleotide of claim 1 wherein n is 4, 5, 6, 10 or 16.
5. The oligonucleotide of claim 1 wherein said immunoglobulin is human.
6. The oligonucleotide of claim 1 wherein said CDR is CDR3.
7. The oligonucleotide of claim 1 according to the formula: 5' -GATTTTGCAGTGTATTACTGT [NNK] 10TTCGGCGGAGGGACCAAGGTGGAG-3' (SEQ ID NO 12), or an oligonucleotide having a sequence complementary thereto.
8. An oligonucleotide useful as a primer for inducing mutagenesis in a complementarity determining region (CDR) of an immunoglobulin light chain gene, said oligonucleotide having 3' and 5' termini and comprising:
a) a nucleotide sequence at said 3' terminus capable of hybridizing to a first framework region of an immunoglobulin gene;
b) a nucleotide sequence at said 5' terminus capable of hybridizing to a second framework region of an immunoglobulin gene; and c) a nucleotide sequence between said 3' and 5' termini according to the formula:
[MNN]n, wherein N is independently any nucleotide, M is A or C, n is 3 to about 24, said 3' and 5' terminal nucleotide sequences having a length of about 6 to 50 nucleotides, or an oligonucleotide having a sequence complementary thereto.
a) a nucleotide sequence at said 3' terminus capable of hybridizing to a first framework region of an immunoglobulin gene;
b) a nucleotide sequence at said 5' terminus capable of hybridizing to a second framework region of an immunoglobulin gene; and c) a nucleotide sequence between said 3' and 5' termini according to the formula:
[MNN]n, wherein N is independently any nucleotide, M is A or C, n is 3 to about 24, said 3' and 5' terminal nucleotide sequences having a length of about 6 to 50 nucleotides, or an oligonucleotide having a sequence complementary thereto.
9 . The oligonucleotide of claim 8 wherein said 5' terminus has the nucleotide sequence 5' -GTTCCACCTTGGTCCCTTGGCCGAA-3' (SEQ
ID NO 30), or an oligonucleotide having a sequence complementary thereto.
ID NO 30), or an oligonucleotide having a sequence complementary thereto.
10. The oligonucleotide of claim 8 wherein said 3' terminus has the nucleotide sequence 5' -ACAGTAGTACACTGCAAAATC-3' (SEQ ID
NO 31), or an oligonucleotide having a sequence complementary thereto.
NO 31), or an oligonucleotide having a sequence complementary thereto.
11. The oligonucleotide of claim 8 wherein n is 8, 10 or 16.
12. The oligonucleotide of claim 8 wherein said immunoglobulin is human.
13. The oligonucleotide of claim 8 wherein said CDR is CDR3.
14. A method for producing an antibody combining site in a polypeptide comprising inducing mutagenesis in a complementarity determining region (CDR) of an immunoglobulin light chain gene which comprises amplifying a CDR portion of the immunoglobulin gene by polymerase chain reaction (PCR) using a PCR primer oligonucleotide, said oligonucleotide having 3' and 5' termini and comprising:
a) a nucleotide sequence at said 3' terminus capable of hybridizing to a first framework region of an immunoglobulin gene;
b) a nucleotide sequence at said 5' terminus capable of hybridizing to a second framework region of an immunoglobulin gene; and c) a nucleotide sequence between said 3' and 5' termini according to the formula:
[NNK]n, wherein N is independently any nucleotide, K is G or T, and n is 3 to about 24, said 3' and 5' terminal nucleotide sequences having a length of about 6 to 50 nucleotides, or an oligonucleotide having a sequence complementary thereto.
a) a nucleotide sequence at said 3' terminus capable of hybridizing to a first framework region of an immunoglobulin gene;
b) a nucleotide sequence at said 5' terminus capable of hybridizing to a second framework region of an immunoglobulin gene; and c) a nucleotide sequence between said 3' and 5' termini according to the formula:
[NNK]n, wherein N is independently any nucleotide, K is G or T, and n is 3 to about 24, said 3' and 5' terminal nucleotide sequences having a length of about 6 to 50 nucleotides, or an oligonucleotide having a sequence complementary thereto.
15. The method of claim 14 wherein said 5' terminus has the nucleotide sequence 5'-TATACTGTCAGCAGTAT-3' (SEQ ID NO 26) or 5'-GATTTTGCAGTGTATTACTGTCAGCAGTAT-3' (SEQ ID NO 27), or an oligonucleotide having a sequence complementary thereto.
16 . The method of claim 14 wherein said 3' terminus has the nucleotide sequence 5' -ACTTTCGGCGGAGGGACCAAGGTGGAG-3' (SEQ ID NO
28) or 5' -ACTTTCGGCGGAGGGACC-3' (SEQ ID NO 29), or an oligonucleotide having a sequence complementary thereto.
28) or 5' -ACTTTCGGCGGAGGGACC-3' (SEQ ID NO 29), or an oligonucleotide having a sequence complementary thereto.
17. The method of claim 14 wherein n is 4, 5, 6, 10 or 16.
18. The method of claim 14 wherein said immunoglobulin is human.
19. The method of claim 14 wherein said CDR is CDR3.
20. The method of claim 14 according to the formula:
5'-GATTTTGCAGTGTATTACTGT [NNK]10TTCGGCGGAGGGCCAAGGTGGAG-3' (SEQ ID NO
12), or an oligonucleotide having a sequence complementary thereto.
5'-GATTTTGCAGTGTATTACTGT [NNK]10TTCGGCGGAGGGCCAAGGTGGAG-3' (SEQ ID NO
12), or an oligonucleotide having a sequence complementary thereto.
21. The method of claim 14 wherein said immunoglobulin light chain gene includes a sequence having the sequence characteristics of the light chain shown in SEQ ID NO 2 or in SEQ
ID NO 62.
ID NO 62.
22. The method of claim 14 wherein said immunoglobulin light chain gene has the sequence characteristics of the light chain gene in ATCC Accession No. 75408.
23. The method of claim 14 that further comprises the steps of:
a) isolating the amplified CDR to form a library of mutagenized immunoglobulin light chain genes;
b) expressing the isolated library of mutagenized light chain genes in combination with one or more heavy chain genes to form a combinatorial antibody library of expressed heavy and light chain genes; and c) selecting species of said combinatorial antibody library for the ability to bind a preselected antigen.
a) isolating the amplified CDR to form a library of mutagenized immunoglobulin light chain genes;
b) expressing the isolated library of mutagenized light chain genes in combination with one or more heavy chain genes to form a combinatorial antibody library of expressed heavy and light chain genes; and c) selecting species of said combinatorial antibody library for the ability to bind a preselected antigen.
24. The method of claim 23 wherein said one or more immunoglobulin heavy chain genes is a library of heavy chain genes.
25. A method for producing an antibody combining site in a polypeptide comprising inducing mutagenesis in a complementarity determining region (CDR) of an immunoglobulin light chain gene which comprises amplifying a CDR portion of the immunoglobulin gene by polymerase chain reaction (PCR) using a PCR primer oligonucleotide, said oligonucleotide having 3' and 5' termini and comprising:
a) a nucleotide sequence at said 3' terminus capable of hybridizing to a first framework region of an immunoglobulin gene;
b) a nucleotide sequence at said 5' terminus capable of hybridizing to a second framework region of an immunoglobulin gene; and c) a nucleotide sequence between said 3' and 5' termini according to the formula:
[MNN]n, wherein N is independently any nucleotide, M is A or C, n is 3 to about 24, said 3' and 5' terminal nucleotide sequences having a length of about 6 to 50 nucleotides, or an oligonucleotide having a sequence complementary thereto.
a) a nucleotide sequence at said 3' terminus capable of hybridizing to a first framework region of an immunoglobulin gene;
b) a nucleotide sequence at said 5' terminus capable of hybridizing to a second framework region of an immunoglobulin gene; and c) a nucleotide sequence between said 3' and 5' termini according to the formula:
[MNN]n, wherein N is independently any nucleotide, M is A or C, n is 3 to about 24, said 3' and 5' terminal nucleotide sequences having a length of about 6 to 50 nucleotides, or an oligonucleotide having a sequence complementary thereto.
26. The method of claim 25 wherein said 5' terminus has the nucleotide sequence 5'-GTTCCACCTTGGTCCCTTGGCCGAA-3' (SEQ ID NO
30), or an oligonucleotide having a sequence complementary thereto.
30), or an oligonucleotide having a sequence complementary thereto.
27. The method of claim 25 wherein said 3' terminus has the nucleotide sequence 5'-ACAGTAGTACACTGCAAAATC-3' (SEQ ID NO 31), or an oligonucleotide having a sequence complementary thereto.
28. The method of claim 25 wherein n is 8, 10 or 16.
29. The method of claim 25 wherein said immunoglobulin is human.
30. The method of claim 25 wherein said CDR is CDR3.
31. The method of claim 25 wherein said immunoglobulin light chain gene includes a sequence having the sequence characteristics of the light chain shown in SEQ ID NO 2 or in SEQ
ID NO 62.
ID NO 62.
32. The method of claim 25 wherein said immunoglobulin light chain gene has the sequence characteristics of the light chain gene in ATCC Accession No. 75408.
33. The method of claim 25 that further comprises the steps of:
a) isolating the amplified CDR to form a library of mutagenized immunoglobulin light chain genes;
b) expressing the isolated library of mutagenized light chain genes in combination with one or more heavy chain genes to form a combinatorial antibody library of expressed heavy and light chain genes; and c) selecting species of said combinatorial antibody library for the ability to bind a preselected antigen.
a) isolating the amplified CDR to form a library of mutagenized immunoglobulin light chain genes;
b) expressing the isolated library of mutagenized light chain genes in combination with one or more heavy chain genes to form a combinatorial antibody library of expressed heavy and light chain genes; and c) selecting species of said combinatorial antibody library for the ability to bind a preselected antigen.
34. The method of claim 33 wherein said one or more immunoglobulin heavy chain genes is a library of heavy chain genes.
35. A method for producing a heterodimeric immunoglobulin molecule having immunoglobulin variable domain heavy and light chain polypeptides comprising the steps of:
a) combining an immunoglobulin variable domain light chain gene that includes a sequence having the sequence characteristics of the light chain shown in SEQ ID NO 2 or 62 with one or more immunoglobulin variable domain heavy chain genes to form a combinatorial immunoglobulin heavy and light chain gene library, said combining comprising operatively linking said light chain gene with one of said heavy chain genes in a vector capable of co-expression of said heavy and light chain genes;
b) expressing the combinatorial gene library to form a combinatorial antibody library of expressed heavy and light chain polypeptides; and c) selecting species of said combinatorial antibody library for the ability to bind a preselected antigen.
a) combining an immunoglobulin variable domain light chain gene that includes a sequence having the sequence characteristics of the light chain shown in SEQ ID NO 2 or 62 with one or more immunoglobulin variable domain heavy chain genes to form a combinatorial immunoglobulin heavy and light chain gene library, said combining comprising operatively linking said light chain gene with one of said heavy chain genes in a vector capable of co-expression of said heavy and light chain genes;
b) expressing the combinatorial gene library to form a combinatorial antibody library of expressed heavy and light chain polypeptides; and c) selecting species of said combinatorial antibody library for the ability to bind a preselected antigen.
36. The method of claim 35 wherein said immunoglobulin light chain gene has the sequence characteristics of the light chain gene in ATCC Accession No. 75408.
37. The method of claim 35 wherein said one or more immunoglobulin heavy chain genes is a library of heavy chain genes.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/300,386 US5667988A (en) | 1992-01-27 | 1994-09-02 | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
US08/300,386 | 1994-09-02 | ||
PCT/US1995/011235 WO1996007754A1 (en) | 1994-09-02 | 1995-09-01 | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2198899A1 true CA2198899A1 (en) | 1996-03-14 |
CA2198899C CA2198899C (en) | 2010-02-23 |
Family
ID=23158889
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2198899A Expired - Lifetime CA2198899C (en) | 1994-09-02 | 1995-09-01 | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
Country Status (11)
Country | Link |
---|---|
US (2) | US5667988A (en) |
EP (1) | EP0779933B1 (en) |
JP (1) | JPH10504970A (en) |
AT (1) | ATE236992T1 (en) |
AU (1) | AU706343B2 (en) |
CA (1) | CA2198899C (en) |
DE (1) | DE69530305T2 (en) |
DK (1) | DK0779933T3 (en) |
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Families Citing this family (356)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU6235294A (en) * | 1993-02-02 | 1994-08-29 | Scripps Research Institute, The | Methods for producing polypeptide binding sites |
US20060078561A1 (en) * | 1994-01-31 | 2006-04-13 | The Trustees Of Boston University | Polyclonal antibody libraries |
DK0744958T3 (en) | 1994-01-31 | 2003-10-20 | Univ Boston | Polyclonal antibody libraries |
EP0859841B1 (en) * | 1995-08-18 | 2002-06-19 | MorphoSys AG | Protein/(poly)peptide libraries |
US6017754A (en) * | 1995-08-24 | 2000-01-25 | Invitrogen Corporation | System for isolating and identifying eukaryotic cells transfected with genes and vectors, host cells and methods thereof |
FR2741892B1 (en) * | 1995-12-04 | 1998-02-13 | Pasteur Merieux Serums Vacc | METHOD FOR PREPARING A MULTI-COMBINED BANK OF ANTIBODY GENE EXPRESSION VECTORS, BANK AND COLICLONAL ANTIBODY EXPRESSION SYSTEMS |
US6696251B1 (en) | 1996-05-31 | 2004-02-24 | Board Of Trustees Of The University Of Illinois | Yeast cell surface display of proteins and uses thereof |
GB9701425D0 (en) * | 1997-01-24 | 1997-03-12 | Bioinvent Int Ab | A method for in vitro molecular evolution of protein function |
US6590079B2 (en) * | 1997-01-30 | 2003-07-08 | Ixsys, Incorporated | Anti-αvβ3 recombinant human antibodies, nucleic acids encoding same |
US6596850B1 (en) * | 1998-01-30 | 2003-07-22 | Ixsys, Incorporated | Anti-αv3β3 recombinant human antibodies, nucleic acids encoding same |
WO1998047343A2 (en) * | 1997-04-04 | 1998-10-29 | Biosite Diagnostics, Inc. | Antibodies or binding protein libraries displayed on phage, cells, or other replicatable genetic packages |
US6057098A (en) | 1997-04-04 | 2000-05-02 | Biosite Diagnostics, Inc. | Polyvalent display libraries |
GB9722131D0 (en) * | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
US6759243B2 (en) * | 1998-01-20 | 2004-07-06 | Board Of Trustees Of The University Of Illinois | High affinity TCR proteins and methods |
EP1096955B9 (en) | 1998-07-13 | 2006-07-05 | Board of Regents, The University of Texas System | Uses of antibodies to aminophospholipids for cancer treatment |
AU5122499A (en) | 1998-07-27 | 2000-02-21 | Genentech Inc. | Improved transformation efficiency in phage display through modification of a coat protein |
US6531580B1 (en) * | 1999-06-24 | 2003-03-11 | Ixsys, Inc. | Anti-αvβ3 recombinant human antibodies and nucleic acids encoding same |
US6794132B2 (en) | 1999-10-02 | 2004-09-21 | Biosite, Inc. | Human antibodies |
US20070111259A1 (en) * | 1999-10-02 | 2007-05-17 | Medarex, Inc. | Human antibodies |
US7135287B1 (en) | 1999-10-02 | 2006-11-14 | Biosite, Inc. | Human antibodies |
US6849425B1 (en) | 1999-10-14 | 2005-02-01 | Ixsys, Inc. | Methods of optimizing antibody variable region binding affinity |
US6680209B1 (en) * | 1999-12-06 | 2004-01-20 | Biosite, Incorporated | Human antibodies as diagnostic reagents |
AU784983B2 (en) * | 1999-12-15 | 2006-08-17 | Genentech Inc. | Shotgun scanning, a combinatorial method for mapping functional protein epitopes |
US7229619B1 (en) | 2000-11-28 | 2007-06-12 | Medimmune, Inc. | Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment |
US6656467B2 (en) * | 2000-01-27 | 2003-12-02 | Medimmune, Inc. | Ultra high affinity neutralizing antibodies |
ES2390761T3 (en) | 2000-03-01 | 2012-11-16 | Medimmune, Llc | Recombinant high-potency antibodies and method for their production |
UA81743C2 (en) | 2000-08-07 | 2008-02-11 | Центокор, Инк. | HUMAN MONOCLONAL ANTIBODY WHICH SPECIFICALLY BINDS TUMOR NECROSIS FACTOR ALFA (TNFα), PHARMACEUTICAL MIXTURE CONTAINING THEREOF, AND METHOD FOR TREATING ARTHRITIS |
US7288390B2 (en) | 2000-08-07 | 2007-10-30 | Centocor, Inc. | Anti-dual integrin antibodies, compositions, methods and uses |
US6902734B2 (en) | 2000-08-07 | 2005-06-07 | Centocor, Inc. | Anti-IL-12 antibodies and compositions thereof |
US7198924B2 (en) | 2000-12-11 | 2007-04-03 | Invitrogen Corporation | Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites |
US6855493B2 (en) | 2000-11-28 | 2005-02-15 | Medimmune, Inc. | Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment |
US7179900B2 (en) * | 2000-11-28 | 2007-02-20 | Medimmune, Inc. | Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment |
US6818216B2 (en) | 2000-11-28 | 2004-11-16 | Medimmune, Inc. | Anti-RSV antibodies |
US7087726B2 (en) | 2001-02-22 | 2006-08-08 | Genentech, Inc. | Anti-interferon-α antibodies |
JP2004533840A (en) * | 2001-07-06 | 2004-11-11 | ジェネンテック・インコーポレーテッド | PDZ domain ligand by phage display |
US20030104604A1 (en) * | 2001-08-03 | 2003-06-05 | Weiping Yang | Genetically engineered bacterial strains for the display of foreign peptides on filamentous phage |
CA2467836A1 (en) | 2001-11-20 | 2003-09-04 | Duke University | Interfacial biomaterials |
GB0202206D0 (en) * | 2002-01-31 | 2002-03-20 | Bioinvent Int Ab | Method of making libraries of anti-ligands |
US7504364B2 (en) * | 2002-03-01 | 2009-03-17 | Receptors Llc | Methods of making arrays and artificial receptors |
US7244592B2 (en) | 2002-03-07 | 2007-07-17 | Dyax Corp. | Ligand screening and discovery |
MXPA04010215A (en) * | 2002-04-17 | 2005-03-07 | Crea Roberto | Universal libraries for immunoglobulins. |
US7405062B2 (en) * | 2002-05-14 | 2008-07-29 | San Diego Antibody | Method for cloning variable domain sequences of immunological gene repertoire |
EP1513879B1 (en) * | 2002-06-03 | 2018-08-22 | Genentech, Inc. | Synthetic antibody phage libraries |
US7425618B2 (en) * | 2002-06-14 | 2008-09-16 | Medimmune, Inc. | Stabilized anti-respiratory syncytial virus (RSV) antibody formulations |
US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
BR0312692A (en) | 2002-07-15 | 2007-06-26 | Univ Texas | selected antibodies and duramycin peptides that bind to anionic phospholipids and aminophospholipids and their uses in the treatment of viral infections and cancer |
ES2368733T3 (en) * | 2002-07-18 | 2011-11-21 | Merus B.V. | RECOMBINANT PRODUCTION OF MIXTURES OF ANTIBODIES. |
USRE47770E1 (en) | 2002-07-18 | 2019-12-17 | Merus N.V. | Recombinant production of mixtures of antibodies |
CA2494485A1 (en) * | 2002-07-25 | 2004-02-05 | Medimmune, Inc. | Methods of treating and preventing rsv, hmpv, and piv using anti-rsv, anti-hmpv, and anti-piv antibodies |
US20040067532A1 (en) | 2002-08-12 | 2004-04-08 | Genetastix Corporation | High throughput generation and affinity maturation of humanized antibody |
US20050037428A1 (en) * | 2002-09-16 | 2005-02-17 | Receptors Llc | Artificial receptors including reversibly immobilized building blocks, the building blocks, and methods |
US20040137481A1 (en) * | 2002-09-16 | 2004-07-15 | Receptors Llc | Artificial receptor building blocks, components, and kits |
US20050136483A1 (en) * | 2003-09-03 | 2005-06-23 | Receptors Llc | Nanodevices employing combinatorial artificial receptors |
US20050170385A1 (en) * | 2002-09-16 | 2005-08-04 | Receptors Llc | Artificial receptors including gradients |
US20050037381A1 (en) * | 2002-09-16 | 2005-02-17 | Receptors Llc | Artificial receptors, building blocks, and methods |
US20060057625A1 (en) * | 2002-09-16 | 2006-03-16 | Carlson Robert E | Scaffold-based artificial receptors and methods |
US20050037429A1 (en) * | 2003-03-28 | 2005-02-17 | Receptors Llc | Artificial receptors including reversibly immobilized building blocks and methods |
US7469076B2 (en) * | 2003-09-03 | 2008-12-23 | Receptors Llc | Sensors employing combinatorial artificial receptors |
EP1551876B1 (en) | 2002-10-16 | 2011-03-16 | Purdue Pharma L.P. | Antibodies that bind cell-associated ca 125/0722p and methods of use thereof |
US7427469B2 (en) * | 2002-11-05 | 2008-09-23 | Institut Pasteur | Method of treating cytomegalovirus with DC-SIGN blockers |
AU2003301804A1 (en) * | 2002-11-05 | 2004-06-07 | Institut National De La Sante Et De La Recherche Medicale | Dc-sign blockers and their use for preventing or treating viral infections. |
EP1629090B1 (en) * | 2002-11-06 | 2014-03-05 | iBio, Inc. | Expression of foreign sequences in plants using trans-activation system |
US7692063B2 (en) * | 2002-11-12 | 2010-04-06 | Ibio, Inc. | Production of foreign nucleic acids and polypeptides in sprout systems |
US7683238B2 (en) * | 2002-11-12 | 2010-03-23 | iBio, Inc. and Fraunhofer USA, Inc. | Production of pharmaceutically active proteins in sprouted seedlings |
AU2004205631A1 (en) * | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
EP1594956A4 (en) | 2003-02-03 | 2007-08-01 | Fraunhofer Usa Inc | System for expression of genes in plants |
US20050008625A1 (en) * | 2003-02-13 | 2005-01-13 | Kalobios, Inc. | Antibody affinity engineering by serial epitope-guided complementarity replacement |
EP2184298A1 (en) | 2003-03-14 | 2010-05-12 | Wyeth a Corporation of the State of Delaware | Antibodies against human IL-21 receptor and uses therefor |
EP1613737A4 (en) * | 2003-03-28 | 2008-12-03 | Receptors Llc | Artificial receptors including reversibly immobilized building blocks and methods |
AU2004272972A1 (en) | 2003-05-22 | 2005-03-24 | Fraunhofer Usa, Inc. | Recombinant carrier molecule for expression, delivery and purification of target polypeptides |
US9708410B2 (en) | 2003-05-30 | 2017-07-18 | Janssen Biotech, Inc. | Anti-tissue factor antibodies and compositions |
CA2527694C (en) | 2003-05-30 | 2015-07-14 | Hendricus Renerus Jacobus Mattheus Hoogenboom | Fab library for the preparation of anti vegf and anti rabies virus fabs |
US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
CA2542232A1 (en) | 2003-06-09 | 2005-01-20 | Alnylam Pharmaceuticals, Inc. | Method for treating neurodegenerative disease by inhibiting alpha-synuclein |
WO2005011580A2 (en) * | 2003-07-25 | 2005-02-10 | Board Of Regents, The University Of Texas System | Compositions and methods for herpes simplex prophylaxis and treatment |
KR20060069825A (en) * | 2003-08-01 | 2006-06-22 | 제넨테크, 인크. | Antibody cdr polypeptide sequences with restricted diversity |
US20070274988A1 (en) * | 2003-10-10 | 2007-11-29 | Five Prime Therapeautics, Inc. | Kiaa0779, Splice Variants Thereof, and Methods of Their Use |
US7329725B1 (en) * | 2003-10-29 | 2008-02-12 | Nastech Pharmaceutical Company Inc. | Phage displayed Trp cage ligands |
EP2287341B1 (en) | 2003-12-01 | 2013-02-13 | Life Technologies Corporation | Nucleic acid molecules containing recombination sites and methods of using the same |
AU2005207003C1 (en) | 2004-01-20 | 2013-06-13 | Humanigen, Inc. | Antibody specificity transfer using minimal essential binding determinants |
EP1737971B1 (en) | 2004-01-20 | 2017-08-16 | Merus N.V. | Mixtures of binding proteins |
EP1769068B1 (en) * | 2004-02-20 | 2014-12-31 | iBio, Inc. | Systems and methods for clonal expression in plants |
US7785903B2 (en) * | 2004-04-09 | 2010-08-31 | Genentech, Inc. | Variable domain library and uses |
EP1789453A2 (en) * | 2004-05-18 | 2007-05-30 | Genentech, Inc. | M13 virus major coat protein variants for c-terminal and bi-terminal display of a heterologous protein |
EP2255832A3 (en) | 2004-06-16 | 2011-02-09 | Affinergy, Inc. | IFBM's to promote attachment of target analytes |
MX2007000103A (en) * | 2004-07-06 | 2007-05-11 | Bioren Inc | Universal antibody libraries. |
CA2576195A1 (en) * | 2004-08-05 | 2006-02-16 | Biosite Incorporated | Compositions and methods for phage display of polypeptides |
WO2006029234A1 (en) * | 2004-09-03 | 2006-03-16 | Receptors Llc | Combinatorial artificial receptors including tether building blocks |
WO2006029383A2 (en) * | 2004-09-11 | 2006-03-16 | Receptors Llc | Combinatorial artificial receptors including peptide building blocks |
EP1812068A4 (en) * | 2004-10-29 | 2010-06-09 | Medimmune Inc | Methods of preventing and treating rsv infections and related conditions |
US10011858B2 (en) | 2005-03-31 | 2018-07-03 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing polypeptides by regulating polypeptide association |
DK2824183T3 (en) * | 2005-04-08 | 2020-09-28 | Chugai Pharmaceutical Co Ltd | Process for the production of bispecific antibodies |
CN102441163A (en) | 2005-05-27 | 2012-05-09 | 比奥根艾迪克Ma公司 | Tweak binding antibodies |
EP1919504B1 (en) * | 2005-08-03 | 2013-10-16 | iBio, Inc. | Antibody to bacillus anthracis protective antigen |
IL172297A (en) | 2005-10-03 | 2016-03-31 | Compugen Ltd | Soluble vegfr-1 variants for diagnosis of preeclamsia |
EP1945262A2 (en) * | 2005-10-20 | 2008-07-23 | The Scripps Research Institute | Fc labeling for immunostaining and immunotargeting |
ES2577292T3 (en) | 2005-11-07 | 2016-07-14 | Genentech, Inc. | Binding polypeptides with diversified VH / VL hypervariable sequences and consensus |
JP2009515516A (en) * | 2005-11-14 | 2009-04-16 | バイオレン・インク | Superhumanization of antibodies by blasting of putative mature CDRs and generation and screening of cohort libraries |
EP1951890A4 (en) | 2005-11-16 | 2009-06-24 | Ambrx Inc | Methods and compositions comprising non-natural amino acids |
US20070237764A1 (en) * | 2005-12-02 | 2007-10-11 | Genentech, Inc. | Binding polypeptides with restricted diversity sequences |
US7763245B2 (en) | 2005-12-15 | 2010-07-27 | Genentech, Inc. | Methods and compositions for targeting polyubiquitin |
RU2450020C2 (en) | 2006-01-05 | 2012-05-10 | Дженентек, Инк. | ANTI-EphB4 ANTIBODIES AND METHODS OF USING SAID ANTIBODIES |
EP2216339A1 (en) | 2006-01-16 | 2010-08-11 | Compugen Ltd. | Novel nucleotide and amino acid sequences, and methods of use thereof for diagnosis |
US20070186296A1 (en) * | 2006-02-02 | 2007-08-09 | Wyeth | Cloning, characterization, and application of tnfrsf19 in neurological disorders |
US8277816B2 (en) * | 2006-02-13 | 2012-10-02 | Fraunhofer Usa, Inc. | Bacillus anthracis antigens, vaccine compositions, and related methods |
JP2009526526A (en) * | 2006-02-13 | 2009-07-23 | フラウンホーファー ユーエスエー, インコーポレイテッド | Influenza antigens, vaccine compositions, and related methods |
US20080279877A1 (en) * | 2006-02-13 | 2008-11-13 | Fraunhofer U.S.A. Inc. | HPV antigens, vaccine compositions, and related methods |
AR059851A1 (en) | 2006-03-16 | 2008-04-30 | Genentech Inc | ANTIBODIES OF EGFL7 AND METHODS OF USE |
US7833724B2 (en) * | 2006-03-20 | 2010-11-16 | Teva Women's Health, Inc. | Methods for comparing the immunogenicity of products and uses thereof |
ES2654040T3 (en) | 2006-03-31 | 2018-02-12 | Chugai Seiyaku Kabushiki Kaisha | Antibody modification method for the purification of bispecific antibodies |
DK3056568T3 (en) | 2006-03-31 | 2021-11-01 | Chugai Pharmaceutical Co Ltd | PROCEDURES FOR CONTROL OF THE BLOOD PHARMACOKINETICS OF ANTIBODIES |
CA2651567A1 (en) * | 2006-05-09 | 2007-11-22 | Genentech, Inc. | Binding polypeptides with optimized scaffolds |
US8148085B2 (en) | 2006-05-15 | 2012-04-03 | Sea Lane Biotechnologies, Llc | Donor specific antibody libraries |
AU2007249160B2 (en) * | 2006-05-15 | 2013-09-12 | I2 Pharmaceuticals, Inc. | Neutralizing antibodies to influenza viruses |
AR060978A1 (en) | 2006-05-30 | 2008-07-23 | Genentech Inc | ANTIBODIES AND IMMUNOCATE PLAYERS AND THEIR USES |
AU2007319672B2 (en) | 2006-06-06 | 2011-06-30 | Genentech, Inc. | Anti-DLL4 antibodies and methods using same |
US20100003189A1 (en) | 2006-07-14 | 2010-01-07 | The Regents Of The University Of California | Cancer biomarkers and methods of use thereof |
US20090252745A1 (en) * | 2006-09-15 | 2009-10-08 | Duke University | Amino acids in the HCV core polypeptide domain 3 and correlation with steatosis |
EP2069558B1 (en) | 2006-10-02 | 2013-05-01 | Sea Lane Biotechnologies,llc. | Design and construction of diverse synthetic peptide and polypeptide libraries |
SI2502938T1 (en) | 2006-10-27 | 2015-05-29 | Genentech, Inc. | Antibodies and immunoconjugates and uses therefor |
WO2008086002A2 (en) | 2007-01-08 | 2008-07-17 | Government Of The Usa, As Represented By The Secretary, Department Of Health And Human Services | Slco1b3 genotype |
US9896511B2 (en) | 2007-01-10 | 2018-02-20 | The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services | Antibodies that bind to TL1A and methods of treating inflammatory or autoimmune disease comprising administering such antibodies |
US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
WO2008134643A2 (en) * | 2007-04-28 | 2008-11-06 | Fraunhofer Usa, Inc. | Trypanosoma antigens, vaccine compositions, and related methods |
EP1997830A1 (en) * | 2007-06-01 | 2008-12-03 | AIMM Therapeutics B.V. | RSV specific binding molecules and means for producing them |
WO2009009759A2 (en) | 2007-07-11 | 2009-01-15 | Fraunhofer Usa, Inc. | Yersinia pestis antigens, vaccine compositions, and related methods |
JP5469600B2 (en) | 2007-07-16 | 2014-04-16 | ジェネンテック, インコーポレイテッド | Anti-CD79b antibody and immunoconjugate and method of use thereof |
TW200918089A (en) | 2007-07-16 | 2009-05-01 | Genentech Inc | Humanized anti-CD79b antibodies and immunoconjugates and methods of use |
US20110059130A1 (en) * | 2007-08-20 | 2011-03-10 | Fraunhofer Usa, Inc. | Prophylactic and therapeutic influenza vaccines, antigens, compositions and methods |
WO2009026496A1 (en) * | 2007-08-22 | 2009-02-26 | University Of Southern California | Grp78 and tumor angiogenesis |
EP2193146B1 (en) | 2007-09-14 | 2016-05-25 | Adimab, LLC | Rationally designed, synthetic antibody libraries and uses therefor |
US8877688B2 (en) | 2007-09-14 | 2014-11-04 | Adimab, Llc | Rationally designed, synthetic antibody libraries and uses therefor |
CN106519025B (en) | 2007-09-26 | 2021-04-23 | 中外制药株式会社 | Method for changing isoelectric point of antibody by using amino acid substitution of CDR |
JP5620106B2 (en) | 2007-10-24 | 2014-11-05 | 株式会社糖鎖工学研究所 | Polypeptide having enhanced effector function |
JP5809415B2 (en) | 2007-11-09 | 2015-11-10 | ペレグリン ファーマシューティカルズ,インコーポレーテッド | Compositions and methods of anti-VEGF antibodies |
AR069501A1 (en) | 2007-11-30 | 2010-01-27 | Genentech Inc | ANTI-VEGF ANTIBODIES (VASCULAR ENDOTELIAL GROWTH FACTOR) |
EP2247617B1 (en) | 2008-01-18 | 2013-02-27 | Genentech, Inc. | Methods and compositions for targeting polyubiquitin |
SI2657253T1 (en) | 2008-01-31 | 2017-10-30 | Genentech, Inc. | Anti-CD79b antibodies and immunoconjugates and methods of use |
KR102469853B1 (en) | 2008-04-11 | 2022-11-22 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
JP2011524858A (en) * | 2008-05-15 | 2011-09-08 | セレクシーズ ファーマスーティカルズ コーポレーション | Anti-PSGL-1 antibody and method for identification and use thereof |
US20090291073A1 (en) * | 2008-05-20 | 2009-11-26 | Ward Keith W | Compositions Comprising PKC-theta and Methods for Treating or Controlling Ophthalmic Disorders Using Same |
JP2009278908A (en) * | 2008-05-22 | 2009-12-03 | Fujifilm Corp | Anti-osteocalcin antibody and immunity-measuring method using the same |
MX2010014358A (en) | 2008-06-20 | 2011-07-04 | Wyeth Llc | Compositions and methods of use of orf1358 from beta-hemolytic streptococcal strains. |
JP5986745B2 (en) | 2008-07-15 | 2016-09-06 | アカデミア シニカAcademia Sinica | Glycan arrays on PTFE-like aluminum-coated glass slides and related methods |
NZ590330A (en) * | 2008-07-21 | 2012-08-31 | Immunomedics Inc | Structural variants of anti-cd20 antibodies for improved therapeutic characteristics |
US8563697B2 (en) | 2008-08-14 | 2013-10-22 | Cephalon Australia Pty. Ltd. | Anti-IL-12/IL-23 antibodies |
US8946291B2 (en) | 2008-08-15 | 2015-02-03 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Compositions and methods for treating pigmentary conditions and melanoma |
US20100093563A1 (en) * | 2008-09-22 | 2010-04-15 | Robert Anthony Williamson | Methods and vectors for display of molecules and displayed molecules and collections |
US20100081575A1 (en) * | 2008-09-22 | 2010-04-01 | Robert Anthony Williamson | Methods for creating diversity in libraries and libraries, display vectors and methods, and displayed molecules |
WO2010037046A1 (en) | 2008-09-28 | 2010-04-01 | Fraunhofer Usa, Inc. | Humanized neuraminidase antibody and methods of use thereof |
EP2341924A4 (en) | 2008-10-02 | 2013-01-23 | David Gladstone Inst | Methods of treating hepatitis c virus infection |
WO2010062995A2 (en) | 2008-11-26 | 2010-06-03 | Five Prime Therapeutics, Inc. | Compositions and methods for regulating collagen and smooth muscle actin expression by serpine2 |
WO2010061393A1 (en) | 2008-11-30 | 2010-06-03 | Compugen Ltd. | He4 variant nucleotide and amino acid sequences, and methods of use thereof |
CN101768213B (en) | 2008-12-30 | 2012-05-30 | 中国科学院遗传与发育生物学研究所 | Protein related to plant tillering number and coding gene and application thereof |
CN101817879A (en) | 2009-02-26 | 2010-09-01 | 中国科学院遗传与发育生物学研究所 | Metallothionein and encoding gene and application thereof |
CA2754163C (en) | 2009-03-25 | 2019-04-09 | Genentech, Inc. | Anti-fgfr3 antibodies and methods using same |
AU2010236787A1 (en) | 2009-04-01 | 2011-11-10 | Genentech, Inc. | Anti-FcRH5 antibodies and immunoconjugates and methods of use |
US20110033389A1 (en) * | 2009-04-29 | 2011-02-10 | Zhifeng Chen | Modified antibodies for passive immunotherapy |
CA2762837C (en) * | 2009-05-20 | 2021-08-03 | Novimmune S.A. | Synthetic polypeptide libraries and methods for generating naturally diversified polypeptide variants |
US8685896B2 (en) | 2009-05-29 | 2014-04-01 | Morphosys Ag | Collection and methods for its use |
TW201106972A (en) | 2009-07-27 | 2011-03-01 | Genentech Inc | Combination treatments |
US8568719B2 (en) | 2009-08-13 | 2013-10-29 | Crucell Holland B.V. | Antibodies against human respiratory syncytial virus (RSV) and methods of use |
US9321823B2 (en) | 2009-09-02 | 2016-04-26 | Genentech, Inc. | Mutant smoothened and methods of using the same |
US20110189183A1 (en) | 2009-09-18 | 2011-08-04 | Robert Anthony Williamson | Antibodies against candida, collections thereof and methods of use |
EP2483307A1 (en) | 2009-09-29 | 2012-08-08 | Fraunhofer USA, Inc. | Influenza hemagglutinin antibodies, compositions, and related methods |
US8568726B2 (en) | 2009-10-06 | 2013-10-29 | Medimmune Limited | RSV specific binding molecule |
NZ599337A (en) | 2009-10-22 | 2013-05-31 | Genentech Inc | Anti-hepsin antibodies and methods using same |
WO2011056497A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Activin receptor type iib compositions and methods of use |
WO2011056502A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Bone morphogenetic protein receptor type ii compositions and methods of use |
WO2011056494A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Activin receptor-like kinase-1 antagonist and vegfr3 antagonist combinations |
AU2010315101B2 (en) | 2009-11-04 | 2016-01-28 | Fabrus Llc | Methods for affinity maturation-based antibody optimization |
RU2585488C2 (en) | 2009-11-05 | 2016-05-27 | Дженентек, Инк. | Methods and composition for secretion of heterologous polypeptides |
US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
US11377485B2 (en) | 2009-12-02 | 2022-07-05 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
TWI505836B (en) | 2009-12-11 | 2015-11-01 | Genentech Inc | Anti-vegf-c antibodies and methods using same |
KR101989628B1 (en) | 2009-12-21 | 2019-06-14 | 제넨테크, 인크. | Antibody formulation |
SI2516465T1 (en) | 2009-12-23 | 2016-08-31 | F. Hoffmann-La Roche Ag | Anti-bv8 antibodies and uses thereof |
EP2530109A4 (en) | 2010-01-29 | 2013-08-28 | Toray Industries | Polylactic acid-based resin sheet |
US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
EP3095871B1 (en) | 2010-02-08 | 2019-04-10 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
WO2011130332A1 (en) | 2010-04-12 | 2011-10-20 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
EP3508854A1 (en) | 2010-04-27 | 2019-07-10 | The Regents of The University of California | Cancer biomarkers and methods of use thereof |
CA2835489C (en) | 2010-05-10 | 2018-03-06 | Chi-Huey Wong | Zanamivir phosphonate congeners with anti-influenza activity and determining oseltamivir susceptibility of influenza viruses |
BR112012029866A2 (en) | 2010-06-03 | 2017-03-07 | Genentech Inc | method for determining the presence of a steap-1 protein |
EA027835B1 (en) | 2010-07-09 | 2017-09-29 | Круселл Холланд Б.В. | Anti-human respiratory syncytial virus (rsv) antibodies and methods of use thereof |
WO2012019061A2 (en) | 2010-08-05 | 2012-02-09 | Stem Centrx, Inc. | Novel effectors and methods of use |
SG10201506782XA (en) | 2010-08-27 | 2015-10-29 | Stem Centrx Inc | Notum protein modulators and methods of use |
CN106620693A (en) | 2010-09-03 | 2017-05-10 | 艾伯维施特姆森特克斯有限责任公司 | Novel modulators and methods of use |
WO2012033953A1 (en) | 2010-09-08 | 2012-03-15 | Halozyme, Inc. | Methods for assessing and identifying or evolving conditionally active therapeutic proteins |
WO2012047968A2 (en) | 2010-10-05 | 2012-04-12 | Genentech, Inc. | Mutant smoothened and methods of using the same |
SG10202100921YA (en) | 2010-10-27 | 2021-03-30 | Univ New York State Res Found | Compositions targeting the soluble extracellular domain of e-cadherin and related methods for cancer therapy |
TR201802772T4 (en) | 2010-11-17 | 2018-03-21 | Chugai Pharmaceutical Co Ltd | Multi-specific antigen binding molecule with alternative function for the function of blood coagulation factor VIII. |
EP2640742B1 (en) | 2010-11-19 | 2018-08-15 | MorphoSys AG | A collection of antibody sequences its use |
EP2648748A1 (en) | 2010-12-08 | 2013-10-16 | Stem Centrx, Inc. | Novel modulators and methods of use |
WO2012092539A2 (en) | 2010-12-31 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Antibodies to dll4 and uses thereof |
SA112330278B1 (en) | 2011-02-18 | 2015-10-09 | ستيم سينتركس، انك. | Novel modulators and methods of use |
WO2012142662A1 (en) | 2011-04-21 | 2012-10-26 | Garvan Institute Of Medical Research | Modified variable domain molecules and methods for producing and using them b |
KR20140104344A (en) | 2011-05-20 | 2014-08-28 | 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 시크리터리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비시스 | Blockade of tl1a-dr3 interactions to ameliorate t cell mediated disease pathology and antibodies thereof |
MY172718A (en) | 2011-08-05 | 2019-12-11 | Regeneron Pharma | Humanized universal light chain mice |
US20130058947A1 (en) | 2011-09-02 | 2013-03-07 | Stem Centrx, Inc | Novel Modulators and Methods of Use |
DK2761006T3 (en) | 2011-09-28 | 2017-03-27 | Zera Intein Protein Solutions S L | Cleft inteins and uses thereof |
WO2013046960A1 (en) * | 2011-09-29 | 2013-04-04 | Necソフト株式会社 | Nucleic acid construct for use in screening for peptide antibody, and screening method using same |
WO2013047748A1 (en) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | Antigen-binding molecule promoting disappearance of antigens having plurality of biological activities |
CN109134658B (en) | 2011-10-31 | 2022-10-14 | 中外制药株式会社 | Antigen binding molecules that control association of heavy and light chains |
WO2013106489A1 (en) | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Humanized antibodies with ultralong cdr3s |
WO2013106485A2 (en) | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Ultralong complementarity determining regions and uses thereof |
DK2817338T3 (en) | 2012-02-24 | 2017-10-23 | Abbvie Stemcentrx Llc | DLL3 modulators and methods of use |
EP3296320A1 (en) | 2012-03-08 | 2018-03-21 | Halozyme, Inc. | Conditionally active anti-epidermal growth factor receptor antibodies and methods of use thereof |
US20140087362A1 (en) | 2012-03-16 | 2014-03-27 | Aladar A. Szalay | Methods for assessing effectiveness and monitoring oncolytic virus treatment |
US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
RU2014141536A (en) | 2012-03-16 | 2016-05-10 | Регенерон Фармасьютикалз, Инк. | MICE WHICH PRODUCE ANTIGEN-BINDING PROTEINS WITH PH-DEPENDENT BINDING CHARACTERISTICS |
CN107827979A (en) | 2012-03-16 | 2018-03-23 | 瑞泽恩制药公司 | The engineered light chain antibody of histidine and the non-human animal through genetic modification for generating the antibody |
SI2825037T1 (en) | 2012-03-16 | 2019-08-30 | Regeneron Pharmaceuticals, Inc. | Rodents expressing ph-sensitive immunoglobulin sequences |
US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
MX360109B (en) | 2012-04-20 | 2018-10-23 | Merus Nv | Methods and means for the production of ig-like molecules. |
DK2692865T3 (en) * | 2012-07-30 | 2015-02-16 | Nbe Therapeutics Llc | Transponeringsmedieret identification of specific binding proteins, or functional |
AU2013306098A1 (en) | 2012-08-18 | 2015-02-12 | Academia Sinica | Cell-permeable probes for identification and imaging of sialidases |
WO2014031762A1 (en) | 2012-08-21 | 2014-02-27 | Academia Sinica | Benzocyclooctyne compounds and uses thereof |
ES2780398T3 (en) | 2012-12-10 | 2020-08-25 | Biogen Ma Inc | Anti-blood dendritic cell antigen 2 antibody and use thereof |
US10717965B2 (en) | 2013-01-10 | 2020-07-21 | Gloriana Therapeutics, Inc. | Mammalian cell culture-produced neublastin antibodies |
MX2015010682A (en) | 2013-02-22 | 2016-05-31 | Stemcentrx Inc | Novel antibody conjugates and uses thereof. |
BR112015022210A8 (en) | 2013-03-13 | 2018-01-23 | Genentech Inc | antibody formulations |
CN110075293A (en) | 2013-03-13 | 2019-08-02 | 霍夫曼-拉罗奇有限公司 | Aoxidize reduced preparaton |
US10653779B2 (en) | 2013-03-13 | 2020-05-19 | Genentech, Inc. | Formulations with reduced oxidation |
HUE049707T2 (en) | 2013-03-13 | 2020-11-30 | Hoffmann La Roche | Formulations with reduced oxidation |
AR095398A1 (en) | 2013-03-13 | 2015-10-14 | Genentech Inc | FORMULATIONS WITH REDUCED OXIDATION |
WO2014145098A1 (en) | 2013-03-15 | 2014-09-18 | Genentech, Inc. | Cell culture compositions with antioxidants and methods for polypeptide production |
CA2903546A1 (en) | 2013-03-15 | 2014-09-25 | Biogen Ma Inc. | Treatment and prevention of acute kidney injury using anti-alpha v beta 5 antibodies |
US9441035B2 (en) | 2013-03-15 | 2016-09-13 | Genentech, Inc. | Cell culture media and methods of antibody production |
US10086054B2 (en) | 2013-06-26 | 2018-10-02 | Academia Sinica | RM2 antigens and use thereof |
EP3013347B1 (en) | 2013-06-27 | 2019-12-11 | Academia Sinica | Glycan conjugates and use thereof |
CN105814074B (en) | 2013-07-18 | 2020-04-21 | 图鲁斯生物科学有限责任公司 | Humanized antibodies with ultralong complementarity determining regions |
EP3022224A2 (en) | 2013-07-18 | 2016-05-25 | Fabrus, Inc. | Antibodies with ultralong complementarity determining regions |
EP3036320B2 (en) | 2013-08-19 | 2024-04-03 | Biogen MA Inc. | Control of protein glycosylation by culture medium supplementation and cell culture process parameters |
EP3892294A1 (en) | 2013-08-28 | 2021-10-13 | AbbVie Stemcentrx LLC | Site-specific antibody conjugation methods and compositions |
EP3338793A1 (en) | 2013-08-28 | 2018-06-27 | AbbVie Stemcentrx LLC | Novel sez6 modulators and methods of use |
CN105682666B (en) | 2013-09-06 | 2021-06-01 | 中央研究院 | Activation of human iNKT cells using glycolipids |
MX2016003256A (en) | 2013-09-12 | 2016-06-07 | Halozyme Inc | Modified anti-epidermal growth factor receptor antibodies and methods of use thereof. |
EP3048899B1 (en) | 2013-09-25 | 2021-09-08 | Bioverativ Therapeutics Inc. | On-column viral inactivation methods |
SG11201602283UA (en) | 2013-09-27 | 2016-04-28 | Genentech Inc | Anti-pdl1 antibody formulations |
BR112016006197B1 (en) | 2013-09-27 | 2023-04-11 | Chugai Seiyaku Kabushiki Kaisha | METHOD FOR PRODUCING A BISPECIFIC POLYPEPTIDE ANTIBODY |
AU2014349828B2 (en) | 2013-11-15 | 2021-01-28 | Centre National De La Recherche Scientifique | A molecular marker of Plasmodium falciparum artemisinin resistance |
JP2017500017A (en) | 2013-12-20 | 2017-01-05 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | Use of perfusion seed cultures to improve biopharmaceutical fed-batch production capacity and product quality |
EP2960252A1 (en) | 2014-06-26 | 2015-12-30 | Institut Pasteur | Phospholipase for treatment of immunosuppression |
PL3712174T3 (en) | 2013-12-24 | 2022-07-04 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments |
US10238700B2 (en) | 2014-01-02 | 2019-03-26 | Genelux Corporation | Oncolytic virus adjunct therapy with agents that increase virus infectivity |
WO2016114819A1 (en) | 2015-01-16 | 2016-07-21 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
US9982041B2 (en) | 2014-01-16 | 2018-05-29 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
WO2015120075A2 (en) | 2014-02-04 | 2015-08-13 | Genentech, Inc. | Mutant smoothened and methods of using the same |
JP2017514143A (en) | 2014-02-21 | 2017-06-01 | アッヴィ・ステムセントルクス・エル・エル・シー | Anti-DLL3 antibodies and drug conjugates for use in melanoma |
SG11201607203XA (en) | 2014-03-21 | 2016-09-29 | Regeneron Pharma | Non-human animals that make single domain binding proteins |
EP3122869B2 (en) | 2014-03-24 | 2022-08-10 | Biogen MA Inc. | Methods for overcoming glutamine deprivation during mammalian cell culture |
TWI687428B (en) | 2014-03-27 | 2020-03-11 | 中央研究院 | Reactive labelling compounds and uses thereof |
DK3126384T3 (en) | 2014-04-01 | 2021-01-18 | Adimab Llc | MULTISPECIFIC ANTIBODY ANALOGS INCLUDING A COMMON LIGHT CHAIN, AND METHODS FOR THEIR PREPARATION AND USE |
CA2946606C (en) | 2014-05-13 | 2023-06-06 | Bavarian Nordic A/S | Combination therapy for treating cancer with a poxvirus expressing a tumor antigen and an antagonist of tim-3 |
CN106573971A (en) | 2014-05-27 | 2017-04-19 | 中央研究院 | Anti-CD20 glycoantibodies and uses thereof |
US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
AU2015267045B2 (en) | 2014-05-27 | 2021-02-25 | Academia Sinica | Anti-HER2 glycoantibodies and uses thereof |
EP3149161B1 (en) | 2014-05-27 | 2021-07-28 | Academia Sinica | Fucosidase from bacteroides and methods using the same |
TWI732738B (en) | 2014-05-28 | 2021-07-11 | 中央研究院 | Anti-tnf-alpha glycoantibodies and uses thereof |
TWI695011B (en) | 2014-06-18 | 2020-06-01 | 美商梅爾莎納醫療公司 | Monoclonal antibodies against her2 epitope and methods of use thereof |
EP3186281B1 (en) | 2014-08-28 | 2019-04-10 | Halozyme, Inc. | Combination therapy with a hyaluronan-degrading enzyme and an immune checkpoint inhibitor |
WO2016040369A2 (en) | 2014-09-08 | 2016-03-17 | Academia Sinica | HUMAN iNKT CELL ACTIVATION USING GLYCOLIPIDS |
BR112017004393A2 (en) | 2014-09-15 | 2018-02-27 | Genentech Inc | antibody formulations |
TWI700300B (en) | 2014-09-26 | 2020-08-01 | 日商中外製藥股份有限公司 | Antibodies that neutralize substances with the function of FVIII coagulation factor (FVIII) |
MA40764A (en) | 2014-09-26 | 2017-08-01 | Chugai Pharmaceutical Co Ltd | THERAPEUTIC AGENT INDUCING CYTOTOXICITY |
TWI701435B (en) | 2014-09-26 | 2020-08-11 | 日商中外製藥股份有限公司 | Method to determine the reactivity of FVIII |
MA41685A (en) | 2014-10-17 | 2017-08-22 | Biogen Ma Inc | COPPER SUPPLEMENT FOR THE REGULATION OF GLYCOSYLATION IN A MAMMAL CELL CULTURE PROCESS |
MA40864A (en) | 2014-10-31 | 2017-09-05 | Biogen Ma Inc | HYPOTAURINE, GABA, BETA-ALANINE AND CHOLINE FOR THE REGULATION OF THE ACCUMULATION OF RESIDUAL BY-PRODUCTS IN MAMMAL CELL CULTURE PROCESSES |
CA2961439A1 (en) | 2014-11-05 | 2016-05-12 | Genentech, Inc. | Anti-fgfr2/3 antibodies and methods using same |
ES2832802T3 (en) | 2014-11-21 | 2021-06-11 | Univ Maryland | Systems of directed administration of the specific particulate of a structure |
US11543411B2 (en) | 2014-12-05 | 2023-01-03 | Prelude Corporation | DCIS recurrence and invasive breast cancer |
US9975965B2 (en) | 2015-01-16 | 2018-05-22 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
US10495645B2 (en) | 2015-01-16 | 2019-12-03 | Academia Sinica | Cancer markers and methods of use thereof |
EP3248005B1 (en) | 2015-01-24 | 2020-12-09 | Academia Sinica | Novel glycan conjugates and methods of use thereof |
WO2016118961A1 (en) | 2015-01-24 | 2016-07-28 | Academia Sinica | Cancer markers and methods of use thereof |
AU2016211176B2 (en) | 2015-01-30 | 2021-01-28 | Academia Sinica; | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
CA3185253A1 (en) | 2015-02-02 | 2016-08-11 | Children's Health Care D/B/A Children's Minnesota | Anti-surrogate light chain antibodies |
US10330683B2 (en) | 2015-02-04 | 2019-06-25 | Genentech, Inc. | Mutant smoothened and methods of using the same |
CA2979702A1 (en) | 2015-03-19 | 2016-09-22 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
EP3279216A4 (en) | 2015-04-01 | 2019-06-19 | Chugai Seiyaku Kabushiki Kaisha | Method for producing polypeptide hetero-oligomer |
EP3280444A4 (en) | 2015-04-10 | 2019-03-27 | Adimab, LLC | Methods for purifying heterodimeric multispecific antibodies from parental homodimeric antibody species |
US10954515B2 (en) | 2015-04-21 | 2021-03-23 | Institut Gustave Roussy | Therapeutic methods, products and compositions inhibiting ZNF555 |
JP7026509B2 (en) | 2015-06-24 | 2022-02-28 | ヤンセン ファーマシューティカ エヌブイ | Anti-VISTA antibody and fragment |
TWI797060B (en) | 2015-08-04 | 2023-04-01 | 美商再生元醫藥公司 | Taurine supplemented cell culture medium and methods of use |
WO2017041027A1 (en) | 2015-09-04 | 2017-03-09 | Obi Pharma, Inc. | Glycan arrays and method of use |
WO2017115773A1 (en) | 2015-12-28 | 2017-07-06 | 中外製薬株式会社 | Method for promoting efficiency of purification of fc region-containing polypeptide |
EP3397287A1 (en) | 2015-12-30 | 2018-11-07 | Genentech, Inc. | Formulations with reduced degradation of polysorbate |
CN108430455A (en) | 2015-12-30 | 2018-08-21 | 豪夫迈·罗氏有限公司 | Tryptophan derivative is used for the purposes of protein preparaton |
CA3019952A1 (en) | 2016-02-04 | 2017-08-10 | Curis, Inc. | Mutant smoothened and methods of using the same |
CN116920085A (en) | 2016-02-12 | 2023-10-24 | 詹森药业有限公司 | anti-VISTA (B7H 5) antibodies |
TW201808978A (en) | 2016-03-08 | 2018-03-16 | 中央研究院 | Methods for modular synthesis of N-glycans and arrays thereof |
US10947317B2 (en) | 2016-03-15 | 2021-03-16 | Mersana Therapeutics, Inc. | NaPi2b-targeted antibody-drug conjugates and methods of use thereof |
WO2017161206A1 (en) | 2016-03-16 | 2017-09-21 | Halozyme, Inc. | Conjugates containing conditionally active antibodies or antigen-binding fragments thereof, and methods of use |
EP3433377A4 (en) | 2016-03-23 | 2019-08-28 | The General Hospital Corporation | Assays and methods for detecting udp-glucose |
KR20180121786A (en) | 2016-03-29 | 2018-11-08 | 오비아이 파머 인코퍼레이티드 | Antibodies, pharmaceutical compositions and methods |
AU2017241776A1 (en) | 2016-03-29 | 2018-10-11 | Janssen Biotech, Inc. | Treating psoriasis with increased interval dosing of anti-IL12 and/or -23 antibody |
US10980894B2 (en) | 2016-03-29 | 2021-04-20 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
PT3440208T (en) | 2016-04-06 | 2020-12-04 | Zumutor Biologics Inc | Vectors for cloning and expression of proteins, methods and applications thereof |
WO2017175058A1 (en) | 2016-04-07 | 2017-10-12 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
KR20230110820A (en) | 2016-04-22 | 2023-07-25 | 오비아이 파머 인코퍼레이티드 | Cancer immunotherapy by immune activation or immune modulation via globo series antigens |
US20190330318A1 (en) | 2016-07-25 | 2019-10-31 | Biogen Ma Inc. | Anti-hspa5 (grp78) antibodies and uses thereof |
CN110072545A (en) | 2016-07-27 | 2019-07-30 | 台湾浩鼎生技股份有限公司 | Immunogenicity/therapeutic glycan pool object and application thereof |
KR102528998B1 (en) | 2016-07-29 | 2023-05-03 | 오비아이 파머 인코퍼레이티드 | Human Antibodies, Pharmaceutical Compositions and Methods |
JP7213549B2 (en) | 2016-08-22 | 2023-01-27 | シーエイチオー ファーマ インコーポレイテッド | Antibodies, Binding Fragments, and Methods of Use |
CA3035327A1 (en) | 2016-09-06 | 2018-03-15 | Chugai Seiyaku Kabushiki Kaisha | Methods of using a bispecific antibody that recognizes coagulation factor ix and/or activated coagulation factor ix and coagulation factor x and/or activated coagulation factor x |
MX2019003703A (en) | 2016-09-30 | 2020-08-13 | Janssen Biotech Inc | Safe and effective method of treating psoriasis with anti-il23 specific antibody. |
AU2017362222A1 (en) | 2016-11-16 | 2019-05-30 | Janssen Biotech, Inc. | Method of treating psoriasis with anti-IL-23 specific antibody |
JP2019535731A (en) | 2016-11-21 | 2019-12-12 | オービーアイ ファーマ,インコーポレイテッド | Conjugated biological molecules, pharmaceutical compositions and methods |
CA3052095A1 (en) | 2017-01-30 | 2018-08-02 | Janssen Biotech, Inc. | Anti-tnf antibodies, compositions, and methods for the treatment of active psoriatic arthritis |
MA47442A (en) | 2017-02-07 | 2019-12-18 | Janssen Biotech Inc | ANTI-TNF ANTIBODIES, COMPOSITIONS AND METHODS FOR THE TREATMENT OF ACTIVE ANKYLOSING SPONDYLARTHRITIS |
TW201922780A (en) | 2017-09-25 | 2019-06-16 | 美商健生生物科技公司 | Safe and effective method of treating Lupus with anti-IL12/IL23 antibody |
MX2020002710A (en) | 2017-09-29 | 2020-07-20 | Chugai Pharmaceutical Co Ltd | Multispecific antigen-binding molecule having blood coagulation factor viii (fviii) cofactor function-substituting activity, and pharmaceutical formulation containing said molecule as active ingredient. |
WO2019150309A1 (en) | 2018-02-02 | 2019-08-08 | Hammack Scott | Modulators of gpr68 and uses thereof for treating and preventing diseases |
EP3530282A1 (en) | 2018-02-27 | 2019-08-28 | Diaccurate | Therapeutic methods |
JP2021515770A (en) | 2018-03-05 | 2021-06-24 | ヤンセン バイオテツク,インコーポレーテツド | Treatment of Crohn's disease using anti-IL-23 specific antibody |
BR112020018235A2 (en) * | 2018-03-14 | 2020-12-29 | F. Hoffmann-La Roche Ag | METHODS FOR GENERATING A POLYNUCLEOTIDE LIBRARY, POLYNUCLEOTIDE LIBRARIES, USE OF A LIBRARY, METHOD FOR GENERATING AN ANTIBODY LIBRARY AND METHOD OF SELECTING AN ANTIBODY |
US11203645B2 (en) | 2018-06-27 | 2021-12-21 | Obi Pharma, Inc. | Glycosynthase variants for glycoprotein engineering and methods of use |
WO2020016838A2 (en) | 2018-07-18 | 2020-01-23 | Janssen Biotech, Inc. | Sustained response predictors after treatment with anti-il23 specific antibody |
BR112021002130A2 (en) | 2018-08-08 | 2021-05-04 | Genentech, Inc. | liquid formulation, article of manufacture or kit and method for reducing oxidation of a polypeptide |
WO2020056338A1 (en) | 2018-09-14 | 2020-03-19 | Prelude Corporation | Method of selection for treatment of subjects at risk of invasive breast cancer |
DK3883606T5 (en) | 2018-09-24 | 2024-01-02 | Janssen Biotech Inc | SAFE AND EFFECTIVE METHOD FOR TREATMENT OF ULCERATIVE COLITIS WITH ANTI-IL12/IL23 ANTIBODY |
JP2022512595A (en) | 2018-10-05 | 2022-02-07 | バヴァリアン・ノルディック・アクティーゼルスカブ | Combination therapy to treat cancer by intravenous administration of recombinant MVA and immune checkpoint antagonists or immune checkpoint agonists |
WO2020086408A1 (en) | 2018-10-26 | 2020-04-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A high-yield perfusion-based transient gene expression bioprocess |
WO2020104943A2 (en) | 2018-11-20 | 2020-05-28 | Janssen Biotech, Inc. | Safe and effective method of treating psoriasis with anti-il-23 specific antibody |
CA3119503A1 (en) | 2018-11-20 | 2020-05-28 | Bavarian Nordic A/S | Therapy for treating cancer with an intratumoral and/or intravenous administration of a recombinant mva encoding 4-1bbl (cd137l) and/or cd40l |
US20200197517A1 (en) | 2018-12-18 | 2020-06-25 | Janssen Biotech, Inc. | Safe and Effective Method of Treating Lupus with Anti-IL12/IL23 Antibody |
BR112021013903A2 (en) | 2019-01-15 | 2021-09-21 | Janssen Biotech, Inc. | COMPOSITIONS AND METHODS OF ANTI-TNF ANTIBODIES FOR THE TREATMENT OF JUVENILE IDIOPATHIC ARTHRITIS |
WO2020152544A1 (en) | 2019-01-23 | 2020-07-30 | Janssen Biotech, Inc. | Anti-tnf antibody compositions for use in methods for the treatment of psoriatic arthritis |
EP3693063A1 (en) | 2019-02-06 | 2020-08-12 | Diaccurate | Methods and compositions for treating cancer |
JP2022525145A (en) | 2019-03-14 | 2022-05-11 | ヤンセン バイオテツク,インコーポレーテツド | A production method for producing an anti-IL12 / IL23 antibody composition. |
EP3938392A1 (en) | 2019-03-14 | 2022-01-19 | Janssen Biotech, Inc. | Methods for producing anti-tnf antibody compositions |
EP3938391A1 (en) | 2019-03-14 | 2022-01-19 | Janssen Biotech, Inc. | Methods for producing anti-tnf antibody compositions |
CN113840838A (en) | 2019-03-14 | 2021-12-24 | 詹森生物科技公司 | Methods of manufacture of compositions for the production of anti-TNF antibodies |
KR20210141583A (en) | 2019-03-18 | 2021-11-23 | 얀센 바이오테크 인코포레이티드 | Methods of Treating Psoriasis in Children Using Anti-IL-12/IL-23 Antibodies |
TW202106876A (en) | 2019-04-19 | 2021-02-16 | 日商中外製藥股份有限公司 | Chimeric receptor recognizing modification site of antibody |
JP2022534020A (en) | 2019-05-23 | 2022-07-27 | ヤンセン バイオテツク,インコーポレーテツド | Methods of treating inflammatory bowel disease with combination therapy of antibodies against IL-23 and TNF-alpha |
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AU6235294A (en) * | 1993-02-02 | 1994-08-29 | Scripps Research Institute, The | Methods for producing polypeptide binding sites |
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