US3927193A - Localization of tumors by radiolabelled antibodies - Google Patents

Localization of tumors by radiolabelled antibodies Download PDF

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US3927193A
US3927193A US361718A US36171873A US3927193A US 3927193 A US3927193 A US 3927193A US 361718 A US361718 A US 361718A US 36171873 A US36171873 A US 36171873A US 3927193 A US3927193 A US 3927193A
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antibody
cea
radiolabelled
tumors
tumor
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Hans John Hansen
Frederick James Primus
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F Hoffmann La Roche AG
Hoffmann La Roche Inc
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    • 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
    • A61K51/1048—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 determinant being a carcino embryonic antigen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo

Definitions

  • CEA Carcinoembryonic antigen
  • carcinoembryonic antigen includes both a mixture of antigenic components with CEA activity or a single such component.
  • radiolabelled antibody specific to CEA is injected into the subject and during the following eight days the subject is scanned with a photoscanning device which locates the sites at which the radiolabelled antibody is complexed with CEA. It is at these sites where the tumors associated with CEA are located.
  • the radioisotope suitable for use in this invention is an atom which does not interfere with the acitivity of the antibody. is sufficiently stable to be detected after complexation with CEA. has a half-life of sufficient duration to enable detection within 8 days and is phar maceutically inert, i.e., non-toxic and without pharmacological effect, in the amounts used and has a sufficient gamma intensity to be detected readily by the photoscanning techniques presently in use, i.e., 100 to 500 Kev (thousand electron volts). [t has been found that while P or are suitable for use in localizing tumors, is preferred for use in humans because of its favorable halflife. As a practical matter, any radioisotope with a half-life up to about eight days and a gamma emission of 10 to 5000 Kev is suitable for use.
  • the antibody is radio-iodinated by the procedure of Greenwood, Hunter and Glover, Biochem J. 89 ll4-l23. (I963) as modified by McConahy and Dixon. Int. Arch. Allergy 29 l85-l89, 1966.
  • the reaction is effected, for example, by using a 100 a! reaction mixture containing 50 ul. of chloramine-T (sodium p-toluenesulfochloramine); 40 ul. of goat anti-CEA lmmunoglobulin G in a phosphate buffer of pH 7.5 (10 mg./ml.
  • the reaction takes place in about L5 minutes at room temperature and is stopped by the addition of sodium metabisulfite.
  • the radioiodinated product can be separated from the unreacted radioisotope by chromatography in a cross-linked dextran gel column. e.g.. Sephadex G-ZS or Sephadex G- l by eluting with Tris-NaCl or PBS.
  • the labelled antibody is stabilized by mixing with a carrier protein such as serum or aqueous human albumin.
  • the resulting product has a specific activity of 2 about 4 to 6 Ci/ ug. This specific activity can be modified by altering the reaction conditions.
  • the level of the specific activity to be used should be below that which would interfere with the immunological activity of the anti-CEA antibody. It has been found that about 4 to 50 uCi/ug. are suitable with 4 to 6 uCi/ g preferred.
  • the antibody utilized is important to the operability of the process since it must be CEA specific and must be amenable to radiolabelling with sufficient activity per unit weight to result in a readily demonstrable effeet.
  • the antibodies are made by immunizing the animals against purified CEA. such as the CEA produced by the process disclosed in US. Pat. No. 3,697,638, and after a suitable time interval obtaining serum from the animal.
  • the antibodies are isolated from the serum by column chromatography using, for example. Sephadex (1-200 (Pharmacia, Uppsala, Swe den) and diethylaminoethyl (DEAE) cellulose (Whatman DE 52, H. Reeve Angel lnc., Clifton, N.J.). The purity and specificity of the antibodies is checked by immunoelectrophoresis and immunodiffusion.
  • the radiolabelled antibody is administered to the subject parenterally, preferably l.V.. in an amount sufficient to provide radioactivity which can be readily detected. but not so much that the radioactivity is unsafe for the patient.
  • This is accomplished utilizing a parenteral formulation containing about 300 to I000 uCi per ml. Generally about I to 2 ml. are administered.
  • a suitable formulation for injection contains a phosphate buffer at pH 7.0 and a stabilizer for the radiolabelled antibody.
  • hamsters having such tumors implanted are simultaneously injected with an equal mixture of anti-CEA antibody labelled with iodine-I25 and normal non-specific immunoglobulin G labelled with iodine-l3].
  • an equal mixture of anti-CEA antibody labelled with iodine-I25 and normal non-specific immunoglobulin G labelled with iodine-l3 After a suitable time, generally from I to 8 days, the hamsters are sacrificed and various organs as well as blood are tested for radioactivity and the percent of injected dose found per gram of tissue is calcu lated for each isotope.
  • the paired-labelled antibody technique i.e., the paired-labelled antibody technique.
  • tumors are preferentially radiolabelled by the labelled CEA antibody whereas the non-specific antibody is distributed randomly. This is shown by the localization ratio.
  • EXAMPLE 1 Radioiodination of Antibodies to CEA a Two mCi of l in the form of Nal are mixed with 40 ul. of goat anti-CEA lgG (ll) mg./ml. of 0.05 M phosphate, pH 7.5). Fifty 1.1.1. of Chloramine-T (3 mg/ml. phosphate buffer) are added and the mixture allowed to react for [.5 minutes at room temperature. Fifty ,ul. of Na- S Q, (6 mg./ml. phosphate buffer) is added to stop the reaction. The unbound radioisotpe is separated by filtration over a 2.6 X 35 cm Sephadex G-lUU column employing Tris-NaCl as the eluting 3 buffer. The iodinated antibody is collected and stabilized in the carrier protein 5% aqueous human albumin (Albuspan Parke. Davis).
  • the specific activity of the product is 4-6 uCi/ug.
  • the specific activity of the product is 4-6 uCi/ug.
  • normal goat lgG is radioiodinated in the same manner using it in place of the anti-CEA lgG.
  • CEA isolated from liver metastasis originating as adenocarcinoma of the colon was purified by column chromatography as described in US. Pat. No. 3,697,638. Goat antiserum to the thus prepared CEA was prepared by the so. injection into 2 sites of 500 ugm. of CEA in 1 ml. phosphate-buffered saline (PBS) containing 1 mg. of methylated bovine serum albumin and an equal volume of complete Freunds adjuvant. CEA was injected every 2 weeks for a total of 5 injections. The animals were terminally bled days following the final injection.
  • PBS phosphate-buffered saline
  • Diaflo UM I00 ultrafilter (retains l00,000 MW or greater).
  • the concentrated material was dialyzed against 0.0l M phosphate buffer, pH 8.0, and applied to a 2.6 X 25 cm. diethylaminoethyl (DEAE)-cellulose column equilibrated with the same buffer.
  • the anti-CEA IgG appearing between 260 to 600 ml. of elution volume was pooled, dialyzed against distilled water, and lyophilized. Immunoelectrophoresis and immunodiffusion were performed to evaluate the purity of the anti-CEA IgG.
  • EXAMPLE 3 An injectable formulation was prepared containing 0.200 gms. of radiolabelled anti-CEA antibody with an activity of 400 uCi/ml. of a phosphate buffered saline solution at pH 7.0 containing, by weight, 0.5 to 2.5% hepatitis free-human albumin.
  • EXAMPLE 4 Demonstration of Localization of Tumors
  • GW-39 a C EA producing human Signet-ring cell carcinoma of the colon.
  • 2.5 mg. of cortisone acetate was given subcutaneously.
  • the resulting tumor-bearing hamsters were administered an intracardial injection of the radiolabelled antibody and normal lgG mixture 1-4 weeks after implantation of tumor.
  • the anti-CEA antibody and normal IgG were labelled with l and "l. respectively.
  • the radioactivities were mixed 1: l on an activity basis and sterilely filtered.
  • l0-l2 uCi of each were given in a final volume of 0.2-0.3 ml.
  • Animals were administered Lugols solution (a stable Kl-l aqueous solution) in their drinking water to block thyroid uptake.
  • Lugols solution a stable Kl-l aqueous solution
  • each animal was exsanguinated by cardiac puncture and various organs (liver, spleen, kidney, lung. stomach, muscle, tumor) were removed and radioactivity was determined in each organ as well as in 1 ml. of blood using a gamma scintillation counter.
  • the percent of injected dose found per gram of tissue was calculated for each radioisotope.
  • a localization ratio was derived using the formula:
  • Anti -CEA Antibody/Normal lgG recovered in tissue
  • Anti-CEA Antibody/Normal lgG injected The level of significance between tumors and reference tissues was calculated by the Students t-test.

Abstract

A method of utilizing radiolabelled antibodies to carcinoembryonic antigens for determining the site of tumors which produce or are associated with carcinoembryonic antigen is disclosed.

Description

United States Patent [1 1 Hansen et a].
In] 3,927,193 [4 1 Dec. 16, 1975 1 LOCALIZATION OF TUMORS BY RADIOLABELLED ANTIBODIES [75) Inventors: Hans John Hansen, Allendale;
- Frederick James Primus, Waldwick,
both of NJ. 73 Assignee: nofiiimn-La Roche Inc., Nutley,
[221 Filed: May 18, 1973 [21] Appl. No.: 361,718
[52] US. Cl 424/1; 250/303 [51] Int. CL. A6IK 43/00; GOIT 1/161 [58] Field of 424/1, 9, 12; 23/230 B;
[56] References Cited UNITED STATES PATENTS 3,663,684 5/1972 Freedman et al 424/1 3,697,638 10/1972 Hansen 424/1 3,718,737 2/1973 Penn 424/1 3,735,001 5/1973 McRae et a1. 424/1 3,812,245 5/1974 Dugan 424/1 OTHER PUBLICATIONS Nuclear Science Abstracts, Vol. 24, No. 23, Dec. 15, 1970, p. 4722, Item No. 48,360.
Nuclear Science Abstracts, Vol. 26, No. 22, Nov. 30, 1972, p. 5345, Item No. 55,505.
Chemical Abstracts, Vol. 77, No. 1, July 3, 1972, p. 342, Item No. 3636n.
Chemical Abstracts, Vol. 77, No. 23, Nov. 30, 1972, p. 274, Item No. 150403.
Chemical Abstracts, V01. 78, No. 5, Feb. 5, 1973, p. 338, Item No. 27647p.
Chemical Abstracts, Vol. 78, No. 15, Apr. 16, 1973, p. 330, Item No. 95838b.
Primary Examiner-Benjamin R. Padgett Assistant Examiner Christine M. Nucker Attorney, Agent, or Firm-Samuel L. Welt; Jon S. Saxe; Gerald S. Rosen 1 1 ABSTRACT A method of utilizing radiolabelled antibodies to carcinoembryonic antigens for determining the site of tumors which produce or are associated with carcinoembryonic antigen is disclosed.
3 Claims, No Drawings LOCALIZATION OF TUMORS BY RADIOLABELLED ANTIBODIES BACKGROUND Carcinoembryonic antigen (CEA) is a mixture of several components, at least two of which have antigenic activity which is associated with human carcinoma. Methods such as those described in US. Pat. Nos. 3,663,684 and 3,697,638 have been developed for detecting the presence of CEA circulating in human blood. These known processes, however, do not provide a means for pinpointing the location and the source of the CEA. There is thus a need for a diagnostic method which will be satisfactory for locating the site of the tumor which produces or is associated with CEA.
DESCRIPTION OF THE INVENTION We have discovered that when a measured amount of radiolabelled antibody specific to carcinoembryonic antigen is administered parenterally, preferably by intravenous injection, the location of carcinoma tumors which either produce or are associated with carcinoembryonic antigen can be determined. As used herein carcinoembryonic antigen (CEA) includes both a mixture of antigenic components with CEA activity or a single such component.
In order to localize the tumor, radiolabelled antibody specific to CEA is injected into the subject and during the following eight days the subject is scanned with a photoscanning device which locates the sites at which the radiolabelled antibody is complexed with CEA. It is at these sites where the tumors associated with CEA are located.
The radioisotope suitable for use in this invention is an atom which does not interfere with the acitivity of the antibody. is sufficiently stable to be detected after complexation with CEA. has a half-life of sufficient duration to enable detection within 8 days and is phar maceutically inert, i.e., non-toxic and without pharmacological effect, in the amounts used and has a sufficient gamma intensity to be detected readily by the photoscanning techniques presently in use, i.e., 100 to 500 Kev (thousand electron volts). [t has been found that while P or are suitable for use in localizing tumors, is preferred for use in humans because of its favorable halflife. As a practical matter, any radioisotope with a half-life up to about eight days and a gamma emission of 10 to 5000 Kev is suitable for use.
When radioactive iodine is used, the antibody is radio-iodinated by the procedure of Greenwood, Hunter and Glover, Biochem J. 89 ll4-l23. (I963) as modified by McConahy and Dixon. Int. Arch. Allergy 29 l85-l89, 1966. The reaction is effected, for example, by using a 100 a! reaction mixture containing 50 ul. of chloramine-T (sodium p-toluenesulfochloramine); 40 ul. of goat anti-CEA lmmunoglobulin G in a phosphate buffer of pH 7.5 (10 mg./ml. 0.05 M phosphate, pH 7.5) and 2 mCi of I or 1" in the form of Nal. The reaction takes place in about L5 minutes at room temperature and is stopped by the addition of sodium metabisulfite. The radioiodinated product can be separated from the unreacted radioisotope by chromatography in a cross-linked dextran gel column. e.g.. Sephadex G-ZS or Sephadex G- l by eluting with Tris-NaCl or PBS. The labelled antibody is stabilized by mixing with a carrier protein such as serum or aqueous human albumin. The resulting product has a specific activity of 2 about 4 to 6 Ci/ ug. This specific activity can be modified by altering the reaction conditions. The level of the specific activity to be used should be below that which would interfere with the immunological activity of the anti-CEA antibody. It has been found that about 4 to 50 uCi/ug. are suitable with 4 to 6 uCi/ g preferred.
The antibody utilized is important to the operability of the process since it must be CEA specific and must be amenable to radiolabelling with sufficient activity per unit weight to result in a readily demonstrable effeet.
It has been found that animal sources used for producing the antibodies vary greatly from species to species and between animals within a species in their ability to produce large concentrations of highly specific CEA antibodies per unit volume of serum. It has been found that rabbits and goats are suitable. with goats preferred. The antibodies are made by immunizing the animals against purified CEA. such as the CEA produced by the process disclosed in US. Pat. No. 3,697,638, and after a suitable time interval obtaining serum from the animal. The antibodies are isolated from the serum by column chromatography using, for example. Sephadex (1-200 (Pharmacia, Uppsala, Swe den) and diethylaminoethyl (DEAE) cellulose (Whatman DE 52, H. Reeve Angel lnc., Clifton, N.J.). The purity and specificity of the antibodies is checked by immunoelectrophoresis and immunodiffusion.
The radiolabelled antibody is administered to the subject parenterally, preferably l.V.. in an amount sufficient to provide radioactivity which can be readily detected. but not so much that the radioactivity is unsafe for the patient. This is accomplished utilizing a parenteral formulation containing about 300 to I000 uCi per ml. Generally about I to 2 ml. are administered. A suitable formulation for injection contains a phosphate buffer at pH 7.0 and a stabilizer for the radiolabelled antibody.
In order to demonstrate that the radiolabelled antibody does localize tumors which produce or are associated with CEA, hamsters having such tumors implanted are simultaneously injected with an equal mixture of anti-CEA antibody labelled with iodine-I25 and normal non-specific immunoglobulin G labelled with iodine-l3]. After a suitable time, generally from I to 8 days, the hamsters are sacrificed and various organs as well as blood are tested for radioactivity and the percent of injected dose found per gram of tissue is calcu lated for each isotope. By means of this technique, i.e., the paired-labelled antibody technique. there is demonstrated that tumors are preferentially radiolabelled by the labelled CEA antibody whereas the non-specific antibody is distributed randomly. This is shown by the localization ratio.
The following examples illustrate the invention.
EXAMPLE 1 Radioiodination of Antibodies to CEA a. Two mCi of l in the form of Nal are mixed with 40 ul. of goat anti-CEA lgG (ll) mg./ml. of 0.05 M phosphate, pH 7.5). Fifty 1.1.1. of Chloramine-T (3 mg/ml. phosphate buffer) are added and the mixture allowed to react for [.5 minutes at room temperature. Fifty ,ul. of Na- S Q, (6 mg./ml. phosphate buffer) is added to stop the reaction. The unbound radioisotpe is separated by filtration over a 2.6 X 35 cm Sephadex G-lUU column employing Tris-NaCl as the eluting 3 buffer. The iodinated antibody is collected and stabilized in the carrier protein 5% aqueous human albumin (Albuspan Parke. Davis).
The specific activity of the product is 4-6 uCi/ug.
b. Two mCi of l in the form of Nal are mixed with 40 ul. of goat anti-CEA lgG l mg./ml. 0.05 M phosphate, pH 7.5). Fifty pl. of Chloramine-T (3 mg./ml. phosphate buffer) are added and the mixture allowed to react for L minutes at room temperature. The unbound radioisotope is separated by filtration over a 2.6 X 35 cm. Sephadex G- l00 column employing Tris- NaCl as the eluting buffer. The iodinated antibody is collected and stabilized in the carrier protein 5% aqueous human albumin (Albuspan Parke, Davis).
The specific activity of the product is 4-6 uCi/ug. For use in the paired labelled antibody technique normal goat lgG is radioiodinated in the same manner using it in place of the anti-CEA lgG.
EXAMPLE 2 CEA isolated from liver metastasis originating as adenocarcinoma of the colon was purified by column chromatography as described in US. Pat. No. 3,697,638. Goat antiserum to the thus prepared CEA was prepared by the so. injection into 2 sites of 500 ugm. of CEA in 1 ml. phosphate-buffered saline (PBS) containing 1 mg. of methylated bovine serum albumin and an equal volume of complete Freunds adjuvant. CEA was injected every 2 weeks for a total of 5 injections. The animals were terminally bled days following the final injection.
Twenty ml. of the resulting goat anti-CEA antiserum is dialyzed against 0.1 M Tris-HCl, pH 7.0, containing 0.15 M NaCl and 0.02% sodium azide and applied to a 5 X 90 cm cross-linked dextran gel column (Sephadex (3-200) equilibrated with the same buffer and maintained at 4C. Isolated fractions are tested for anti-CEA activity by the radioimmunoassay of Hansen (US. Pat. No. 3,697,638) and the material eluting between 690 and 930 ml. of' elution volume is pooled and concentrated by pressure filtration over a Diaflo UM I00 ultrafilter (retains l00,000 MW or greater). The concentrated material was dialyzed against 0.0l M phosphate buffer, pH 8.0, and applied to a 2.6 X 25 cm. diethylaminoethyl (DEAE)-cellulose column equilibrated with the same buffer. Following elution with l liter of starting buffer. the anti-CEA IgG appearing between 260 to 600 ml. of elution volume was pooled, dialyzed against distilled water, and lyophilized. Immunoelectrophoresis and immunodiffusion were performed to evaluate the purity of the anti-CEA IgG.
EXAMPLE 3 An injectable formulation was prepared containing 0.200 gms. of radiolabelled anti-CEA antibody with an activity of 400 uCi/ml. of a phosphate buffered saline solution at pH 7.0 containing, by weight, 0.5 to 2.5% hepatitis free-human albumin.
EXAMPLE 4 Demonstration of Localization of Tumors Male Syrian hamsters weighing 50-60 gms., were heterografted intramuscularly with a C EA producing human Signet-ring cell carcinoma of the colon. designated in the laboratory as GW-39. At the time of transplantation, 2.5 mg. of cortisone acetate was given subcutaneously. The resulting tumor-bearing hamsters were administered an intracardial injection of the radiolabelled antibody and normal lgG mixture 1-4 weeks after implantation of tumor. The anti-CEA antibody and normal IgG were labelled with l and "l. respectively. The radioactivities were mixed 1: l on an activity basis and sterilely filtered. l0-l2 uCi of each were given in a final volume of 0.2-0.3 ml. Animals were administered Lugols solution (a stable Kl-l aqueous solution) in their drinking water to block thyroid uptake. At timed intervals, each animal was exsanguinated by cardiac puncture and various organs (liver, spleen, kidney, lung. stomach, muscle, tumor) were removed and radioactivity was determined in each organ as well as in 1 ml. of blood using a gamma scintillation counter. Using appropriately diluted injection mixture standards, the percent of injected dose found per gram of tissue was calculated for each radioisotope. In addition, a localization ratio was derived using the formula:
Anti -CEA Antibody/Normal lgG recovered in tissue Anti-CEA Antibody/Normal lgG injected The level of significance between tumors and reference tissues was calculated by the Students t-test.
The results showing the tumor localization ratio at different time intervals after injection as set forth in the following Table:
TABLE I Localization Ratio Obtained in Tumor Following Injection of Anti-CEA Normal lgG Mixture Tumor 1 Standard Tumor Day After Localization Error Wt. Gms. Injection Ratio (S.E.] S.E.
l l.6l5l .0355 0.49 t 0.33 2 l.9607 .0826 0.58 t 0.32 4 2.4825 .l289 0.94 i 0.46 6 3.5392 .2l56 l.2 0.72 8 4.l434 .6506 2.23 1 l 2 Table 2 Tumor/Blood Ratios Obtained After Injection of I' Labelled Anti-CEA Antibody and l Labelled Normal Antibody Antibody Anti-CEA Antibody Normal Antibody Days After Tumor/Blood Tumor/Blood Injection Ratio Ratio l .8l32 .4866 2 .9960 .5330 4 l.l420 .5080 6 l.75l6 .5800 8 2.3016 .5350
We claim:
I. A method for determining the location of a tumor which either produces or is associated with carcinoem- 6 resulting uptake of radiolabelled antibody by said tumor.
2. The method of claim 1 wherein the antibody is radiolabelled with iodinel 3 l.
3. The method of claim I wherein the subject is injected intravenously.

Claims (3)

1. A METHOD FOR DETERMINING THE LOCATION OF A TUMOR WHICH EITHER PRODUCES OR IS ASSOCIATED WITH CARCINOEMBRYONIC ANTIGEN WHICH COMPRISES INJECTING A SUBJECT PARENTERALLY WITH AN ANTIBODY RADIO LABELLED WITH A PHARMOCOLOGICALLY INERT RADIOISOTOPE HAVING A HALF-LIFE UP TO ABOUT 8 DAYS AND A GAMMA EMISSION OF 10 TO 5000 KEV SAID ANTIBODY BEING SPECIFIC TO CARCINOEMBRYONIC ANTIGEN AND SUBSEQUENTLY SCANNING THE SUBJECT WITH A PHOTOSCANNING DEVICE TO DETERMINE THE LOCATION OF THE RESULTING UPTAKE OF RADIOLABELLED ANTIBODY BY SAID TUMOR.
2. The method of claim 1 wherein the antibody is radiolabellEd with iodine-131.
3. The method of claim 1 wherein the subject is injected intravenously.
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Cited By (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4132769A (en) * 1974-10-30 1979-01-02 Osther Kurt B Cancer antigen, cancer therapy, and cancer diagnosis
US4152410A (en) * 1975-09-03 1979-05-01 Eisai Co., Ltd. Diagnosis reagent for neoplasm and method for diagnosis of neoplasm
DE2828941A1 (en) * 1978-06-30 1980-01-10 Robert Thomas Gordon CANCER TREATMENT AGENTS
EP0035265A2 (en) * 1980-03-03 1981-09-09 Milton David Goldenberg Agent for tumor localization and therapy with labeled antibodies and antibody fragments
US4303636A (en) * 1974-08-20 1981-12-01 Gordon Robert T Cancer treatment
US4323546A (en) * 1978-05-22 1982-04-06 Nuc Med Inc. Method and composition for cancer detection in humans
US4331647A (en) * 1980-03-03 1982-05-25 Goldenberg Milton David Tumor localization and therapy with labeled antibody fragments specific to tumor-associated markers
US4348376A (en) * 1980-03-03 1982-09-07 Goldenberg Milton David Tumor localization and therapy with labeled anti-CEA antibody
US4361544A (en) * 1980-03-03 1982-11-30 Goldenberg Milton David Tumor localization and therapy with labeled antibodies specific to intracellular tumor-associated markers
EP0090025A1 (en) * 1981-09-28 1983-10-05 Roberto Luis Dr. Ceriani Specific mammary gland labelling
US4444744A (en) * 1980-03-03 1984-04-24 Goldenberg Milton David Tumor localization and therapy with labeled antibodies to cell surface antigens
US4460561A (en) * 1980-03-03 1984-07-17 Goldenberg M David Tumor localization and therapy with labeled antibodies specific to intracellular tumor-associated markers
US4618577A (en) * 1983-02-09 1986-10-21 The Regents Of The University Of California Human-human hybridoma, CLNH5
USRE32417E (en) * 1979-10-29 1987-05-12 Summa Medical Corporation Radiolabeled antibody to anti-tumor associated antigen and process
US4837003A (en) * 1984-09-13 1989-06-06 Mallinckrodt, Inc. Radiolabeled antibody fragments
WO1989012465A1 (en) * 1988-06-13 1989-12-28 Schering Aktiengesellschaft A method for the visual display of tumors using monoclonal antibodies
US5130116A (en) * 1988-10-12 1992-07-14 Centocor, Inc. Radiotherapeutic immunoconjugates labeled with iodine-125
WO1993019668A1 (en) * 1992-04-07 1993-10-14 Immunomedics, Inc. Method and kit for imaging and treating organs and tissues
US5256395A (en) * 1986-09-19 1993-10-26 Immunotech Partners Affinity enhancement immunological reagents for in vivo detection and killing of specific target cells
US5273743A (en) * 1990-03-09 1993-12-28 Hybritech Incorporated Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent
US5364613A (en) * 1989-04-07 1994-11-15 Sieving Paul F Polychelants containing macrocyclic chelant moieties
WO1996039937A1 (en) * 1995-06-07 1996-12-19 The Regents Of The University Of California Microfabricated devices for diagnostic applications
US5670132A (en) * 1994-09-20 1997-09-23 Immunomedics, Inc. Modified radioantibody fragments for reduced renal uptake
US6013772A (en) * 1986-08-13 2000-01-11 Bayer Corporation Antibody preparations specifically binding to unique determinants of CEA antigens or fragments thereof and use of the antibody preparations in immunoassays
US6051693A (en) * 1982-05-21 2000-04-18 The Regents Of The University Of California CLNH11-specific antibodies
US6274118B1 (en) 1993-07-14 2001-08-14 Nordion International Inc. Localization and therapy of non-prostatic endocrine cancer with agents directed against prostate specific antigen
US20010018186A1 (en) * 1996-03-21 2001-08-30 Hirth Klaus Peter Method for molecular diagnosis of tumor angiogenesis and metastasis
US6361774B1 (en) 1999-09-17 2002-03-26 Immunomedics, Inc. Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug
US6458933B1 (en) 1998-05-20 2002-10-01 Immunomedics, Inc. Therapeutic using a bispecific antibody
US20020165149A1 (en) * 2000-12-08 2002-11-07 Kranz David M. Mutated class II major histocompatibility proteins
US20030003102A1 (en) * 2001-03-30 2003-01-02 University Of Massachusetts Morpholino imaging and therapy
US20030003051A1 (en) * 2001-06-11 2003-01-02 Inverardi Luca A. Methods of achieving transplantation tolerance through radioablation of hemolymphopoietic cell populations
WO2003074569A2 (en) 2002-03-01 2003-09-12 Immunomedics, Inc. Bispecific antibody point mutations for enhancing rate of clearance
US20030232011A1 (en) * 1996-05-03 2003-12-18 Immunomedics, Inc. Targeted combination immunotherapy
US6759243B2 (en) 1998-01-20 2004-07-06 Board Of Trustees Of The University Of Illinois High affinity TCR proteins and methods
WO2004074434A2 (en) 2003-01-31 2004-09-02 Immunomedics, Inc. Methods and compositions for administering therapeutic and diagnostic agents
US20050136001A1 (en) * 2003-07-29 2005-06-23 Immunomedics, Inc. Fluorinated carbohydrate conjugates
US20050260131A1 (en) * 2004-05-20 2005-11-24 General Electric Company Pharmaceuticals for enhanced delivery to disease targets
US20060104949A1 (en) * 2001-12-05 2006-05-18 Popplewell Andrew G Expression Control Using Variable Intergenic Sequences
US7053210B2 (en) 2002-07-02 2006-05-30 Health Research, Inc. Efficient synthesis of pyropheophorbide a and its derivatives
US20080031813A1 (en) * 1996-05-03 2008-02-07 Griffiths Gary L Targeted Combination Immunotherapy of Cancer and Infectious Diseases
US7501509B2 (en) 2002-06-27 2009-03-10 Health Research, Inc. Water soluble tetrapyrollic photosensitizers for photodynamic therapy
EP2042869A2 (en) 1999-12-06 2009-04-01 Board Of Trustees Of The University Of Illinois High affinity TCR proteins and methods
WO2009100194A2 (en) 2008-02-06 2009-08-13 Immunomedics, Inc. Camptothecin-binding moiety conjugates
US7897140B2 (en) 1999-12-23 2011-03-01 Health Research, Inc. Multi DTPA conjugated tetrapyrollic compounds for phototherapeutic contrast agents
WO2011044186A1 (en) 2009-10-06 2011-04-14 The Board Of Trustees Of The University Of Illinois Human single-chain t cell receptors
EP2418223A2 (en) 2006-06-12 2012-02-15 Emergent Product Development Seattle, LLC Single-chain multivalent binding proteins with effector function
WO2014092804A1 (en) 2012-12-13 2014-06-19 Immunomedics, Inc. Dosages of immunoconjugates of antibodies and sn-38 for improved efficacy and decreased toxicity
US8853366B2 (en) 2001-01-17 2014-10-07 Emergent Product Development Seattle, Llc Binding domain-immunoglobulin fusion proteins
WO2015026845A2 (en) 2013-08-19 2015-02-26 Abbott Molecular Inc. Nucleotide analogs
WO2015077607A1 (en) 2013-11-22 2015-05-28 The Board Of Trustees Of The University Of Illinois Engineered high-affinity human t cell receptors
US9101609B2 (en) 2008-04-11 2015-08-11 Emergent Product Development Seattle, Llc CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof
WO2017004144A1 (en) 2015-07-01 2017-01-05 Immunomedics, Inc. Antibody-sn-38 immunoconjugates with a cl2a linker
EP3243527A1 (en) 2009-02-13 2017-11-15 Immunomedics, Inc. Immunoconjugates with an intracellularly-cleavable linkage
EP3263598A1 (en) 2006-03-23 2018-01-03 Immunomedics Inc. Camptothecin-binding moiety conjugates
US9931412B2 (en) 2013-02-08 2018-04-03 The Regents Of The University Of Michigan Targeted theranostics
US10143748B2 (en) 2005-07-25 2018-12-04 Aptevo Research And Development Llc B-cell reduction using CD37-specific and CD20-specific binding molecules
WO2019046556A1 (en) 2017-09-01 2019-03-07 East Carolina University Compounds, compositions, kits, and methods for activating immune cells and/or an immune system response
EP3586874A1 (en) 2012-08-14 2020-01-01 IBC Pharmaceuticals, Inc. T-cell redirecting bispecific antibodies for treatment of disease
EP3636664A1 (en) 2012-07-27 2020-04-15 The Board of Trustees of the University of Illinois Engineering t-cell receptors
US10836774B2 (en) 2016-11-30 2020-11-17 North Carolina State University Methods for making bacteriochlorin macrocycles comprising an annulated isocyclic ring and related compounds
WO2020236818A1 (en) 2019-05-20 2020-11-26 Nirvana Sciences Inc. Narrow emission dyes, compositions comprising same, and methods for making and using same
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3663684A (en) * 1970-06-01 1972-05-16 Hoffmann La Roche Carcinoembryonic antigen and diagnostic method using radioactive iodine
US3697638A (en) * 1970-06-01 1972-10-10 Hoffmann La Roche Antigens
US3718737A (en) * 1967-10-20 1973-02-27 H Penn Process of treating bile and novel iodine-131 complex
US3735001A (en) * 1972-05-24 1973-05-22 Atomic Energy Commission Technetium bone scanning medium
US3812245A (en) * 1972-08-21 1974-05-21 Research Corp Novel compositions for radiotracer localization of deep vein thrombi

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3718737A (en) * 1967-10-20 1973-02-27 H Penn Process of treating bile and novel iodine-131 complex
US3663684A (en) * 1970-06-01 1972-05-16 Hoffmann La Roche Carcinoembryonic antigen and diagnostic method using radioactive iodine
US3697638A (en) * 1970-06-01 1972-10-10 Hoffmann La Roche Antigens
US3735001A (en) * 1972-05-24 1973-05-22 Atomic Energy Commission Technetium bone scanning medium
US3812245A (en) * 1972-08-21 1974-05-21 Research Corp Novel compositions for radiotracer localization of deep vein thrombi

Cited By (111)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4303636A (en) * 1974-08-20 1981-12-01 Gordon Robert T Cancer treatment
US4132769A (en) * 1974-10-30 1979-01-02 Osther Kurt B Cancer antigen, cancer therapy, and cancer diagnosis
US4152410A (en) * 1975-09-03 1979-05-01 Eisai Co., Ltd. Diagnosis reagent for neoplasm and method for diagnosis of neoplasm
US4323546A (en) * 1978-05-22 1982-04-06 Nuc Med Inc. Method and composition for cancer detection in humans
DE2828941A1 (en) * 1978-06-30 1980-01-10 Robert Thomas Gordon CANCER TREATMENT AGENTS
USRE32417E (en) * 1979-10-29 1987-05-12 Summa Medical Corporation Radiolabeled antibody to anti-tumor associated antigen and process
US4348376A (en) * 1980-03-03 1982-09-07 Goldenberg Milton David Tumor localization and therapy with labeled anti-CEA antibody
US4460561A (en) * 1980-03-03 1984-07-17 Goldenberg M David Tumor localization and therapy with labeled antibodies specific to intracellular tumor-associated markers
EP0035265A3 (en) * 1980-03-03 1982-04-07 Milton David Goldenberg Tumor localization and therapy with labeled antibodies and antibody fragments specific to tumor-associated markers
US4331647A (en) * 1980-03-03 1982-05-25 Goldenberg Milton David Tumor localization and therapy with labeled antibody fragments specific to tumor-associated markers
WO1981002522A1 (en) * 1980-03-03 1981-09-17 M Goldenberg Tumor localization and therapy with labeled antibodies and antibody fragments specific to tumor-associated markers
US4361544A (en) * 1980-03-03 1982-11-30 Goldenberg Milton David Tumor localization and therapy with labeled antibodies specific to intracellular tumor-associated markers
EP0035265A2 (en) * 1980-03-03 1981-09-09 Milton David Goldenberg Agent for tumor localization and therapy with labeled antibodies and antibody fragments
JPS57500195A (en) * 1980-03-03 1982-02-04
US4444744A (en) * 1980-03-03 1984-04-24 Goldenberg Milton David Tumor localization and therapy with labeled antibodies to cell surface antigens
EP0090025A4 (en) * 1981-09-28 1984-01-12 Roberto Luis Ceriani Specific mammary gland labelling.
EP0090025A1 (en) * 1981-09-28 1983-10-05 Roberto Luis Dr. Ceriani Specific mammary gland labelling
US6051229A (en) * 1982-05-21 2000-04-18 The Regents Of The University Of California Human-human hybridom for neoplasms CLNH5 and CLNH11 specific antibody compositions
US6051387A (en) * 1982-05-21 2000-04-18 The Regents Of The University Of California Methods of determining the presence of a neoplasm with CLNH5- and CLNH11-specific antibodies
US6051693A (en) * 1982-05-21 2000-04-18 The Regents Of The University Of California CLNH11-specific antibodies
US4618577A (en) * 1983-02-09 1986-10-21 The Regents Of The University Of California Human-human hybridoma, CLNH5
US4837003A (en) * 1984-09-13 1989-06-06 Mallinckrodt, Inc. Radiolabeled antibody fragments
US5776093A (en) * 1985-07-05 1998-07-07 Immunomedics, Inc. Method for imaging and treating organs and tissues
US5697902A (en) * 1985-07-05 1997-12-16 Immunomedics, Inc. Method for imaging and treating organs and tissues
US5776095A (en) * 1985-07-05 1998-07-07 Immunomedics, Inc. Method and kit for imaging and treating organs and tissues
US5776094A (en) * 1985-07-05 1998-07-07 Immunomedics, Inc. Method and kit for imaging and treating organs and tissues
US6013772A (en) * 1986-08-13 2000-01-11 Bayer Corporation Antibody preparations specifically binding to unique determinants of CEA antigens or fragments thereof and use of the antibody preparations in immunoassays
US6022958A (en) * 1986-08-13 2000-02-08 Bayer Corporation cDNAs coding for members of the carcinoembryonic antigen family
US5256395A (en) * 1986-09-19 1993-10-26 Immunotech Partners Affinity enhancement immunological reagents for in vivo detection and killing of specific target cells
WO1989012465A1 (en) * 1988-06-13 1989-12-28 Schering Aktiengesellschaft A method for the visual display of tumors using monoclonal antibodies
US5130116A (en) * 1988-10-12 1992-07-14 Centocor, Inc. Radiotherapeutic immunoconjugates labeled with iodine-125
US5364613A (en) * 1989-04-07 1994-11-15 Sieving Paul F Polychelants containing macrocyclic chelant moieties
US5273743A (en) * 1990-03-09 1993-12-28 Hybritech Incorporated Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent
WO1993019668A1 (en) * 1992-04-07 1993-10-14 Immunomedics, Inc. Method and kit for imaging and treating organs and tissues
US20110117105A1 (en) * 1992-04-07 2011-05-19 Immunomedics, Inc. Method of treating immune disease using b-cell antibodies
US7811570B2 (en) 1992-04-07 2010-10-12 Immunomedics, Inc. Method of affecting a function of or ablating a non-malignant cell
US20060067885A1 (en) * 1992-04-07 2006-03-30 Immunomedics, Inc. Method and kit for imaging and treating organs and tissues
US6274118B1 (en) 1993-07-14 2001-08-14 Nordion International Inc. Localization and therapy of non-prostatic endocrine cancer with agents directed against prostate specific antigen
US5670132A (en) * 1994-09-20 1997-09-23 Immunomedics, Inc. Modified radioantibody fragments for reduced renal uptake
WO1996039937A1 (en) * 1995-06-07 1996-12-19 The Regents Of The University Of California Microfabricated devices for diagnostic applications
US20010018186A1 (en) * 1996-03-21 2001-08-30 Hirth Klaus Peter Method for molecular diagnosis of tumor angiogenesis and metastasis
US7011812B1 (en) 1996-05-03 2006-03-14 Immunomedics, Inc. Targeted combination immunotherapy of cancer and infectious diseases
US20060002855A1 (en) * 1996-05-03 2006-01-05 Immunomedics, Inc. Targeted combination immunotherapy of cancer and infectious diseases
US7514066B2 (en) 1996-05-03 2009-04-07 Immunomedics, Inc. Targeted combination immunotherapy of cancer and infectious diseases
US20080031813A1 (en) * 1996-05-03 2008-02-07 Griffiths Gary L Targeted Combination Immunotherapy of Cancer and Infectious Diseases
US7931890B2 (en) 1996-05-03 2011-04-26 Immunomedics, Inc. Targeted combination immunotherapy of cancer and infectious diseases
US20030232011A1 (en) * 1996-05-03 2003-12-18 Immunomedics, Inc. Targeted combination immunotherapy
US7300644B2 (en) 1996-05-03 2007-11-27 Immunomedics, Inc. Targeted combination immunotherapy
US6759243B2 (en) 1998-01-20 2004-07-06 Board Of Trustees Of The University Of Illinois High affinity TCR proteins and methods
US7569357B2 (en) 1998-01-20 2009-08-04 Board Of Trustees Of The University Of Illinois High affinity TCR proteins and methods
US7230084B2 (en) 1998-05-20 2007-06-12 Immunomedics, Inc. Therapeutic using a bispecific antibody
US8466261B2 (en) 1998-05-20 2013-06-18 Immunomedics, Inc. Therapeutic using a bispecific antibody
US20030103982A1 (en) * 1998-05-20 2003-06-05 Immunomedics, Inc. Therapeutic using a bispecific antibody
US6458933B1 (en) 1998-05-20 2002-10-01 Immunomedics, Inc. Therapeutic using a bispecific antibody
US7470429B2 (en) 1998-09-18 2008-12-30 Immunomedics, Inc. Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug
US20020114808A1 (en) * 1998-09-18 2002-08-22 Immunomedics, Inc. Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug
US6361774B1 (en) 1999-09-17 2002-03-26 Immunomedics, Inc. Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug
EP2042869A2 (en) 1999-12-06 2009-04-01 Board Of Trustees Of The University Of Illinois High affinity TCR proteins and methods
EP2287185A2 (en) 1999-12-06 2011-02-23 Board Of Trustees Of The University Of Illinois High affinity TCR proteins and methods
EP2336775A2 (en) 1999-12-06 2011-06-22 Board Of Trustees Of The University Of Illinois High affinity TCR proteins and methods
US7897140B2 (en) 1999-12-23 2011-03-01 Health Research, Inc. Multi DTPA conjugated tetrapyrollic compounds for phototherapeutic contrast agents
US20020165149A1 (en) * 2000-12-08 2002-11-07 Kranz David M. Mutated class II major histocompatibility proteins
US8853366B2 (en) 2001-01-17 2014-10-07 Emergent Product Development Seattle, Llc Binding domain-immunoglobulin fusion proteins
US6899864B2 (en) 2001-03-30 2005-05-31 Immunomedics, Inc. Morpholino imaging and therapy
US20030003102A1 (en) * 2001-03-30 2003-01-02 University Of Massachusetts Morpholino imaging and therapy
US20030003051A1 (en) * 2001-06-11 2003-01-02 Inverardi Luca A. Methods of achieving transplantation tolerance through radioablation of hemolymphopoietic cell populations
US7419659B2 (en) 2001-12-05 2008-09-02 Ucb Pharma S.A. Expression control using variable intergenic sequences
US20060104949A1 (en) * 2001-12-05 2006-05-18 Popplewell Andrew G Expression Control Using Variable Intergenic Sequences
WO2003074569A2 (en) 2002-03-01 2003-09-12 Immunomedics, Inc. Bispecific antibody point mutations for enhancing rate of clearance
US7501509B2 (en) 2002-06-27 2009-03-10 Health Research, Inc. Water soluble tetrapyrollic photosensitizers for photodynamic therapy
USRE43274E1 (en) 2002-06-27 2012-03-27 Health Research, Inc. Fluorinated photosensitizers related to chlorins and bacteriochlorins for photodynamic therapy
US7820143B2 (en) 2002-06-27 2010-10-26 Health Research, Inc. Water soluble tetrapyrollic photosensitizers for photodynamic therapy
US7053210B2 (en) 2002-07-02 2006-05-30 Health Research, Inc. Efficient synthesis of pyropheophorbide a and its derivatives
WO2004074434A2 (en) 2003-01-31 2004-09-02 Immunomedics, Inc. Methods and compositions for administering therapeutic and diagnostic agents
US8038983B2 (en) 2003-07-29 2011-10-18 Immunomedics, Inc. Fluorinated carbohydrate conjugates
US20050136001A1 (en) * 2003-07-29 2005-06-23 Immunomedics, Inc. Fluorinated carbohydrate conjugates
US20050260131A1 (en) * 2004-05-20 2005-11-24 General Electric Company Pharmaceuticals for enhanced delivery to disease targets
US10307481B2 (en) 2005-07-25 2019-06-04 Aptevo Research And Development Llc CD37 immunotherapeutics and uses thereof
US10143748B2 (en) 2005-07-25 2018-12-04 Aptevo Research And Development Llc B-cell reduction using CD37-specific and CD20-specific binding molecules
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US8409577B2 (en) 2006-06-12 2013-04-02 Emergent Product Development Seattle, Llc Single chain multivalent binding proteins with effector function
WO2009100194A2 (en) 2008-02-06 2009-08-13 Immunomedics, Inc. Camptothecin-binding moiety conjugates
US9101609B2 (en) 2008-04-11 2015-08-11 Emergent Product Development Seattle, Llc CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof
EP3939617A1 (en) 2009-02-13 2022-01-19 Immunomedics, Inc. Conjugates with an intracellularly-cleavable linkage
EP3912643A1 (en) 2009-02-13 2021-11-24 Immunomedics Inc. Immunoconjugates with an intracellularly-cleavable linkage
EP3903829A1 (en) 2009-02-13 2021-11-03 Immunomedics Inc. Immunoconjugates with an intracellularly-cleavable linkage
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EP3470087A1 (en) 2009-02-13 2019-04-17 Immunomedics, Inc. Lyophilised compositions of immunoconjugates with an intracellularly-cleavable linkage
WO2011044186A1 (en) 2009-10-06 2011-04-14 The Board Of Trustees Of The University Of Illinois Human single-chain t cell receptors
US10464987B2 (en) 2009-10-06 2019-11-05 Abbvie Inc. Human single-chain T cell receptors
EP3636664A1 (en) 2012-07-27 2020-04-15 The Board of Trustees of the University of Illinois Engineering t-cell receptors
EP3586874A1 (en) 2012-08-14 2020-01-01 IBC Pharmaceuticals, Inc. T-cell redirecting bispecific antibodies for treatment of disease
WO2014092804A1 (en) 2012-12-13 2014-06-19 Immunomedics, Inc. Dosages of immunoconjugates of antibodies and sn-38 for improved efficacy and decreased toxicity
EP4035689A1 (en) 2012-12-13 2022-08-03 Immunomedics Inc. Dosages of immunoconjugates of antibodies and sn-38 for improved efficacy and decreased toxicity
US9931412B2 (en) 2013-02-08 2018-04-03 The Regents Of The University Of Michigan Targeted theranostics
WO2015026845A2 (en) 2013-08-19 2015-02-26 Abbott Molecular Inc. Nucleotide analogs
US10995363B2 (en) 2013-08-19 2021-05-04 Abbott Molecular Inc. Nucleotide analogs
US10577646B2 (en) 2013-08-19 2020-03-03 Abbott Molecular Inc. Nucleotide analogs
US9932623B2 (en) 2013-08-19 2018-04-03 Abbott Molecular Inc. Nucleotide analogs
WO2015077607A1 (en) 2013-11-22 2015-05-28 The Board Of Trustees Of The University Of Illinois Engineered high-affinity human t cell receptors
WO2017004144A1 (en) 2015-07-01 2017-01-05 Immunomedics, Inc. Antibody-sn-38 immunoconjugates with a cl2a linker
US11352426B2 (en) 2015-09-21 2022-06-07 Aptevo Research And Development Llc CD3 binding polypeptides
US10960013B2 (en) 2016-03-04 2021-03-30 East Carolina University J-series prostaglandin-ethanolamides as novel therapeutics for skin and/or oral disorders
US10919904B2 (en) 2016-08-17 2021-02-16 North Carolina State University Northern-southern route to synthesis of bacteriochlorins
US10836774B2 (en) 2016-11-30 2020-11-17 North Carolina State University Methods for making bacteriochlorin macrocycles comprising an annulated isocyclic ring and related compounds
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US11571401B2 (en) 2017-09-01 2023-02-07 East Carolina University Compounds, compositions, kits, and methods for activating immune cells and/or an immune system response
EP4265257A1 (en) 2017-09-01 2023-10-25 East Carolina University Combination of a j-series prostaglandin-ethanolamide and a checkpoint inhibitor for use in treating cancer
WO2020236818A1 (en) 2019-05-20 2020-11-26 Nirvana Sciences Inc. Narrow emission dyes, compositions comprising same, and methods for making and using same

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