NZ729451B2 - Antibodies, compositions, and uses - Google Patents
Antibodies, compositions, and uses Download PDFInfo
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- NZ729451B2 NZ729451B2 NZ729451A NZ72945115A NZ729451B2 NZ 729451 B2 NZ729451 B2 NZ 729451B2 NZ 729451 A NZ729451 A NZ 729451A NZ 72945115 A NZ72945115 A NZ 72945115A NZ 729451 B2 NZ729451 B2 NZ 729451B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
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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
- A61K51/1018—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 material from animals or humans
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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
- A61K51/1027—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 receptors, cell-surface antigens or cell-surface determinants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2299/00—Coordinates from 3D structures of peptides, e.g. proteins or enzymes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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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
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
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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
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- 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'
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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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
- C07K2317/567—Framework region [FR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
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- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
Abstract
The present disclosure describes anti-B7H3 antibody agents and uses relating thereto. Among other things, the present disclosure demonstrates particular immunomodulatory effectiveness of certain such antibodies. The present disclosure further describes particularly high-affinity or otherwise useful antibodies and antibody agents based thereon, including particularly certain humanized and/or affinity matured versions of an 8H9 antibody. In some embodiments, provided antibody agents are useful, for example, in the treatment of cancer. In some embodiments, provided antibody agents are useful in relieving immunosuppression, for example mediated by B7H3-positive cells.
Claims (26)
1. An antibody agent that binds specifically to protein 2Ig-B7H3 or 4Ig-B7H3, wherein the antibody agent comprises: 5 light chain CDR1, CDR2, and CDR3 as set forth in SEQ ID NOs: 34, 36, and 38, respectively, and heavy chain CDR1, CDR2, and CDR3 as set forth in SEQ ID NOs: 58, 60, and 62, tively.
2. The antibody agent of claim 1, comprising an immunoglobulin heavy chain and an 10 immunoglobulin light chain, wherein the antibody agent binds specifically to protein 2Ig-B7H3 or 4Ig-B7H3, and wherein said immunoglobulin light chain variable domain comprises a sequence as set forth in a SEQ ID NO. selected from the group consisting of SEQ ID NO.: 5, 7, and 8, and said globulin heavy chain variable domain comprises a sequence as set forth in a SEQ ID NO. selected from the group consisting of SEQ ID NO.: 13, 15, and 16.
3. The antibody agent of claim 2, wherein: (i) the immunoglobulin light chain is set forth in SEQ ID NO.: 5 and the globulin heavy chain is set forth in SEQ ID NO.: 13; (ii) the immunoglobulin light chain is set forth in SEQ ID NO.: 7 and the 20 immunoglobulin heavy chain is set forth in SEQ ID NO.: 15; or (iii) the immunoglobulin light chain is set forth in SEQ ID NO.: 8 and the immunoglobulin heavy chain is set forth in SEQ ID NO.: 16.
4. The antibody agent of claim 2, n the immunoglobulin light chain is set forth in 25 SEQ ID NO.: 5 and the immunoglobulin heavy chain is set forth in SEQ ID NO.: 13.
5. The antibody agent of claim 2, wherein the immunoglobulin light chain is set forth in
SEQ ID NO.: 7 and the immunoglobulin heavy chain is set forth in SEQ ID NO.: 15. 30 6. The antibody agent of claim 2, n the immunoglobulin light chain is fused to a polypeptide set forth in SEQ ID NO.: 30 or SEQ ID NO.: 31.
7. The antibody agent of claim 1 or claim 2, conjugated to a therapeutic agent or detection agent.
8. The antibody agent of claim 7, wherein the antibody is conjugated to a radio-isotope, a drug agent, a nanoparticle, or an immune-toxin.
9. The antibody agent of claim 7, wherein the antibody is conjugated to a diagnostic or 5 g agent, or both.
10. The antibody agent of claim 1 or claim 2, wherein the antibody agent is a bispecific antibody having a first and a second specificity, and wherein the first specificity binds to protein 2Ig-B7H3 or 4Ig-B7H3, and the second icity binds to CD3 on T cells or 1,4,7,10- 10 tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).
11. An scFv that binds specifically to protein 2Ig-B7H3 or 4Ig-B7H3 and ses the polypeptide set forth in a SEQ ID NO. selected from the group consisting of SEQ ID NO.: 24, 26 and 27.
12. The scFv of claim 11, wherein the polypeptide is fused to a second polypeptide set forth in SEQ ID NO.: 28 or SEQ ID NO.: 29.
13. The scFv of claim 11 or claim 12, wherein the scFv is conjugated to a therapeutic agent 20 or detection agent.
14. A pharmaceutical composition sing the antibody agent of any one of claims 1 to 10 or the scFv of any one of claims 11 to 13, and a pharmaceutically acceptable carrier. 25
15. Use of the antibody agent of any one of claims 1 to 10 or the scFv of any one of claims 11 to 13 in the manufacture of a ment for treating cancer in a t.
16. The use of claim 15, wherein the cancer is or comprises a neuroblastoma. 30
17. The use of claim 15, wherein the cancer is or comprises a cervical cancer.
18. The use of claim 15, wherein the cancer comprises B7H3-positive tumor cells.
19. Use of the antibody agent of any one of claims 1 to 10 or the scFv of any one of claims 35 11 to 13 in the manufacture of a medicament for ting the immune system in a patient.
20. Use of an antibody agent that binds to B7H3’s FG-loop in the manufacture of a medicament for enchancing T-cell mediated toxicity in a subject, wherein the antibody agent comprises: light chain CDR1, CDR2, and CDR3 as set forth in SEQ ID NOs: 34, 36, and 38, 5 respectively, and heavy chain CDR1, CDR2, and CDR3 as set forth in SEQ ID NOs: 58, 60, and 62, respectively.
21. The use of claim 20, wherein the antibody agent comprises an immunoglobulin heavy chain and an immunoglobulin light chain, wherein said globulin heavy chain comprises 10 a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 15, and said immunoglobulin light chain comprises a ce as set forth in SEQ ID NO: 5 or SEQ ID NO: 7.
22. A DNA or RNA encoding an antibody agent of any one of claims 1 to 10. 15
23. An isolated cell that expresses an antibody agent of any one of claims 1 to 10.
24. A method of preparing an isolated cell that ses an antibody agent, comprising transfecting or virally transducing a cell with the DNA of claim 22. 20
25. Use of the antibody agent of any one of claims 1 to 10 in the manufacture of a medicament for treating a patient by tmental radioimmunotherapy (cRIT).
26. The use of claim 25, wherein the medicament is to be administered intrathecally, intraperitoneally, or by convection enhanced delivery. SUBSTITUTE SHEET (RULE 26) HUMANIZATION BASED ON CDRGRAFTING AND U HOMOLOGYTO HUMAN TEMPLATES ch8H9AND hU8H9 H1L1, H1L2, H2L1, H2L2 IN SILICO SIMULATIONS OF 8H9 HOMOLOGY 3 MODEL STRUCTURE, TO R AFFINITY hu8H9 Q 3,1 IN SILICO SIMULATION YEAST DISPLAYAFFINITY MANUTRATION, 0F 8H9 CRYSTAL U TO ENHANCE ANTIGEN BINDING STRUCTURE, TO MAXIMIZE HUMAN Egg CONTENT SUBSTITUTE SHEET (RULE 26) STOP) SAMPLE START), SAMPLE 0 200 400 600 800 1000 1200 1400 1600 1800 TIME 3 SUBSTITUTE SHEET (RULE 26) B7H3 ELISA -o- ch8H9 -I:I- hu8H9 H1L1 -A— hu8H9 H1L2 —v— hu8H9 H2L1 -<>- hu8H9 H2L2 0.00001 0.0001 0.001 0.01 0.1 1 CONCENTRATION ) SUBSTITUTE SHEET (RULE 26) A B 4 1 3 0.8 $32 5%. 0-6 8 8 0.4 1 0.2 0 0 100 1000 10000 100000 0.01 0.1 1 10 DILUTION CONCENTRATION ) SUBSTITUTE SHEET (RULE 26) Egoga _ ., I-F4¢ «or no? Nor For 00? No? I-F4¢ w m N F o OOOOO x—x—x—x—x— H-ZTj gal-0.03% <1- C") N x—O 00000 «or H-ZTj gal-”Ea E.- me? \..“\\\\\-):-b~\“\\\\\ No? :44; <1- C") N‘— o gala-Ea 00000 x—x—x—x—x— <1- CV) N H-ZTj 00000 H'ZT? M we? EC: W\_n me? E No? IE Ea: E 58 E For E: mW 00? $8 E 205$ng Emor E For oer E :8 we? mor E For oer Fozaom Emmi NQZDOK 2%: ommmma SUBSTITUTE SHEET (RULE 26) 0.1pg/ml 1pg/ml § § 0 r 0 100 101 102 103104 Hu8H9H3L3scFv SUBSTITUTE SHEET (RULE 26) wwwwwwwwc?wwwwwwc?ww E—IE—IE—I OE—IE—IE—IE—IE—IE—IE—IE—IE—IE—IE—I ON ...................... >2: N ..xx.. ...x.. ...x.. ...... ...... ....x.. ..x.x.. ....... ....... ....... . .xxx.. .xxxx. :><°: :><: N :><: :><: >< N O N.OOOOO m.OmOOO 0.00000 m.OmOOO 0.00000 0.00000 0.00000 0.00000 OH.OOOOO OH.OOOOO OH.OOOOO ON.OOOOO ON.OOOOO ON.OOOOO ON.OOOOO ON.OOOOO ON.OOOOO SUBSTITUTE SHEET (RULE 26) OO N >-I>-I>-I>-I>-I >-I>-I>-I>-I>-I>-I>-I>-I>-I>-I E—IE—IE—IE—IE—IE—IE—IE—IE—iE—IE—IEIEIE—IE—IE—IE—I OO 9522.200 Om .0_n_ OOO m.mmOmO N.OOOOO 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 OH.OOOOO OH.OOOOO OH.OOOOO OO ON.OOOOO ON.OOOOO ON.OOOOO ON.OOOOO ON.OOOOO SUBSTITUTE SHEET (RULE 26)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462042457P | 2014-08-27 | 2014-08-27 | |
| PCT/US2015/047013 WO2016033225A2 (en) | 2014-08-27 | 2015-08-26 | Antibodies, compositions, and uses |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ729451A NZ729451A (en) | 2024-08-30 |
| NZ729451B2 true NZ729451B2 (en) | 2024-12-03 |
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