IP Library Granted Patent US 12,421,310
Granted Patent B2
US 12,421,310 · App. 17/041,100 · Granted Sep 23, 2025

CD47 binding agents

Inventor: William James Jonathan Finlay (Glasgow, GB)
Assignee: CENTESSA PHARMACEUTICALS (UK) LIMITED
C07K16/2803A61K45/06A61K47/6849A61K2039/505C07K2317/14C07K2317/24C07K2317/31C07K2317/565C07K2317/567C07K2317/622
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Quick Facts
Patent No.
US 12,421,310
App. No.
17/041,100
Granted
Sep 23, 2025
Kind
B2
Abstract

Provided herein are antibody molecules that bind specifically to CD47 and related nucleic acid molecules, vectors and host cells. Also provided herein are medical uses of such antibody molecules.

Claims (45)

1. An anti-CD47 antibody or an antigen-binding portion thereof, wherein the antibody or antigen-binding portion comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein

(a) the VH region amino acid sequence comprises HCDR1 of GYTFTNYAMH (SEQ ID NO:48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO:49) and HCDR3 of GGFRAMDY (SEQ ID NO:50); and the VL region amino acid sequence comprises LCDR1 of RSSQSLLHSNANTYLG (SEQ ID NO:55), LCDR2 of KGSNRFS (SEQ ID NO:52) and LCDR3 of FQASHVPYT (SEQ ID NO:53);

(b) the VH region amino acid sequence comprises HCDR1 of GYTFTNYAMH (SEQ ID NO:48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO:49) and HCDR3 of GGFRAMDY (SEQ ID NO:50); and the VL region amino acid sequence comprises LCDR1 of RSSQSLLHSNGNTYLG (SEQ ID NO:51), LCDR2 of KGSNRFS (SEQ ID NO:52) and LCDR3 of FQASHVPYT (SEQ ID NO:53);

(c) the VH region amino acid sequence comprises HCDR1 of GYTFTNYAMH (SEQ ID NO:48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO:49) and HCDR3 of GGFRAMDY (SEQ ID NO:50); and the VL region amino acid sequence comprises LCDR1 of RSSQSLLHSNAYNYLG (SEQ ID NO:56), LCDR2 of KGSNRFS (SEQ ID NO:52) and LCDR3 of FQASHVPYT (SEQ ID NO:53);

(d) the VH region amino acid sequence comprises HCDR1 of GYTFTNYAMH (SEQ ID NO:48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO:49) and HCDR3 of GGFRAMDY (SEQ ID NO:50); and the VL region amino acid sequence comprises LCDR1 of RSSQSLLHSNAYNYLG (SEQ ID NO:56), LCDR2 of KGSNRFS (SEQ ID NO:52) and LCDR3 of FQASQVPYT (SEQ ID NO:54);

(e) the VH region amino acid sequence comprises HCDR1 of GYTFTNYAMH (SEQ ID NO:48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO:49) and HCDR3 of GGFRAMDY (SEQ ID NO:50); and the VL region amino acid sequence comprises LCDR1 of RSSQSLLHSNANTYLG (SEQ ID NO:55), LCDR2 of KGSNRFS (SEQ ID NO:52) and LCDR3 of FQASQVPYT (SEQ ID NO:54);

(f) the VH region amino acid sequence comprises HCDR1 of GYTFTNYAMH (SEQ ID NO:48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO:49) and HCDR3 of GGFRAMDY (SEQ ID NO:50); and the VL region amino acid sequence comprises LCDR1 of RSSQSLLHSNGNTYLG (SEQ ID NO:51), LCDR2 of KGSNRFS (SEQ ID NO:52) and LCDR3 of FQASQVPYT (SEQ ID NO:54); or

(g) the VH region amino acid sequence comprises HCDR1 of GYSFTNYNIH (SEQ ID NO:57), HCDR2 of MGTIYPGNSDTSYNPSFQG (SEQ ID NO: 61) and HCDR3 of GGVRAMDY (SEQ ID NO:62); and the VL region amino acid sequence comprises LCDR1 of RSSQSLLHSNGNTYLG (SEQ ID NO:51), LCDR2 of KGSNRFS (SEQ ID NO:52) and LCDR3 of MQASQVPYT (SEQ ID NO:63).

2. The antibody or antigen-binding portion of claim 1 , wherein

(a) the VH region amino acid sequence comprises SEQ ID NO: 1 and the VL region amino acid sequence comprises SEQ ID NO:2;

(b) the VH region amino acid sequence comprises SEQ ID NO:3 and the VL region amino acid sequence comprises SEQ ID NO:4;

(c) the VH region amino acid sequence comprises SEQ ID NO:5 and the VL region amino acid sequence comprises SEQ ID NO:6;

(d) the VH region amino acid sequence comprises SEQ ID NO:7 and the VL region amino acid sequence comprises SEQ ID NO:8;

(e) the VH region amino acid sequence comprises SEQ ID NO:9 and the VL region amino acid sequence comprises SEQ ID NO: 10;

(f) the VH region amino acid sequence comprises SEQ ID NO: 11 and the VL region amino acid sequence comprises SEQ ID NO: 12;

(g) the VH region amino acid sequence comprises SEQ ID NO: 13 and the VL region amino acid sequence comprises SEQ ID NO: 14; or

(h) the VH region amino acid sequence comprises SEQ ID NO:15 and the VL region amino acid sequence comprises SEQ ID NO: 16.

3. The antibody or antigen-binding portion of claim 1 , wherein the antibody is humanized or chimeric.

4. The antibody or antigen-binding portion of claim 1 , wherein the VH region, the VL region, or both the VH and the VL region comprise one or more human framework region amino acid sequences.

5. The antibody or antigen-binding portion of claim 1 , wherein the VH region, the VL region, or both the VH and the VL region comprise a human variable region framework scaffold amino acid sequence into which the CDRs have been inserted.

6. The antibody or antigen-binding portion of claim 1 , wherein the VH region comprises an IGHV5-51 or IGHV1-3 human germline scaffold amino acid sequence into which the HCDR1, HCDR2 and HCDR3 amino acid sequences have been inserted.

7. The antibody or antigen-binding portion of claim 1 , wherein the VL region comprises an IGKV2-28 human germline scaffold amino acid sequence into which the LCDR1, LCDR2 and LCDR3 amino acid sequences have been inserted.

8. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion comprises an immunoglobulin constant region.

9. The antibody or antigen-binding portion of claim 8 , wherein the immunoglobulin constant region is IgG, IgE, IgM, IgD, IgA or IgY.

10. The antibody or antigen-binding portion of claim 9 , wherein the immunoglobulin constant region is IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2.

11. The antibody or antigen-binding portion of claim 8 , wherein the immunoglobulin constant region is a wild-type human IgG4 constant region, a human IgG4 constant region comprising the amino acid substitution S228P, a wild-type human IgG1 constant region, a human IgG1 constant region comprising the amino acid substitutions L234A, L235A and G237A or a wild-type human IgG2 constant region.

12. The antibody or antigen-binding portion of claim 8 , wherein the immunoglobulin constant region comprises any one of SEQ ID NOS:17-23.

13. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is an Fab, an Fab′, an F(ab′)2, an Fv, an scFv, a maxibody, a minibody, an intrabody, a diabody, a triabody, a tetrabody, or a bis-scFv.

14. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is monoclonal.

15. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is tetrameric, tetravalent or multispecific.

16. An immunoconjugate comprising the antibody or antigen-binding portion of claim 1 , linked to a therapeutic agent.

17. A pharmaceutical composition comprising the antibody or antigen-binding portion of claim 1 and a pharmaceutically acceptable carrier.

18. A nucleic acid molecule encoding both the VH and the VL region amino acid sequences of the antibody or antigen-binding portion of claim 1 .

19. An expression vector comprising the nucleic acid molecule of claim 18 .

20. An individual recombinant host cell comprising the nucleic acid molecule of claim 18 .

21. A method of producing an anti-CD47 antibody or an antigen-binding portion thereof, the method comprising:

culturing the recombinant host cell of claim 20 under conditions whereby the nucleic acid molecule is expressed, thereby producing the antibody or antigen-binding portion; and

isolating the antibody or antigen-binding portion from the host cell or culture.

22. A method for enhancing an immune response in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding portion of claim 1 , thereby enhancing the immune response.

23. The method of claim 22 , wherein the subject has a cancer, an autoimmune disease, an inflammatory disease, a cardiovascular disease or a fibrotic disease.

24. The method of claim 23 , wherein the cancer is gastrointestinal stromal cancer (GIST), pancreatic cancer, melanoma, breast cancer, lung cancer, bronchial cancer, colorectal cancer, prostate cancer, stomach cancer, ovarian cancer, urinary bladder cancer, brain or central nervous system cancer, peripheral nervous system cancer, esophageal cancer, cervical cancer, uterine or endometrial cancer, cancer of the oral cavity or pharynx, liver cancer, kidney cancer, testicular cancer, biliary tract cancer, small bowel or appendix cancer, salivary gland cancer, thyroid gland cancer, adrenal gland cancer, osteosarcoma, chondrosarcoma or cancer of hematological tissues.

25. The method of claim 23 , wherein the autoimmune disease or the inflammatory disease is arthritis, asthma, multiple sclerosis, psoriasis, Crohn's disease, inflammatory bowel disease, lupus, Grave's disease, Hashimoto's thyroiditis or ankylosing spondylitis.

26. The method of claim 23 , wherein the cardiovascular disease is coronary heart disease or atherosclerosis.

27. The method of claim 23 , wherein the fibrotic disease is myocardial infarction, angina, osteoarthritis, pulmonary fibrosis, cystic fibrosis, bronchitis or asthma.

28. An anti-CD47 antibody or an antigen-binding portion thereof, wherein the antibody or antigen-binding portion comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the VH region amino acid sequence comprises HCDR1 of GYTFTNYAMH (SEQ ID NO:48), HCDR2 of MGTIYPGNDDTKYNQKFQG (SEQ ID NO:49) and HCDR3 of GGFRAMDY (SEQ ID NO:50); and the VL region amino acid sequence comprises LCDR1 of RSSQSLLHSNANTYLG (SEQ ID NO:55), LCDR2 of KGSNRFS (SEQ ID NO:52) and LCDR3 of FQASHVPYT (SEQ ID NO:53).

Assignments (6)
RELEASE OF SECURITY INTEREST Recorded Jun 24, 2026
From: OXFORD FINANCE LLC
To: CENTESSA PHARMACEUTICALS (UK) LIMITED
Reel/Frame 075069/0879 →
SECURITY INTEREST Recorded Dec 31, 2024
From: CENTESSA PHARMACEUTICALS (UK) LIMITED
To: OXFORD FINANCE LLC
Reel/Frame 069708/0039 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 28, 2023
From: ULTRAHUMAN TWO LIMITED
To: CENTESSA PHARMACEUTICALS (UK) LIMITED
Reel/Frame 065058/0045 →
CHANGE OF REGISTERED OFFICE ADDRESS Recorded May 20, 2022
From: ULTRAHUMAN TWO LIMITED
To: ULTRAHUMAN TWO LIMITED
Reel/Frame 060135/0770 →
SECURITY INTEREST Recorded Oct 4, 2021
From: APCINTEX LIMITED; JANPIX LIMITED; CAPELLA BIOSCIENCE LTD; LOCKBODY THERAPEUTICS LTD; ULTRAHUMAN TWO LIMITED; ULTRAHUMAN FOUR LIMITED; MORPHOGEN-IX LIMITED; OREXIA THERAPEUTICS LIMITED; CARDIOKINE BIOPHARMA LLC; PALLADIO BIOSCIENCES, INC.; PEARLRIVER BIO GMBH; Z FACTOR LIMITED
To: COCOON SA LLC
Reel/Frame 057710/0082 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 29, 2020
From: FINLAY, WILLIAM JAMES JONATHAN
To: ULTRAHUMAN TWO LIMITED
Reel/Frame 053913/0676 →
Priority Claims (2)
GB 1804860 · Mar 27, 2018 · national
GB 1813693 · Aug 22, 2018 · national
Continuity (1)
Related Publication 20210179711A1 · Jun 17, 2021
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