Granted Patent B2

US 12,509,521 · App. 17/294,008 · Granted Dec 30, 2025

Inventor: Denise L. Faustman (Boston, MA)

Assignee: The General Hospital Corporation

C07K16/2875C07K16/30C12N15/86C07K2317/33C07K2317/565

Abstract

Claims (35)

1 . An isolaed humanized or chimeric antibody or antigen-binding fragment thereof that binds human tumor necrosis factor receptor 2 (TNFR2), wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs):

(i) a complementarity determining region-heavy chain 1 (CDR-H1) comprising the amino acid sequence GYTFTDYNI (SEQ ID NO: 3) or GYTFTDYNL (SEQ ID NO: 4);

(ii) a CDR-H2 comprising the amino acid sequence INPNYDST (SEQ ID NO: 10);

(iii) a CDR-H3 comprising the amino acid sequence CARGNSWYFDV (SEQ ID NO: 11);

(iv) a complementarity determining region-light chain 1 (CDR-L1) comprising the amino acid sequence SSVRY (SEQ ID NO: 12);

(v) a CDR-L2 comprising the amino acid sequence LTS; and

(vi) a CDR-L3 comprising the amino acid sequence CQQWSSNPLT (SEQ ID NO: 13).

2 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof has an IgG3 or IgG4 isotype.

3 . The antibody or antigen-binding fragment thereof of claim 1 , wherein:

(a) the antibody or antigen-binding fragment thereof has an IgG3 isotype;

(b) the antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (V H ) comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 14; or

(c) the antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (V H ) comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 15.

4 . The antibody or antigen-binding fragment thereof of claim 3 , wherein

(i) the CDR-H1 has the amino acid sequence GYTFTDYNI (SEQ ID NO: 3);

(ii) the antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (V H ) comprising the amino acid sequence of SEQ ID NO: 14;

(iii) the CDR-H1 has the amino acid sequence GYTFTDYNL (SEQ ID NO: 4); or

(iv) the antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (V H ) comprising the amino acid sequence of SEQ ID NO: 15.

5 . A construct comprising a first polypeptide domain and a second polypeptide domain, wherein the first polypeptide domain and the second polypeptide domain each independently comprise a single-chain polypeptide comprising the antibody or antigen-binding fragment thereof of claim 1 .

6 . The construct of claim 5 , wherein the first polypeptide domain and the second polypeptide domain are bound by a covalent linker, wherein the covalent linker comprises an amide bond or a disulfide bond.

7 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 or a construct comprising the antibody or antigen-binding fragment thereof of claim 1 , and a pharmaceutically acceptable carrier or excipient.

8 . The pharmaceutical composition of claim 7 , wherein said antibody or antigen-binding fragment thereof is present in the pharmaceutical composition in an amount of from about 0.001 mg/ml to about 100 mg/ml.

9 . The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition further comprises an additional therapeutic agent.

10 . The pharmaceutical composition of claim 9 , wherein the additional therapeutic agent is an immunotherapy agent.

11 . A kit comprising the antibody or antigen-binding fragment thereof of claim 1 or a construct comprising the antibody or antigen-binding fragment thereof of claim 1 .

12 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a human IgG1 or IgG2 heavy chain constant 1 (CH1) domain comprising a deletion or substitution at cysteine residue 127 according to the Kabat numbering scheme.

13 . The antibody or antigen-binding fragment thereof of claim 12 , wherein the antibody or antigen-binding fragment thereof comprises a human IgG1 or IgG2 CH1 domain comprising a C127S mutation according to the Kabat numbering scheme.

14 . The antibody or antigen-binding fragment thereof of claim 12 , wherein the antibody or antigen-binding fragment thereof comprises:

(a) a human IgG1 CH1 domain comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 6; or

(b) a human IgG1 CH1 domain comprising the amino acid sequence of SEQ ID NO: 7.

15 . The antibody or antigen-binding fragment thereof of claim 12 , wherein the antibody or antigen-binding fragment thereof comprises:

(a) a human IgG2 CH1 domain comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 8; or

(b) a human IgG2 CH1 domain comprising the amino acid sequence of SEQ ID NO: 9.

16 . The antibody or antigen-binding fragment thereof of claim 14 , wherein the human IgG1 CH1 domain has the amino acid sequence of SEQ ID NO: 7.

17 . The antibody or antigen-binding fragment thereof of claim 15 , wherein the human IgG2 CH1 domain has the amino acid sequence of SEQ ID NO: 9.

18 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a framework region comprising the amino acid sequence of TJDJSJJJX 1 YX 2 X 3 LJX 4 LJS (SEQ ID NO: 5) or an amino acid sequence comprising 10 or more of the residues of SEQ ID NO: 5, wherein each J is independently a naturally occurring amino acid; each X 1 is independently A, V, or F; each X 2 is independently M or I; each X 3 is independently E or Q; and each X 4 is independently S or R.

Assignments (1)

Continuity (2)

References Cited (400)