IP Library › Granted Patent US 12,269,891
Granted Patent B2
US 12,269,891 · App. 17/561,448 · Granted Apr 8, 2025

Agonistic anti-tumor necrosis factor receptor 2 antibodies

Inventor: Denise L. Faustman (Boston, MA)
Assignee: The General Hospital Corporation
C07K16/2878A61K38/191A61K39/3955A61P37/06G01N33/6854C07K2317/34C07K2317/622C07K2317/75C07K2317/92G01N2333/7151
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Quick Facts
Patent No.
US 12,269,891
App. No.
17/561,448
Granted
Apr 8, 2025
Kind
B2
Abstract

The invention provides agonistic TNFR2 antibodies and antigen-binding fragments thereof and encompasses the use of these antibodies as therapeutics to promote the proliferation of regulatory T cells (T-reg) for the treatment of immunological diseases. Antibodies of the invention can be used to potentiate the T-reg-mediated deactivation of self- and allergen-reactive T- and B-lymphocytes, and can thus be used to treat a wide variety of indications, including autoimmune diseases, allergic reactions, asthma, graft-versus-host disease, and allograft rejection, among others.

Claims (21)

1. An antibody or antigen-binding fragment thereof that specifically binds human tumor necrosis factor receptor 2 (TNFR2) comprising:

(a) means for binding an epitope within human TNFR2 bound by antibody 8E6.D1 (ATCC® accession number PTA-127418); and

(b) an Fc region,

wherein the antibody or antigen-binding fragment thereof does not bind an epitope within human TNFR2 comprising amino acids 142-146 of SEQ ID NO: 366.

2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof specifically binds an epitope within human TNFR2 comprising amino acids 56-60 of SEQ ID NO: 366.

3. The antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment thereof specifically binds:

(a) an epitope within amino acids 48-67 of SEQ ID NO: 366; and/or

(b) an epitope within human TNFR2 comprising amino acids 56-60 of SEQ ID NO: 366 with a K D of less than about 10 nM.

4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof does not bind another tumor necrosis factor receptor (TNFR) superfamily member.

5. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof specifically binds a polypeptide having the amino acid sequence of SEQ ID NO: 346 or 367.

6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody or antigen-binding fragment thereof.

7. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody comprises an immunoglobulin of subtype IgG.

8. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is antibody 8E6.D1 (ATCC® accession number PTA-127418).

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

10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition further comprises a therapeutic agent.

11. The pharmaceutical composition of claim 10 , wherein the therapeutic agent is TNFα or Bacillus Calmette-Guérin (BCG).

12. A kit comprising the antibody or antigen-binding fragment thereof of claim 1 .

13. An antibody or antigen-binding fragment thereof that specifically binds human TNFR2, wherein the antibody or antigen-binding fragment thereof is antibody 8E6.D1 (ATCC® accession number PTA-127418), wherein the antibody or antigen-binding fragment thereof specifically binds:

(a) an epitope within human TNFR2 comprising amino acids 56-60 of SEQ ID NO: 366; and/or

(b) a polypeptide having the amino acid sequence of SEQ ID NO: 346 or 367;

and wherein the antibody or antigen-binding fragment thereof does not bind an epitope within human TNFR2 comprising amino acids 142-146 of SEQ ID NO: 366.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 7, 2022
From: FAUSTMAN, DENISE L.
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 059528/0932 →
Continuity (3)
Continuation 15755404
Provisional Application 62211345 · Aug 28, 2015
Related Publication 20220112299A1 · Apr 14, 2022
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