Compositions and methods comprising anti-nrp2 antibodies

Patent metadata

Field	Value
Publication number	US-2024092917-A1
Application number	US-202318477113-A
Country	US
Kind code	A1
Filing date	Sep 28, 2023
Priority date	Oct 3, 2019
Publication date	Mar 21, 2024
Grant date	—

Abstract

Provided are affinity matured and humanized antibodies and antigen-binding fragments thereof that specifically bind to human neuropilin-2 (NRP2) polypeptides, including those that modulate binding interactions between human NRP2 and at least one NRP2 ligand, and which thereby modulate subsequent NRP2-mediated downstream signaling events, including related therapeutic compositions and methods for modulating NRP2 activity and treating diseases such as NRP2-associated diseases.

First claim

1 . A therapeutic composition, comprising at least one antibody or antigen-binding fragment thereof that specifically binds to a human neuropilin-2 (NRP2) polypeptide (anti-NRP2 antibody), wherein the at least one antibody or antigen-binding fragment thereof comprises:
a heavy chain variable region (V H ) sequence that comprises complementary determining region V H CDR1, V H CDR2, and V H CDR3 sequences; and a light chain variable region (V L ) sequence that comprises complementary determining region V L CDR1, V L CDR2, and V L CDR3 sequences, wherein: the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 31, 32, and 81, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 82, 5, and 83, respectively.

2 . The therapeutic composition of claim 2 , wherein:
the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 31-33, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 34-36, respectively, including variants thereof; or the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 37-39, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 40-42, respectively, including variants thereof.

3 . The therapeutic composition of claim 1 , wherein:
the V H sequence comprises a sequence at least 95% identical to a SEQ ID NO: 53, and the V L sequence comprises a sequence at least 95% identical to SEQ ID NO: 54; or the V H sequence comprises a sequence at least 95% identical to SEQ ID NO: 55, and the V L sequence comprises a sequence at least 95% identical to SEQ ID NO: 56.

4 . (canceled)

5 . The therapeutic composition of claim 3 , wherein:
the V H sequence comprises SEQ ID NO: 53, and the V L sequence comprises SEQ ID NO: 54; or the V H sequence comprises SEQ ID NO: 55, and the V L sequence comprises SEQ ID NO: 56.

6 - 44 . (canceled)

45 . The therapeutic composition of claim 1 , wherein the at least one antibody or antigen-binding fragment thereof comprises an IgA (including subclasses IgA1 and IgA2), IgD, IgE, IgG (including subclasses IgG1, IgG2, IgG3, and IgG4), or IgM Fc domain, optionally a human Fc domain, or a hybrid and/or variant thereof.

46 . The therapeutic composition of claim 45 , wherein the at least one antibody or antigen-binding fragment thereof comprises an IgG1 or IgG3 Fc domain.

47 . The therapeutic composition of claim 45 , wherein the at least one antibody or antigen-binding fragment thereof comprises an IgG2 or IgG4 Fc domain.

48 . The therapeutic composition of claim 47 , wherein the at least one antibody or antigen-binding fragment thereof comprises an IgG1 or IgG4 Fc domain, optionally selected from SEQ ID NOs: 144-148.

49 . The therapeutic composition of claim 1 , wherein the at least one antibody or antigen-binding fragment thereof comprises a modified IgG1 or IgG4 Fc domain which has altered binding to FcRn, optionally wherein the modified IgG1 or IgG4 Fc domain comprises any one or more of YD (M252Y/T256D), DQ (T256D/T307Q), DW (T256D/T307W), YTE (M252Y/S254T/T256E), AAA (T307A/E380A/N434A), LS (M428L/N434S), M252Y, T256D/E, K288D/N, T307Q/W, E380C, N434F/Y, and/or Y436H/N/W mutations (EU numbering), including combinations thereof.

50 . The therapeutic composition of claim 1 , wherein the at least one antibody or antigen-binding fragment thereof is a monoclonal antibody and/or a humanized antibody.

51 . The therapeutic composition of claim 1 , wherein the at least one antibody or antigen-binding fragment thereof is an Fv fragment, a single chain Fv (scFv) polypeptide, a minibody, or a unibody.

52 . The therapeutic composition of claim 1 , wherein the composition has a purity of at least about 80%, 85%, 90%, 95%, 98%, or 99% on a protein basis with respect to the at least one antibody or antigen-binding fragment, and is substantially aggregate-free.

53 . The therapeutic composition of claim 52 , wherein the therapeutic composition is substantially endotoxin-free.

54 . The therapeutic composition of claim 1 , wherein the therapeutic composition is a sterile, injectable solution, optionally suitable for intravenous, intramuscular, subcutaneous, or intraperitoneal administration.

55 - 150 . (canceled)

151 . The therapeutic composition of claim 1 , which is a concentrated lyophilized composition.

Assignees

• Atyr Pharma Inc

Inventors

• Burman Luke
• Chong Yeeting
• Greene Leslie Ann
• King David
• Xu Zhiwen
• Adams Ryan Andrew

Classifications

• A61K39/001103

  Receptors for growth factors · CPC title

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/04

  specific for metastasis · CPC title