Therapeutic compositions comprising anti-NRP2 antibodies
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.
1. A therapeutic composition, comprising a physiologically-acceptable carrier and 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: 19-21, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 22-24, respectively.
2. The therapeutic composition of claim 1 , wherein: the V H sequence comprises a sequence at least 95% identical to SEQ ID NO: 49, and the V L sequence comprises a sequence at least 95% identical to SEQ ID NO: 50.
3. 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), IgM Fc domain, or variant thereof, optionally wherein the Fc domain is a human Fc domain.
4. The therapeutic composition of claim 3 , wherein the at least one antibody or antigen-binding fragment thereof comprises an IgG1 or IgG3 Fc domain.
5. The therapeutic composition of claim 3 , wherein the at least one antibody or antigen-binding fragment thereof comprises an IgG2 or IgG4 Fc domain.
6. The therapeutic composition of claim 5 , 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.
7. 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).
8. The therapeutic composition of claim 1 , wherein the at least one antibody or antigen-binding fragment thereof is a monoclonal antibody, optionally a humanized antibody.
9. 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.
10. The therapeutic composition of claim 1 , wherein the composition has a purity of at least about 80% on a protein basis with respect to the at least one antibody or antigen-binding fragment, and is substantially aggregate-free.
11. The therapeutic composition of claim 1 , wherein the therapeutic composition is substantially endotoxin-free.
12. The therapeutic composition of claim 1 , wherein the therapeutic composition is a sterile, injectable solution, optionally suitable for intravenous, intramuscular, subcutaneous, or intraperitoneal administration.
13. The therapeutic composition of claim 1 , which is a concentrated lyophilized composition.