Granted Patent
B2
US 12,692,315 · App. 18/128,928 · Granted Jul 28, 2026
Bispecific antibodies comprising an NRP1 binding domain and methods of use thereof
Assignee:
Pinetree Therapeutics, Inc.
C07K16/2863A61P35/00C07K16/28A61K2039/505C07K2317/31C07K2317/622C07K2317/73C07K2317/76C07K2317/77C07K2317/92
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Abstract
The present disclosure provides bispecific antibodies, and compositions and methods of treating cancer incorporating said bispecific antibodies. The bispecific antibodies include a polypeptide comprising an EGFR-binding domain and a neuropilin (NRP1)-specific binding domain at the C-terminal end. Monoclonal antibodies that specifically bind NRP1 are also provided.
Claims (19)
1 . A bispecific antibody comprising a first binding domain that binds to human neuropilin-1 receptor (NRP1) and a second binding domain that binds to epidermal growth factor receptor (EGFR), wherein the first binding domain comprises:
(i) an antibody heavy chain variable (VH) domain comprising CDR1, CDR2 and CDR3 regions (HCDR1, HCDR2 and HCDR3, respectively), wherein HCDR1 consists of the sequence shown in SEQ ID NO: 79, HCDR2 consists of the sequence shown in SEQ ID NO: 80, and HCDR3 consists of the sequence shown in SEQ ID NO: 81s; and
(ii) an antibody light chain variable (VL) domain comprising CDR1, CDR2 and CDR3 regions (LCDR1, LCDR2 and LCDR3, respectively), wherein LCDR1 consists of the sequence shown in SEQ ID NO: 85, LCDR2 consists of the sequence shown in SEQ ID NO: 88, and LCDR3 consists of the sequence shown in SEQ ID NO: 89; and wherein the second binding domain comprises:
(i) an antibody heavy chain variable (VH) domain comprising CDR1, CDR2 and CDR3 regions (HCDR1, HCDR2 and HCDR3, respectively), wherein HCDR1 consists of the sequence shown in SEQ ID NO: 71, HCDR2 consists of the sequence shown in SEQ ID NO: 72, and HCDR3 consists of the sequence shown in SEQ ID NO: 73; and
(ii) an antibody light chain variable (VL) domain comprising CDR1, CDR2 and CDR3 regions (LCDR1, LCDR2 and LCDR3, respectively), wherein LCDR1 consists of the sequence shown in SEQ ID NO: 74, LCDR2 consists of the sequence shown in SEQ ID NO: 75, and LCDR3 consists of the sequence shown in SEQ ID NO: 76.
2 . The bispecific antibody of claim 1 , wherein the second binding domain is comprised of an N-terminal EGFR-binding heavy chain variable domain (VH) and a heavy chain constant 1 domain (CH1), and the first binding domain is comprised of a C-terminal NRP1-binding single chain variable fragment (scFv), wherein the N-terminal variable heavy chain (VH) and the C-terminal scFv binding domains are at opposite ends of a contiguous sequence.
3 . The bispecific antibody of claim 2 , wherein the second binding domain further comprises a heavy chain constant 2 domain (CH2) and a heavy chain constant 3 domain (CH3).
4 . The bispecific antibody of claim 3 , wherein the C-terminal NRP1-binding scFv comprises a light chain variable domain (VL) connected to a heavy chain variable domain (VH) by a flexible linker peptide.
5 . The bispecific antibody of claim 4 , which further comprises a corresponding EGFR binding light chain variable domain (VL) and light chain constant domain (CL), wherein the bispecific antibody is comprised of two polypeptides.
6 . A bispecific antibody, comprising:
a first binding domain that binds to human neuropilin-1 receptor (NRP1); and
a second binding domain that binds to epidermal growth factor receptor (EGFR), wherein the first binding domain that binds human NRP1 comprises a VH domain comprising the sequence shown in SEQ ID NO: 77 and a VL domain comprising the sequence shown in SEQ ID NO: 78, and the second binding domain that binds EGFR comprises a VH domain comprising the sequence shown in SEQ ID NO: 69 and a VL domain comprising the sequence shown in SEQ ID NO: 70.
7 . The bispecific antibody of claim 1 , wherein the first binding domain comprises a VH domain comprising the sequence shown in SEQ ID NO: 77 and a VL domain comprising the sequence shown in SEQ ID NO: 78; and the second binding domain comprises a VH domain comprising the sequence shown in SEQ ID NO: 69 and a VL domain comprising the sequence shown in SEQ ID NO: 70.
8 . The bispecific antibody of claim 1 , wherein the first binding domain and the second binding domain comprise a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 11.
9 . The bispecific antibody of claim 8 , wherein the heavy chain is paired with a light chain comprising the amino acid sequence shown SEQ ID NO: 12.
10 . A pharmaceutical composition comprising the bispecific antibody of claim 1 .
11 . A polynucleotide encoding the bispecific antibody of claim 1 .
12 . The polynucleotide of claim 11 , wherein the bispecific antibody comprises a heavy chain polypeptide encoded by the polynucleotide sequence set forth in SEQ ID NO: 24.
13 . The polynucleotide of claim 12 , wherein the polynucleotide sequence is inserted into a vector for protein expression.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 9, 2026
From: REINSHAGEN, CLEMENS; CHOI, SUNG HUGH; ROSSOMANDO, ANTHONY JOHN; JEONG, EUIJOON
To: PINETREE THERAPEUTICS, INC.
Reel/Frame 074327/0218 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 7, 2023
From: SONG, HO-JUHN
To: PINETREE THERAPEUTICS, INC.
Reel/Frame 064182/0481 →
Continuity (3)
Provisional Application
63325317
· Mar 30, 2022
Provisional Application
63325312
· Mar 30, 2022
Related Publication
20240101682A1
· Mar 28, 2024
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