CDCP1 antibodies and antibody drug conjugates

Patent metadata

Field	Value
Publication number	US-12371507-B2
Application number	US-201917292257-A
Country	US
Kind code	B2
Filing date	Nov 7, 2019
Priority date	Nov 9, 2018
Publication date	Jul 29, 2025
Grant date	Jul 29, 2025

Abstract

The present disclosure provides materials and methods for CUB domain-containing protein 1 (CDCP1)-targeted therapy.

First claim

What is claimed is:

1. An isolated antibody, or antigen-binding fragment thereof, that specifically binds CDCP1, comprising:
(i) a VH that comprises:
(a) a CDRH1 comprising the amino acid sequence of SEQ ID NO:2,
(b) a CDRH2 comprising the amino acid sequence of SEQ ID NO:3; and
(c) a CDRH3 comprising the amino acid sequence of SEQ ID NO:27;

and (ii) a VL that comprises:
(a) a CDRL1 comprising the amino acid sequence of SEQ ID NO:12,
(b) a CDRL2 comprising the amino acid sequence of SEQ ID NO:13; and
(c) a CDRL3 comprising the amino acid sequence of SEQ ID NO:31.

2. An antibody drug conjugate comprising an antibody, or antigen-binding fragment thereof, that specifically binds CUB Domain-Containing Protein-1 (CDCP1), wherein the antibody is conjugated to a drug moiety, wherein the antibody, or antigen-binding fragment thereof, comprises:
(i) a heavy chain variable region (VH) that comprises:
(a) a VH complementarity determining region one (CDRH1) comprising the amino acid sequence of SEQ ID NO: 2,
(b) a VH complementarity determining region two (CDRH2) comprising the amino acid sequence of SEQ ID NO: 3, and
(c) a VH complementarity determining region three (CDRH3) comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 27, SEQ ID NO: 4, SEQ ID NO: 40 and SEQ ID NO: 45,

and (ii) a light chain variable region (VL) that comprises:
(a) a VL complementarity determining region one (CDRL1) comprising the amino acid sequence of SEQ ID NO: 12,
(b) a VL complementarity determining region two (CDRL2) comprising the amino acid sequence of SEQ ID NO: 13, and
(c) a VL complementarity determining region three (CDRL3) comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 31 and SEQ ID NO:14.

3. The antibody drug conjugate of claim 2 , wherein the antibody comprises a VH that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 26, and a VL that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 30.

4. The antibody drug conjugate of claim 2 , wherein the antibody comprises a VH that comprises the amino acid sequence of SEQ ID NO: 26 and a VL that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 36.

5. The antibody drug conjugate of claim 2 , wherein the antibody comprises a heavy chain comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID No: 29 and a light chain comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 37 or SEQ ID NO: 32.

6. The antibody drug conjugate of claim 5 , wherein the antibody comprises a heavy chain that comprises the amino acid sequence of SEQ ID NO: 29 and a light chain that comprises the amino acid sequence of SEQ ID NO: 37.

7. The antibody drug conjugate of claim 2 , wherein the antibody comprises a heavy chain comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID No: 33 and a light chain comprising an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 38 or SEQ ID NO: 34.

8. The antibody drug conjugate of claim 7 , wherein the antibody comprises a heavy chain that comprises the amino acid sequence of SEQ ID NO: 33 and a light chain that comprises the amino acid sequence of SEQ ID NO: 38.

Assignees

• Beth Israel Deaconess Medical Ct Inc
• Pfizer
• Univ Cornell

Inventors

• Cantley Lewis C
• Soltoff Stephen P
• Emerling Brooke M
• Poulogiannis Georgios
• Hodakoski Cindy M
• Liu Hui
• Apostolou Irina
• Bates Brian Gaither
• Marquette Kimberly Ann
• Bennett Eric M
• Mosyak Lidia
• Tchistiakova Lioudmila G
• Rosfjord Edward Christian
• Rondon Isaac J
• Huang Chao Bai

Classifications

• C07K2317/77

  Internalization into the cell · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/71

  Decreased effector function due to an Fc-modification · CPC title

• C07K2317/567

  Framework region [FR] · CPC title