Anti-CCR7 antibody drug conjugates

Patent metadata

Field	Value
Publication number	US-12180291-B2
Application number	US-202318164519-A
Country	US
Kind code	B2
Filing date	Feb 3, 2023
Priority date	Feb 3, 2017
Publication date	Dec 31, 2024
Grant date	Dec 31, 2024

Abstract

This application discloses anti-CCR7 antibodies, antigen binding fragments thereof, and antibody drug conjugates of said antibodies or antigen binding fragments. The invention also relates to methods of treating or preventing cancer using the antibodies, antigen binding fragments, and antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents.

First claim

We claim:

1. A nucleic acid that encodes an antibody or antigen binding fragment comprising
a. a heavy chain variable region that comprises an HCDR1 (Heavy Chain Complementarity Determining Region 1) of SEQ ID NO:1, an HCDR2 (Heavy Chain Complementarity Determining Region 2) of SEQ ID NO:2, and an HCDR3 (Heavy Chain Complementarity Determining Region 3) of SEQ ID NO:3; and a light chain variable region that comprises an LCDR1 (Light Chain Complementarity Determining Region 1) of SEQ ID NO:17, an LCDR2 (Light Chain Complementarity Determining Region 2) of SEQ ID NO: 18, and an LCDR3 (Light Chain Complementarity Determining Region 3) of SEQ ID NO: 19;
b. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO:4, an HCDR2 of SEQ ID NO:5, and an HCDR3 of SEQ ID NO:6; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:20, an LCDR2 of SEQ ID NO:21, and an LCDR3 of SEQ ID NO:22;
c. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO:7, an HCDR2 of SEQ ID NO:8, and an HCDR3 of SEQ ID NO:9; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:23, an LCDR2 of SEQ ID NO:24, and an LCDR3 of SEQ ID NO:25;
d. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 10, an HCDR2 of SEQ ID NO:11, and an HCDR3 of SEQ ID NO:12; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:26, an LCDR2 of SEQ ID NO: 27, and an LCDR3 of SEQ ID NO:28;
e. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 33, an HCDR2 of SEQ ID NO:34, and an HCDR3 of SEQ ID NO:35; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:49, an LCDR2 of SEQ ID NO: 50, and an LCDR3 of SEQ ID NO:51;
f. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 36, an HCDR2 of SEQ ID NO:37, and an HCDR3 of SEQ ID NO:38; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:52, an LCDR2 of SEQ ID NO: 53, and an LCDR3 of SEQ ID NO:54;
g. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 39, an HCDR2 of SEQ ID NO:40, and an HCDR3 of SEQ ID NO:41; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:55, an LCDR2 of SEQ ID NO: 56, and an LCDR3 of SEQ ID NO:57;
h. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 42, an HCDR2 of SEQ ID NO:43, and an HCDR3 of SEQ ID NO:44; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:58, an LCDR2 of SEQ ID NO: 59, and an LCDR3 of SEQ ID NO:60;
i. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 65, an HCDR2 of SEQ ID NO:66, and an HCDR3 of SEQ ID NO:67; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:81, an LCDR2 of SEQ ID NO: 82, and an LCDR3 of SEQ ID NO:83;
j. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 68, an HCDR2 of SEQ ID NO:69, and an HCDR3 of SEQ ID NO:70; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:84, an LCDR2 of SEQ ID NO: 85, and an LCDR3 of SEQ ID NO:86;
k. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 71, an HCDR2 of SEQ ID NO:72, and an HCDR3 of SEQ ID NO:73; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:87, an LCDR2 of SEQ ID NO: 88, and an LCDR3 of SEQ ID NO:89;
l. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 74, an HCDR2 of SEQ ID NO:75, and an HCDR3 of SEQ ID NO:76; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:90, an LCDR2 of SEQ ID NO: 91, and an LCDR3 of SEQ ID NO:92;
m. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 596, an HCDR2 of SEQ ID NO:597, and an HCDR3 of SEQ ID NO:598; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:612, an LCDR2 of SEQ ID NO: 613, and an LCDR3 of SEQ ID NO:614;
n. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 599, an HCDR2 of SEQ ID NO:600, and an HCDR3 of SEQ ID NO:601; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:615, an LCDR2 of SEQ ID NO: 616, and an LCDR3 of SEQ ID NO:617;
o. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 602, an HCDR2 of SEQ ID NO:603, and an HCDR3 of SEQ ID NO:604; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:618, an LCDR2 of SEQ ID NO: 619, and an LCDR3 of SEQ ID NO:620; or
p. a heavy chain variable region that comprises an HCDR1 of SEQ ID NO: 605, an HCDR2 of SEQ ID NO:606, and an HCDR3 of SEQ ID NO:607; and a light chain variable region that comprises an LCDR1 of SEQ ID NO:621, an LCDR2 of SEQ ID NO: 622, and an LCDR3 of SEQ ID NO:623.

2. The nucleic acid of claim 1 , wherein the nucleic acid comprises the nucleotide sequence of SEQ ID NOs: 14, 16, 30, 32, 46, 48, 62, 64, 78, 80, 94, 96, 481, 483, 497, or 499.

3. A vector comprising the nucleic acid of claim 1 .

4. A host cell comprising the nucleic acid according to claim 1 .

5. A process for producing an antibody or antigen binding fragment comprising cultivating the host cell of claim 4 and recovering the antibody from cell culture.

6. The process of claim 5 wherein recovering the antibody from cell culture comprises the steps of:
a) removing cells and filtering the culture;
b) purifying the culture by affinity chromatography;
c) inactivating any viruses in the culture by adjusting the pH to 3.4-3.6, then readjusting the pH to 5.8-6.2 and filtering the culture;
d) purifying the culture by cation exchange chromatography and performing on-column reduction of the culture;
e) performing anion exchange chromatography on the culture;
f) removing viruses by nanofiltration;
g) filtering the culture containing the antibody; and
h) obtaining purified antibody.

7. A process for producing an anti-CCR7 antibody drug conjugate comprising:
(a) pre-forming a linker-drug moiety of the following Formula:

wherein:
the drug moiety is DM1, DM3 or DM4 and the drug moiety is attached to the linker via its thiol functionality;
L 1 is a C 1-6 alkylene wherein one of the methylene groups may be replaced with oxygen;
L 2 is a C 1-6 alkylene or is —(CH 2 CH 2 O) y —CH 2 —CH 2 — wherein y is 1 to 11;
X is —C(O)—NH—, —NHC(O)— or a triazole; and alkylene is linear or branched;
(b) conjugating said linker-drug moiety to the antibody recovered from the cell culture of claim 6 to produce an antibody drug conjugate; and
(c) purifying the antibody drug conjugate.

8. The process according to claim 7 comprising:
(a) pre-forming a linker-drug moiety of the following Formula:

 and
(b) conjugating said linker-drug moiety to the antibody recovered from the cell culture of claim 6 to produce an antibody drug conjugate; and
(c) purifying the antibody drug conjugate.

9. A process for producing an anti-CCR7 antibody drug conjugate comprising:
(a) pre-forming a linker-drug moiety of the following Formula:

wherein:
the drug moiety is DM1, DM3 or DM4 and the drug moiety is attached to the linker via its thiol functionality;
L 1 is a C 1-6 alkylene wherein one of the methylene groups may be replaced with oxygen;
L 2 is a C 1-6 alkylene or is —(CH 2 CH 2 O) y —CH 2 —CH 2 — wherein y is 1 to 11;
X is —C(O)—NH—, —NHC(O)— or a triazole; and alkylene is linear or branched;
(b) conjugating said linker-drug moiety to an antibody or antigen binding fragm

Assignees

• Novartis Ag

Inventors

• Bender Steven
• Charlton Tracy
• Galkin Anna
• Geierstanger Bernhard Hubert
• Glaser Scott Martin
• Kasibhatla Shailaja
• Knuth Mark
• Rottmann Sabine
• Rue Sarah
• Spraggon Glen
• Uno Tetsuo

Classifications

• A61K47/68033

  the drug being a maytansine · CPC title

• A61K47/68031

  the drug being an auristatin · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title