Anti-CCR7 antibody drug conjugates

Patent metadata

Field	Value
Publication number	US-11634497-B2
Application number	US-201816482173-A
Country	US
Kind code	B2
Filing date	Feb 1, 2018
Priority date	Feb 3, 2017
Publication date	Apr 25, 2023
Grant date	Apr 25, 2023

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. An antibody or antigen binding fragment thereof 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 antibody or antigen binding fragment thereof of claim 1 comprising:
a. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:13, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:29;
b. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:45, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:61;
c. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:77, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:93; or
d. A heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:608, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:624.

3. The antibody or antigen binding fragment thereof of claim 1 comprising:
a. A heavy chain comprising the amino acid sequence of SEQ ID NO:15, and a light chain comprising the amino acid sequence of SEQ ID NO:31;
b. A heavy chain comprising the amino acid sequence of SEQ ID NO:47, and a light chain comprising the amino acid sequence of SEQ ID NO:63;
c. A heavy chain comprising the amino acid sequence of SEQ ID NO:79, and a light chain comprising the amino acid sequence of SEQ ID NO:95; or
d. A heavy chain comprising the amino acid sequence of SEQ ID NO:610, and a light chain comprising the amino acid sequence of SEQ ID NO:626.

4. An antibody drug conjugate comprising the formula
Ab-(L-(D) m ) n
or a pharmaceutically acceptable salt thereof; wherein
Ab is an antibody or antigen binding fragment thereof according to claim 1 ;
L is a linker;
D is a drug moiety;
m is an integer from 1 to 8; and
n is an integer from 1 to 12.

5. The antibody drug conjugate of claim 4 , wherein said m is 1.

6. The antibody drug conjugate of claim 4 , wherein said n is about 3 to about 4.

7. The antibody drug conjugate of claim 4 , wherein the linker is derived from a cross-linking reagent selected from the group consisting of N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP), N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB), N-succinimidyl-4-(2-pyridyldithio)-2-sulfo-butanoate (sulfo-SPDB), N-succinimidyl iodoacetate (SIA), N-succinimidyl(4-iodoacetyl)aminobenzoate (SIAB), maleimide PEG NHS, N-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC), N-sulfosuccinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (sulfo-SMCC), and 2,5-dioxopyrrolidin-1-yl 17-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5,8,11,14-tetraoxo-4,7,10,13-tetraazaheptadecan-l-oate (CX1-1).

8. The antibody drug conjugate of claim 4 , wherein said linker has the following Formula (IIA):

wherein * is linked to the thiol functionality on the antibody or antigen binding fragment thereof, and ** is linked to the thiol functionality of the drug moiety; and wherein:
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 — where

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

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title

• C07K2317/30

  characterized by aspects of specificity or valency · CPC title