# US 12,180,291 B2 · Anti-CCR7 antibody drug conjugates

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,180,291 B2
- Document ID: US12180291B2
- Status: Granted
- Kind: B2
- Application number: 18/164,519
- Filed: 2023-02-03
- Published: 2024-03-21
- Granted: 2024-12-31
- Earliest claimed: 2023-02-03
- Assignees: Novartis AG
- Applicants: Novartis AG
- Inventors: Steven Bender; Tracy Charlton; Anna Galkin; Bernhard Hubert Geierstanger; Scott Martin Glaser; Shailaja Kasibhatla; Mark Knuth; Sabine Rottmann; Sarah Rue; Glen Spraggon; Tetsuo Uno
- Web page: https://patentgrep.com/patent/US12180291B2

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61K 39/39525: {Purification}
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/68033: {the drug being a maytansine}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

A vector comprising the nucleic acid of claim 1.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 4)

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.

### Claim 6 (depends on 5)

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.

### Claim 7 (depends on 6)

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;
L1 is a C1-6alkylene wherein one of the methylene groups may be replaced with oxygen;
L2 is a C1-6alkylene or is —(CH2CH2O)y—CH2—CH2— 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.

### Claim 8 (depends on 6, 7)

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.

### Claim 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;
L1 is a C1-6alkylene wherein one of the methylene groups may be replaced with oxygen;
L2 is a C1-6alkylene or is —(CH2CH2O)y—CH2—CH2— 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 fragment thereof to produce an antibody drug conjugate; and
(c) purifying the antibody drug conjugate,
wherein the antibody or antigen binding fragment thereof comprises:
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.

### Claim 10

A process for producing an anti-CCR7 antibody drug conjugate comprising:
(a) pre-forming a linker-drug moiety of the following Formula:
(b) conjugating said linker-drug moiety to an antibody or antigen binding fragment thereof of to produce an antibody drug conjugate; and
(c) purifying the antibody drug conjugate,
wherein the antibody or antigen binding fragment thereof comprises:
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.

### Claim 11 (depends on 7)

The process according to claim 7, wherein the step of pre-forming said linker-drug moiety comprises:
a) Reacting a drug moiety via its thiol functionality with:
to form:
b) Reacting the formed
with:
to form the linker-drug moiety:
wherein:
L1 is a C1-6alkylene wherein one of the methylene groups may be replaced with oxygen;
L2 is a C1-6alkylene or is —(CH2CH2O)y—CH2—CH2— wherein y is 1 to 11; and
X is —C(O)—NH—, —NHC(O)— or a triazole;
wherein the alkylene is linear or branched; and
RG1 and RG2 are 2 reactive groups forming group X.

### Claim 12 (depends on 8)

The process according to claim 8, wherein the step of pre-forming said linker-drug moiety comprises:
c) Reacting the drug moiety via its thiol functionality with:
to form:
d) Reacting the formed
with:
to form the linker-drug moiety:

### Claim 13 (depends on 7)

The antibody drug conjugate made according to claim 7 having an average DAR, measured with a UV spectrophotometer, of about 3 to about 4.

### Claim 14

A process for producing an anti-CCR7 antibody drug conjugate comprising:
(a) chemically linking SMCC or MPET to a drug moiety DM-1 or DM-4 to form a linker-drug;
(b) conjugating said linker-drug to an antibody or antigen binding fragment thereof; and
(c) purifying the antibody drug conjugate,
wherein the antibody or antigen binding fragment thereof comprises:
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.

### Claim 15 (depends on 14)

The antibody drug conjugate made according to claim 14 having an average DAR, measured with a UV spectrophotometer, of about 3 to about 4.

### Claim 16

A diagnostic reagent comprising 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 1 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.

### Claim 17 (depends on 16)

The diagnostic reagent of claim 16, wherein the antibody or antigen binding fragment thereof is labeled with a radiolabel, a fluorophore, a chromophore, an imaging agent, or a metal ion.