# US 9,433,687 B2 · Anti-Notch3 antibodies and antibody-drug conjugates

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- Number: US 9,433,687 B2
- Document ID: US9433687B2
- Status: Granted
- Kind: B2
- Application number: 14/073,273
- Filed: 2013-11-06
- Published: 2014-05-08
- Granted: 2016-09-06
- Earliest claimed: 2012-11-07
- Assignees: Pfizer Inc.
- Applicants: Pfizer Inc.
- Inventors: Kenneth G. Geles; Yijie Gao; Puja Sapra; Lioudmila Gennadievna Tchistiakova; Bin-Bing Stephen Zhou
- Web page: https://patentgrep.com/patent/US9433687B2

## CPC

- C07K 16/3061: {Blood cells}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 47/6817: {Toxins}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6855: {the tumour determinant being from breast cancer cell}
- A61K 47/6857: {the tumour determinant being from lung cancer cell}
- A61K 47/6863: {the tumour determinant being from stomach or intestines cancer cell}
- A61K 47/6867: {the tumour determinant being from a cell of a blood cancer}
- A61K 47/6869: {the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate}
- A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/3015: {Breast}
- C07K 16/3023: {Lung}
- C07K 16/3046: {Stomach, Intestines}
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07K 16/32: against translation products of oncogenes
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 2039/505: {comprising antibodies}
- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- C07K 16/30: from tumour cells
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/66: comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/75: Agonist effect on antigen
- 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 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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

The present invention provides for anti-Notch3 antibodies, anti-Notch3 antibody-drug conjugates and methods for preparing and using the same.

## Claims

### Claim 1

An isolated antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising:
a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 13; and
a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 25.

### Claim 2 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody or antigen-binding fragment:
(a) internalizes into a cell,
(b) does not inhibit Notch3 signaling, or
(c) does not activate Notch3 signaling.

### Claim 3 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody or antigen-binding fragment:
(a) binds to the Lin 12/Notch repeat (LNR)-C and heterodimerization (HD)-1 domains of the Notch3 Negative Regulatory Region (NRR),
(b) does not maintain the Notch3 NRR in an auto-inhibitory conformation, or
(c) does not inhibit S2-cleavage.

### Claim 4 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, comprising:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15 or 16; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 19 or 20; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 23; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 27; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 29; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 31.

### Claim 5 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, comprising a heavy chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 13 or a light chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 25.

### Claim 6 (depends on 5)

The isolated antibody, or antigen-binding fragment thereof, of claim 5, comprising a heavy chain variable region amino acid sequence of SEQ ID NO: 13.

### Claim 7 (depends on 6)

The isolated antibody, or antigen-binding fragment thereof, of claim 6, comprising a heavy chain amino acid sequence of SEQ ID NO: 33.

### Claim 8 (depends on 5)

The isolated antibody, or antigen-binding fragment thereof, of claim 5, comprising a light chain variable region amino acid sequence of SEQ ID NO: 25.

### Claim 9 (depends on 8)

The isolated antibody, or antigen-binding fragment thereof, of claim 8, comprising a light chain amino acid sequence of SEQ ID NO: 35.

### Claim 10 (depends on 1)

An antibody-drug conjugate comprising a cytotoxic agent conjugated to the antibody, or antigen-binding fragment thereof, of claim 1.

### Claim 11 (depends on 10)

A pharmaceutical composition comprising the antibody-drug conjugate of claim 10 and a pharmaceutically acceptable carrier.

### Claim 12 (depends on 1)

A composition comprising the antibody of claim 1.

### Claim 13

An isolated antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising:
a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 37; and
a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 49.

### Claim 14 (depends on 13)

An isolated antibody, or antigen-binding fragment thereof, of claim 13, comprising:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 39 or 40; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 43 or 44; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 47; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 51; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 53; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 55.

### Claim 15 (depends on 13)

The isolated antibody, or antigen-binding fragment thereof, of claim 13, comprising a heavy chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 37 or a light chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 49.

### Claim 16 (depends on 15)

The isolated antibody, or antigen-binding fragment thereof, of claim 15, comprising a heavy chain variable region amino acid sequence of SEQ ID NO: 37.

### Claim 17 (depends on 16)

The isolated antibody, or antigen-binding fragment thereof, of claim 16, comprising a heavy chain amino acid sequence of SEQ ID NO: 57.

### Claim 18 (depends on 15)

The isolated antibody, or antigen-binding fragment thereof, of claim 15, comprising a light chain variable region amino acid sequence of SEQ ID NO: 49.

### Claim 19 (depends on 18)

The isolated antibody, or antigen-binding fragment thereof, of claim 18, comprising a light chain amino acid sequence of SEQ ID NO: 59.

### Claim 20 (depends on 13)

An antibody-drug conjugate comprising a cytotoxic agent conjugated to the antibody, or antigen-binding fragment thereof, of claim 13.

### Claim 21 (depends on 20)

A pharmaceutical composition comprising the antibody-drug conjugate of claim 20 and a pharmaceutically acceptable carrier.

### Claim 22 (depends on 13)

A composition comprising the antibody of claim 13.

### Claim 23

An antibody-drug conjugate of the formula:
Ab-(L-D)p,
wherein:
(a) Ab is an antibody, or antigen-binding fragment thereof, that binds to Notch3;
(b) L-D is a linker-drug moiety, wherein L is a linker selected from the group consisting of maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (vc), maleimidocaproyl (mc), maleimido-heptanoyl (me) and maleimido-Peg6C2 (MalPeg6C2) and D is a drug selected from the group consisting of:
(i) 0101 having the formula:
(ii) 6780 having the formula:
(iii) 0131 having the formula:
(iv) 3377 having the formula:
and
(v) 8261 having the formula:
and
(c) p is an integer from 1 to 12.

### Claim 24 (depends on 23)

A pharmaceutical composition comprising the antibody-drug conjugate of claim 23 and a pharmaceutically acceptable carrier.

### Claim 25 (depends on 23)

The antibody-drug conjugate of claim 23, wherein Ab comprises:
a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 13; and a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 25; or
a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 49.

### Claim 26 (depends on 23)

The antibody-drug conjugate of claim 23, wherein Ab comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15 or 16; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 19 or 20; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 23; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 27; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 29; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 31; or
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 39 or 40; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 43 or 44; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 47; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 51; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 53; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 55.

### Claim 27 (depends on 26)

The antibody-drug conjugate of claim 26, wherein Ab comprises:
a heavy chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 13 or a light chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 25; or
a heavy chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 37 or a light chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 49.

### Claim 28 (depends on 27)

The antibody-drug conjugate of claim 27, wherein Ab comprises a heavy chain variable region amino acid sequence of SEQ ID NO: 13; or a heavy chain variable region amino acid sequence of SEQ ID NO: 37.

### Claim 29 (depends on 28)

The antibody-drug conjugate of claim 28, wherein Ab comprises a heavy chain amino acid sequence of SEQ ID NO: 33; or a heavy chain amino acid sequence of SEQ ID NO: 57.

### Claim 30 (depends on 27)

The antibody-drug conjugate of claim 27, wherein Ab comprises a light chain variable region amino acid sequence of SEQ ID NO: 25 or a light chain variable region amino acid sequence of SEQ ID NO: 49.

### Claim 31 (depends on 30)

The antibody-drug conjugate of claim 30, wherein Ab comprises a light chain amino acid sequence of SEQ ID NO: 35; or a light chain amino acid sequence of SEQ ID NO: 59.

### Claim 32

An antibody-drug conjugate of the formula:
Ab-(L-D)p,
wherein:
(a) Ab is an antibody, or antigen-binding fragment thereof, that binds to Notch3,
(b) L-D is a linker-drug moiety, wherein L is a linker and D is a drug, wherein L-D is selected from the group consisting of:
vc0101 having the formula:
and vc6780 having the formula:
and
(c) p is an integer from 1 to 12.

### Claim 33 (depends on 32)

A pharmaceutical composition comprising the antibody-drug conjugate of claim 32 and a pharmaceutically acceptable carrier.

### Claim 34 (depends on 32)

The antibody-drug conjugate of claim 32, wherein Ab comprises:
a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 13; and a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 25; or
a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 49.

### Claim 35 (depends on 32)

The antibody-drug conjugate of claim 32, wherein Ab comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15 or 16; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 19 or 20; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 23; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 27; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 29; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 31; or
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 39 or 40; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 43 or 44; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 47; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 51; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 53; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 55.

### Claim 36 (depends on 35)

The antibody-drug conjugate of claim 35, wherein Ab comprises:
a heavy chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 13 or a light chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 25; or
a heavy chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 37 or a light chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 49.

### Claim 37 (depends on 36)

The antibody-drug conjugate of claim 36, wherein Ab comprises a heavy chain variable region amino acid sequence of SEQ ID NO: 13; or a heavy chain variable region amino acid sequence of SEQ ID NO: 37.

### Claim 38 (depends on 37)

The antibody-drug conjugate of claim 37, wherein Ab comprises a heavy chain amino acid sequence of SEQ ID NO: 33; or a heavy chain amino acid sequence of SEQ ID NO: 57.

### Claim 39 (depends on 36)

The antibody-drug conjugate of claim 36, wherein Ab comprises a light chain variable region amino acid sequence of SEQ ID NO: 25 or a light chain variable region amino acid sequence of SEQ ID NO: 49.

### Claim 40 (depends on 39)

The antibody-drug conjugate of claim 39, wherein Ab comprises a light chain amino acid sequence of SEQ ID NO: 35; or a light chain amino acid sequence of SEQ ID NO: 59.

### Claim 41

An antibody-drug conjugate of the formula:
Ab-(L-D)p,
wherein:
(a) Ab is an antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising a VH CDR1, a VH CDR2 and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 13 and a VL CDR1, a VL CDR2 and VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 25;
(b) L-D is a linker-drug moiety, wherein L is a linker, and D is a drug; and
(c) p is an integer from 1 to 12.

### Claim 42 (depends on 41)

The antibody-drug conjugate of claim 41, wherein L is selected from the group consisting of maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (vc), maleimidocaproyl (mc), maleimido-heptanoyl (me) and maleimido-Peg6C2 (MalPeg6C2).

### Claim 43 (depends on 42)

The antibody-drug conjugate of claim 42, wherein D is selected from the group consisting of:
(a) 0101 having the formula:
(b) 6780 having the formula:
(c) 0131 having the formula:
(d) 3377 having the formula:
and
(e) 8261 having the formula:

### Claim 44 (depends on 41)

The antibody-drug conjugate of claim 41, wherein L-D is selected from the group consisting of:
vc0101 having the formula:
and vc6780 having the formula:

### Claim 45 (depends on 41)

A pharmaceutical composition comprising the antibody-drug conjugate of claim 41 and a pharmaceutically acceptable carrier.

### Claim 46 (depends on 41)

The antibody-drug conjugate of claim 41, wherein Ab comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15 or 16; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 19 or 20; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 23; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 27; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 29; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 31.

### Claim 47 (depends on 41)

The antibody-drug conjugate of claim 41, wherein Ab comprises a heavy chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 13 or a light chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 25.

### Claim 48 (depends on 47)

The antibody-drug conjugate of claim 47, wherein Ab comprises a heavy chain variable region amino acid sequence of SEQ ID NO: 13.

### Claim 49 (depends on 48)

The antibody-drug conjugate of claim 48, wherein Ab comprises a heavy chain amino acid sequence of SEQ ID NO: 33.

### Claim 50 (depends on 47)

The antibody-drug conjugate of claim 47, wherein Ab comprises a light chain variable region amino acid sequence of SEQ ID NO: 25.

### Claim 51 (depends on 50)

The antibody-drug conjugate of claim 50, wherein Ab comprises a light chain amino acid sequence of SEQ ID NO: 35.

### Claim 52

An antibody-drug conjugate of the formula:
Ab-(L-D)p,
wherein:
(a) Ab is an antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 37; and a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 49;
(b) L-D is a linker-drug moiety, wherein L is a linker, and D is a drug; and
(c) p is an integer from 1 to 12.

### Claim 53 (depends on 52)

The antibody-drug conjugate of claim 52, wherein L is selected from the group consisting of maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (vc), maleimidocaproyl (mc), maleimido-heptanoyl (me) and maleimido-Peg6C2 (MalPeg6C2).

### Claim 54 (depends on 53)

The antibody-drug conjugate of claim 53, wherein D is selected from the group consisting of:
(a) 0101 having the formula:
(b) 6780 having the formula:
(c) 0131 having the formula:
(d) 3377 having the formula:
and
(e) 8261 having the formula:

### Claim 55 (depends on 52)

The antibody-drug conjugate of claim 52, wherein L-D is selected from the group consisting of:
vc0101 having the formula:
and vc6780 having the formula:

### Claim 56 (depends on 52)

The antibody-drug conjugate of claim 52, wherein Ab comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 39 or 40; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 43 or 44; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 47; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 51; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 53; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 55.

### Claim 57 (depends on 52)

The antibody-drug conjugate of claim 52, wherein Ab comprises a heavy chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 37 or a light chain variable region having an amino acid sequence that is at least 90% identical to SEQ ID NO: 49.

### Claim 58 (depends on 57)

The antibody-drug conjugate of claim 57, wherein Ab comprises a heavy chain variable region amino acid sequence of SEQ ID NO: 37.

### Claim 59 (depends on 58)

The antibody-drug conjugate of claim 58, wherein Ab comprises a heavy chain amino acid sequence of SEQ ID NO: 57.

### Claim 60 (depends on 57)

The antibody-drug conjugate of claim 57, wherein Ab comprises a light chain variable region amino acid sequence of SEQ ID NO: 49.

### Claim 61 (depends on 60)

The antibody-drug conjugate of claim 60, wherein Ab comprises a light chain amino acid sequence of SEQ ID NO: 59.

### Claim 62 (depends on 52)

A pharmaceutical composition comprising the antibody-drug conjugate of claim 52 and a pharmaceutically acceptable carrier.

### Claim 63

An antibody-drug conjugate of the formula:
Ab-(L-D)p,
wherein:
(a) Ab is an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region amino acid sequence of SEQ ID NO: 13 and a light chain variable region amino acid sequence of SEQ ID NO 25;
(b) L-D is a linker-drug moiety, wherein L is a linker, and D is a drug, wherein the L-D is vc0101 having the formula
and
(c) p is an integer from 1 to 12.

### Claim 64 (depends on 63)

A pharmaceutical composition comprising the antibody-drug conjugate of claim 63 and a pharmaceutically acceptable carrier.