# US 11,306,153 B2 · Anti-AXL tyrosine kinase receptor antibodies and uses thereof

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- Number: US 11,306,153 B2
- Document ID: US11306153B2
- Status: Granted
- Kind: B2
- Application number: 16/303,657
- Filed: 2017-05-22
- Published: 2020-10-08
- Granted: 2022-04-19
- Earliest claimed: 2016-05-20
- Assignees: Agency for Science, Technology and Research
- Applicants: Agency for Science, Technology and Research
- Inventors: Mei Yee Vanessa Ding; Boon Hwa Andre Choo; Wey Jia Fong
- Web page: https://patentgrep.com/patent/US11306153B2

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/40: against enzymes
- A61K 47/6825: {Ribosomal inhibitory proteins, i.e. RIP-I or RIP-II, e.g. Pap, gelonin or dianthin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61P 35/00: Antineoplastic agents
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- G01N 33/57515: of the breast
- G01N 33/5752: of the lungs
- G01N 33/57525: of the liver or pancreas
- G01N 33/57545: of the ovaries
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- 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 2317/31: multispecific
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/626: Diabody or triabody
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/77: Internalization into the cell
- C07K 2319/00: Fusion polypeptide
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to antigen-binding proteins, or antigen-binding fragments thereof that bind to a glycan on the AXL receptor tyrosine kinase. The present invention also relates to antigen-binding proteins, or antigen-binding fragment conjugated to a radioisotope or cytotoxin, and wherein said antigen-binding proteins, or antigen-binding fragment is internalised into a cell upon binding to AXL receptor tyrosine kinase. Compositions comprising a physiologically acceptable carrier and a therapeutically effective amount of the antigen-binding protein, or antigen-binding fragment thereof, therapeutic use of the antigen-binding protein, or antigen-binding fragment thereof, methods for detecting cancer as well as kits when used in such methods are also provided.

## Claims

### Claim 1

An antigen-binding protein, or an antigen-binding fragment thereof, that binds to AXL receptor tyrosine kinase, comprising (i) a heavy chain variable domain (VH) comprising a VH complementarity determining region (CDR) 1 (VHCDR1) having the amino acid sequence GFTFTSYYMY (SEQ ID NO: 3), a VHCDR2 having the amino acid sequence GVSPSNGGANFNEKFKT (SEQ ID NO: 4), and a VHCDR3 having the amino acid sequence FLYGPRYFDV (SEQ ID NO: 5); and (ii) a light chain variable domain (VL) comprising a VL complementarity determining region (CDR) 1 (VLCDR1) having the amino acid sequence RASESVDNYGISFMN (SEQ ID NO: 6), a VLCDR2 having the amino acid sequence QQSKEVPYT (SEQ ID NO: 7), and a VLCDR3 having the amino acid sequence (SEQ ID NO: 8).

### Claim 2 (depends on 1)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 1, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:1.

### Claim 3 (depends on 1)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 1, wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:2.

### Claim 4 (depends on 1)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 1, wherein the antigen binding protein is selected from the group consisting of monoclonal, recombinant, polyclonal, chimeric, humanized, bispecific, and heteroconjugate antibodies; and wherein the antigen-binding fragment thereof is selected from the group consisting of a domain antibody, antigen binding fragments, single chain Fv, a single chain antibody, a univalent antibody lacking a hinge region, a minibody, a diabody, and a tandem diabody; optionally wherein the antigen-binding protein is a monoclonal antibody; optionally wherein the monoclonal antibody is humanized.

### Claim 5 (depends on 1)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 1, wherein the antigen-binding protein, or antigen-binding fragment thereof, binds to a glycan on the AXL receptor tyrosine kinase; optionally wherein the glycan is an O-linked glycan.

### Claim 6 (depends on 1)

The antigen-binding protein, or an antigen-binding fragment thereof, as claimed in claim 1, comprising a radioisotope or a cytotoxin conjugated thereto; optionally wherein the antigen-binding protein, or antigen-binding fragment, comprising a radioisotope or cytotoxin conjugated thereto is internalized into a cell upon binding to AXL receptor tyrosine kinase.

### Claim 7 (depends on 6)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 6, wherein the antigen-binding protein, or antigen-binding fragment thereof, is conjugated with a cytotoxin selected from the group consisting of monomethyl auristatin E (MMAE-1), mertansine (DM-1) and saporin.

### Claim 8 (depends on 1)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 1, wherein the antigen-binding protein, or antigen-binding fragment thereof, is formulated as a composition comprising a physiologically acceptable carrier.

### Claim 9 (depends on 8)

The antigen-binding protein, or antigen-binding fragment thereof as claimed in claim 8, wherein the composition comprises a further active pharmaceutical ingredient selected from the group consisting of bevacizumab, carboplatin, paclitaxel, and gefitinib.

### Claim 10 (depends on 1)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98% or about 99% identical to the heavy chain variable region set forth in SEQ ID NO: 1.

### Claim 11 (depends on 1)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 1, wherein the light chain variable region comprises an amino acid sequence that is about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98% or about 99% identity to the amino acid sequence set forth in SEQ ID NO:2.

### Claim 12 (depends on 4)

The antigen-binding protein, or antigen-binding fragment thereof, as claimed in claim 4, wherein the antigen binding protein, or antigen binding fragment thereof, is a humanized monoclonal antibody.

### Claim 13

An antibody that comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2.

### Claim 14

A method of treating an AXL-expressing cancer comprising administering an antigen-binding protein, or an antigen-binding fragment thereof, that binds to AXL receptor tyrosine kinase, to a subject in need thereof, wherein the antigen-binding protein, or the antigen-binding fragment thereof, comprises (i) a heavy chain variable domain (VH) comprising a VH complementarity determining region (CDR) 1 (VHCDR1) having the amino acid sequence GFTFTSYYMY (SEQ ID NO: 3); a VHCDR2 having the amino acid sequence GVSPSNGGANFNEKFKT (SEQ ID NO: 4), and a VHCDR3 having the amino acid sequence FLYGPRYFDV (SEQ ID NO: 5); and (ii) a light chain variable domain (VL) comprising a VL complementarity determining region (CDR) 1 (VLCDR1) having the amino acid sequence RASESVDNYGISFMN (SEQ ID NO: 6), a VLCDR2 having the amino acid sequence GASNQGS (SEQ ID NO: 7), and a VLCDR3 having the amino acid sequence QQSKEVPYT (SEQ ID NO: 8), to thereby treat the AXL-expressing cancer.

### Claim 15 (depends on 14)

The method of claim 14, wherein the cancer is selected from the group consisting of triple-negative breast cancer, non-small cell lung cancer, ovarian cancer, kidney cancer, and pancreatic cancer.

### Claim 16 (depends on 14)

The method of claim 14, wherein the antigen-binding protein, or the antigen-binding fragment thereof, is conjugated with a radioisotope or a cytotoxin.

### Claim 17 (depends on 14)

The method of claim 14, wherein the method comprises administering a further active pharmaceutical ingredient to the subject; optionally wherein the further pharmaceutical agent is administered separately, simultaneously or sequentially.

### Claim 18 (depends on 14)

The method of claim 14, wherein the antigen-binding protein, or an antigen-binding fragment thereof, is administered with chemotherapy; optionally wherein the chemotherapy is administered separately, simultaneously or sequentially.