# US 10,946,106 B2 · Tumor-specific payload delivery and immune activation using a human antibody targeting a highly specific tumor cell surface antigen

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- Number: US 10,946,106 B2
- Document ID: US10946106B2
- Status: Granted
- Kind: B2
- Application number: 15/779,490
- Filed: 2016-11-29
- Published: 2018-12-27
- Granted: 2021-03-16
- Earliest claimed: 2015-11-30
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Bin Liu; Scott Bidlingmaier; Yang Su
- Web page: https://patentgrep.com/patent/US10946106B2

## CPC

- A61K 47/6871: {the antibody targeting an enzyme}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/68035: {the drug being a pyrrolobenzodiazepine}
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61P 35/00: Antineoplastic agents
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/40: against enzymes
- C12N 9/16: acting on ester bonds (3.1)
- C12Y 301/03001: Alkaline phosphatase (3.1.3.1)
- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- A61K 35/00: Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K 2039/505: {comprising antibodies}
- A61K 2039/572: {cytotoxic response}
- C07K 2317/31: multispecific
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/72: Increased effector function due to an Fc-modification
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES
- 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

This invention provides antibodies directed against a highly specific and previously unrecognized marker for cancerous cells. In certain embodiments an isolated antibody or fragment thereof that specifically binds human placentally expressed ALPP and/or ALPPL2, but not ALPL and ALPI that are expressed outside the placenta is provided as well as immunoconjugates comprising such antibodies.

## Claims

### Claim 1

An isolated antibody that binds human placentally expressed ALPP and/or ALPPL2, but not ALPL and ALPI that are expressed outside the placenta wherein:
said antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), where:
said heavy chain variable region comprises a variable heavy M25FYIA antibody CDR1 comprising the amino acid sequence GFTFSSYA (residues 26-33 of SEQ ID NO:6), a variable heavy M25FYIA antibody CDR2 comprising the amino acid sequence ISYDGSNK (residues 51-58 of SEQ ID NO:6, and a variable heavy M25FYIA antibody CDR3 comprising the amino acid sequence AKEGDSSRWSYDL (residues 97-109 of SEQ ID NO:6); and
said light chain variable region comprises a variable light M25FYIA antibody CDR1 comprising the amino acid sequence SSDVGGYNY (residues 161-169 of SEQ ID NO:6), a variable light M25FYIA antibody CDR2 comprising the amino acid sequence DVT (residues 187-189 of SEQ ID NO:6), and a variable light M25FYIA antibody CDR3 consisting of the amino acid sequence SSYTIASTLVV (residues 226-236 of SEQ ID NO:6).

### Claim 2 (depends on 1)

The antibody of claim 1, wherein said antibody preferentially binds the cell surface form of ALPPL2 as compared to the shed form of ALPPL2.

### Claim 3 (depends on 1)

The antibody of claim 1, wherein:
said antibody binds a cell expressing ALPPL2 with an affinity of better than about 5 nM; and/or
said antibody binds a cell expressing ALPPL2 with an affinity of better than about 50 pM in its IgG1 form.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein:
said antibody comprises a heavy chain variable region (VH) of an M25FYIA antibody comprising the amino acid sequence QVQLQQSGGGLVKPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSN KYYADSVKGRFTISRDNSKNTLYLQMDSLRAEDTAVYYCAKEGDSSRWSYDLWGRGT LVTVSS (residues 1-120 of SEQ ID NO:6); and
said antibody comprises a light chain variable region (VL) of an M25FYIA antibody comprising the amino acid sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKVMIYDVTNRPSG VSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTIASTLVVFGGGTKLTVL (residues 136-246 of SEQ ID NO:6).

### Claim 5 (depends on 1)

The antibody of claim 1, wherein said antibody is selected from the group consisting of an intact immunoglobulin, an Fv, a Fab, a (Fab′)2, a (Fab′)3, an IgGΔCH2, and a single-chain antibody.

### Claim 6 (depends on 1)

An immunoconjugate comprising the antibody of claim 1 attached to an effector wherein said effector is selected from the group consisting of a second antibody, a detectable label, a cytotoxin or cytostatic agent, a liposome containing a drug, a radionuclide, a drug, a prodrug, an immune modulator, a viral particle, a cytokine, and a chelate.

### Claim 7 (depends on 6)

The immunoconjugate of claim 6, wherein said effector is a second antibody.

### Claim 8 (depends on 7)

The immunoconjugate of claim 7, wherein said second antibody is an antibody that binds to CD3.

### Claim 9 (depends on 6)

The immunoconjugate of claim 6, wherein:
said antibody comprises a heavy chain variable region (VH) of an M25FYIA antibody comprising the amino acid sequence QVQLQQSGGGLVKPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSN KYYADSVKGRFTISRDNSKNTLYLQMDSLRAEDTAVYYCAKEGDSSRWSYDLWGRGT LVTVSS (residues 1-120 of SEQ ID NO:6); and
said antibody comprises a light chain variable region (VL) of an M25FYIA antibody comprising the amino acid sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKVMIYDVTNRPSG VSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTIASTLVVFGGGTKLTVL (residues 136-246 of SEQ ID NO:6).

### Claim 10 (depends on 6)

The immunoconjugate of claim 6, wherein said antibody is an intact immunoglobulin.

### Claim 11 (depends on 1)

A pharmaceutical formulation said formulation comprising:
a pharmaceutically acceptable carrier and the antibody of claim 1.