# US 11,999,793 B2 · Therapeutic anti-CD9 antibody

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- Number: US 11,999,793 B2
- Document ID: US11999793B2
- Status: Granted
- Kind: B2
- Application number: 17/476,650
- Filed: 2021-09-16
- Published: 2022-03-03
- Granted: 2024-06-04
- Earliest claimed: 2016-01-08
- Assignees: Kling Biotherapeutics B.V.
- Applicants: Kling Biotherapeutics B.V.
- Inventors: Hergen Spits; Paula Maria Wilhelmina Van Helden; Remko Schotte; Wouter Pos; Christien Fatmawati; Danïel Michiel Go; Koen Wagner; Julien Christian Villaudy
- Web page: https://patentgrep.com/patent/US11999793B2

## CPC

- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61P 35/00: Antineoplastic agents
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C07K 16/2818: {against CD28 or CD152}
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/21: from primates, e.g. man
- 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 2317/54: F(ab')2
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- G01N 2333/70596: Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
- 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)
- 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)
- 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)

## Abstract

The present invention provides novel binding compounds and therapeutic applications thereof.

## Claims

### Claim 1

A method for at least in part treating a disorder associated with CD9-expressing cells, comprising administering to an individual in need thereof a therapeutically effective amount of an antibody or functional part or functional equivalent that comprises:
a heavy chain CDR1 sequence that has at least 80% sequence identity with the sequence DYAMH (SEQ ID NO:2), and
a heavy chain CDR2 sequence that has the sequence GISWNSGSIVYADSVKG (SEQ ID NO:4), and
a heavy chain CDR3 sequence that has at least 80% sequence identity with the sequence AVSGYYPYFDY (SEQ ID NO:6), and
a light chain CDR1 sequence that has the sequence KSSQSVLYSSNNKNYLG (SEQ ID NO:8), and
a light chain CDR2 sequence that has at least 80% sequence identity with the sequence WASTRES (SEQ ID NO:10), and
a light chain CDR3 sequence that has the sequence QQYYTTP (SEQ ID NO:12);
or administering to said individual a nucleic acid molecule or functional equivalent encoding said antibody or functional part or functional equivalent, or a vector comprising said nucleic acid molecule or functional equivalent, or an isolated or recombinant cell comprising said nucleic acid molecule or functional equivalent, or a composition comprising said antibody or functional part or functional equivalent, or a composition comprising said nucleic acid molecule or functional equivalent, or a composition comprising said vector or said cell.

### Claim 2 (depends on 1)

The method according to claim 1 wherein said disorder is selected from the group consisting of a CD9 positive cancer, osteoporosis, arthritis, lung inflammation, COPD, colitis, a virus infection, a bacterial infection, CMV retinitis, oral candidiasis, Glanzmann thrombasthenia, diphtheria, and a disorder associated with innate lymphoid cells.

### Claim 3 (depends on 2)

The method according to claim 2, wherein said CD9 positive cancer is selected from the group consisting of melanoma, colorectal cancer, pancreatic cancer, esophageal cancer, lung cancer, breast cancer, ovarian cancer, stomach cancer, squamous cell carcinoma, AML, multiple myeloma, gastric cancer, liver cancer, brain cancer, Kaposi sarcoma, carcinoma mucoepidermoid, choriocarcinoma, fibrosarcoma, cervical carcinoma, glioma, adenocarcinoma, lung adenocarcinoma, non-small-cell lung carcinoma, bladder cancer and small cell lung cancer.

### Claim 4 (depends on 1)

The method according to claim 1, whereby said antibody or functional part or functional equivalent or nucleic acid molecule or functional equivalent or vector or cell is combined with a therapeutic agent useful in the treatment of a disorder associated with CD9-expressing cells.

### Claim 5 (depends on 4)

The method according to claim 4, wherein said therapeutic agent is useful in the treatment of a CD9 positive cancer.

### Claim 6 (depends on 4)

The method according to claim 4 wherein said agent is a complement regulatory protein or an agent capable of stimulating C3 convertase formation or capable of counteracting inhibition of C3 convertase formation or a CD55 blocking antibody or a CD46 blocking antibody or a CD59 blocking antibody or an antibody against another complement regulatory protein, the blocking of which enhances complement dependent cytotoxicity, or a blocking antibody specific for a co-inhibitory T cell molecule, or a small molecule against mutated BRAF, or another chemotherapy agent.

### Claim 7 (depends on 6)

The method according to claim 6, wherein said blocking antibody specific for a co-inhibitory T cell molecule is a PD-1 blocking antibody or a PD-L1 blocking antibody.

### Claim 8 (depends on 6)

The method according to claim 6 wherein said blocking antibody specific for a co-inhibitory T cell molecule is selected from the group consisting of an anti-CTLA4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-PD-L2 antibody, an anti-SIRPα antibody, an anti-TIM3 antibody, an anti-LAG3 antibody, an anti-CD276 antibody, an anti-CD272 antibody, an anti-KIR antibody, an anti-A2AR antibody, an anti-VISTA antibody and an anti-IDO antibody.

### Claim 9 (depends on 1)

The method according to claim 1, wherein said antibody or functional part or functional equivalent is specific for an epitope of CD9 comprising at least one amino acid selected from the group consisting of K169, D171, V172 and L173 of the CD9 sequence as depicted in SEQ ID NO:19.

### Claim 10 (depends on 1)

The method according to claim 1, wherein said antibody or functional part or functional equivalent is specific for an epitope of CD9 comprising amino acids corresponding to K169, D171, V172, L173 and F176 of the CD9 sequence as depicted in SEQ ID NO:19.

### Claim 11 (depends on 1)

The method according to claim 1, wherein said antibody or functional part or functional equivalent comprises:
a heavy chain CDR1 sequence DYAMH (SEQ ID NO:2) or DYAMY (SEQ ID NO:21); and
a heavy chain CDR2 sequence GISWNSGSIVYADSVKG (SEQ ID NO:4); and
a heavy chain CDR3 sequence AVSGYYPYFDY (SEQ ID NO:6) or AVSGYFPYFDY (SEQ ID NO:22) or AVSGYYPYFHY (SEQ ID NO:23) or AVSGYFPYFHY (SEQ ID NO:24); and
a light chain CDR1 sequence KSSQSVLYSSNNKNYLG (SEQ ID NO:8); and
a light chain CDR2 sequence WASTRES (SEQ ID NO:10) or WASIRES (SEQ ID NO:25); and
a light chain CDR3 sequence QQYYTTP (SEQ ID NO:12).

### Claim 12 (depends on 1)

The method according to claim 1, wherein said antibody or functional part or functional equivalent comprises a heavy chain variable region sequence having at least 90% sequence identity with the sequence
(SEQ ID NO: 14)
EVQVVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYYPYFDYWGQGILVTVSS.

### Claim 13 (depends on 1)

The method according to claim 1, wherein said antibody or functional part or functional equivalent comprises a light chain variable region sequence having at least 90% sequence identity with the sequence
(SEQ ID NO: 16)
DIVMTQSPDSLSVSLGERATINCKSSQSVLYSSNNKNYLGWYQQKPGQPP
KLHYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTP
STFGQGTRLEIK.

### Claim 14 (depends on 1)

The method according to claim 1, wherein said antibody or functional part or functional equivalent comprises:
a heavy chain variable region sequence
(SEQ ID NO: 14)
EVQVVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYYPYFDYWGQGILVTVSS,
or
(SEQ ID NO: 26)
EVQVVESGGGLVQPGRSLRLSCAASGFTFDDYAMYWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYEAKAV
SGYFPYFDYWGQGILVTVSS
or
(SEQ ID NO: 27)
EVQVVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYFPYFDYWGQGILVTVSS
or
(SEQ ID NO: 28)
EVQVVESGGGLVQPGRSLRLSCAASGFTEDDYAMHWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYFPYFHYWGQGILVTVSS
or
(SEQ ID NO: 31)
EVQVVESGGGLVQPGRSLRLSCAASGFTFDDYAMYWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYFPYFHYWGQGILVTVSS
or
(SEQ ID NO: 90)
EVQVVESGGGLVQPGRSLRLSCAASGFNEDDYAMYWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYFPYFHYWGQGILVTVSS
or
(SEQ ID NO: 84)
EVQVVESGGGLVQPGRSLRLSCAASGFTFDDYAMYWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYYPYFDYWGQGILVTVSS
or
(SEQ ID NO: 87)
EVQVVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYYPYFHYWGQGILVTVSS
or
(SEQ ID NO: 88)
EVQVVESGGGLVQPGRSLRLSCAASGFNFDDYAMHWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYYPYFDYWGQGILVTVSS
or
(SEQ ID NO: 89)
EVQVVESGGGLVQPGRSLRLSCAASGFNFDDYAMHWVRQAPGKGLEWVSG
ISWNSGSIVYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAFYYCAKAV
SGYYPYFHYWGQGILVTVSS
and/or
a light chain variable region sequence
(SEQ ID NO: 16)
DIVMTQSPDSLSVSLGERATINCKSSQSVLYSSNNKNYLGWYQQKPGQPP
KLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTT
PSTFGQGTRLEIK
or
(SEQ ID NO: 32)
DIVMTQSPDSLSVSLGERATINCKSSQSSVLYSSNNKNYLGWYQQKPGQP
PKLLIYWASIRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYT
TPSTFGQGTRLEIK.

### Claim 15 (depends on 1)

The method according to claim 1, wherein said antibody or functional part or functional equivalent is coupled to another compound.

### Claim 16 (depends on 15)

The method according to claim 15, wherein said other compound is a detectable label, a chemotherapeutic drug, a toxic moiety, an immunomodulatory molecule, another CD9-specific binding compound, a CD3-specific binding compound, or a radioactive compound.