# US 10,501,541 B2 · Single domain antibodies targeting CD1d

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- Number: US 10,501,541 B2
- Document ID: US10501541B2
- Status: Granted
- Kind: B2
- Application number: 15/546,406
- Filed: 2016-01-27
- Published: 2018-05-24
- Granted: 2019-12-10
- Earliest claimed: 2015-01-27
- Assignees: Lava Therapeutics N.V.
- Applicants: Lava Therapeutics B.V.
- Inventors: Johannes Jelle Van Der Vliet; Tanja Denise De Gruijl; Hendrik Marinus Willem Verheul; Renée Cornelia Gerarda De Bruin; Roeland Lameris
- Web page: https://patentgrep.com/patent/US10501541B2

## CPC

- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/06: Antiasthmatics
- A61P 17/06: Antipsoriatics
- A61P 21/04: for myasthenia gravis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/04: Immunostimulants
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- C07K 16/30: from tumour cells
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/75: Agonist effect on antigen
- 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)

## Abstract

The invention relates to compounds, in particular polypeptides that specifically bind to the non-classical MHC protein CD1d and modulate CD1d-mediated biological functions. The invention in particular relates to such compounds and polypeptides comprising or consisting of at least one single domain antibody, and wherein at least one single domain antibody specifically binds to CD1d. Also provided is for methods and use employing such compounds, polypeptides and/or single-domain antibodies.

## Claims

### Claim 1

A compound comprising at least one single-domain antibody which binds to human CD1d, wherein the single-domain antibody comprises complementarity determining regions CDR1, CDR2 and CDR3, wherein CDR1 comprises the amino acid sequence set forth in SEQ ID NO:33, CDR2 comprises the amino acid sequence set forth in SEQ ID NO:54 and CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75.

### Claim 2 (depends on 1)

A compound according to claim 1, wherein the compound comprises the amino acid sequence set forth in SEQ ID NO:12, or a conservative sequence variant thereof.

### Claim 3 (depends on 1)

A compound according to claim 1, wherein the compound comprises a label, wherein an pharmaceutical active agent is linked to the compound, wherein the compound is a bivalent or multivalent compound, wherein the compound is fused to an antigen, a peptide or a nucleotide sequence, wherein the compound is a liposome, wherein the compound is a virus, and/or wherein the compound is a nanoparticle.

### Claim 4 (depends on 1)

A compound according to claim 1, wherein the compound binds to human CD1d but not to human CD1a, human CD1b and/or human CD1c.

### Claim 5 (depends on 1)

A compound according to claim 1, wherein
the compound is capable of inducing activation of CD1d-restricted T cells, including invariant natural killer T-cells, and/or stimulating alpha-galactosyl ceramide, induced activation of CD1d-restricted T cells, including invariant natural killer T-cells.

### Claim 6 (depends on 1)

A compound according to claim 1, wherein the compound is a single domain antibody.

### Claim 7 (depends on 1)

A compound according to claim 1, wherein the single domain antibody is a humanized single domain antibody.

### Claim 8 (depends on 1)

A compound according to claim 1, for use in medical treatment, or for in vivo use as a diagnostic agent.

### Claim 9 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1.

### Claim 10 (depends on 1)

A nucleotide sequence that encodes a compound according to claim 1.

### Claim 11 (depends on 1)

An isolated host cell or non-human organism comprising a nucleotide sequence encoding a compound according to claim 1.

### Claim 12 (depends on 11)

The host cell according to claim 11 that produces said compound or part thereof.

### Claim 13 (depends on 12)

A method for preparing a compound comprising at least one single-domain antibody which binds to human CD1d, wherein the method comprises culturing the host cell of claim 12 to express the compound or part thereof; and obtaining the compound.

### Claim 14

An antibody that comprises a CDR1, CDR2 and CDR3, wherein the CDR1 has the amino acid sequence set forth in SEQ ID NO:33, the CDR2 has the amino acid sequence set forth in SEQ ID NO:54 and CDR3 has the amino acid sequence set forth in SEQ ID NO:75.

### Claim 15 (depends on 1)

A compound according to claim 1, wherein the compound comprises the amino acid sequence set forth in SEQ ID NO: 12.

### Claim 16 (depends on 1)

A compound according to claim 1, wherein the compound further comprises an additional single domain antibody.

### Claim 17 (depends on 1)

A compound according claim 1, wherein the compound is a bispecific or multispecific compound.

### Claim 18 (depends on 1)

A compound according claim 1, wherein the compound is linked to another antibody.
