# US 12,006,357 B2 · Transthyretin antibodies and uses thereof

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- Number: US 12,006,357 B2
- Document ID: US12006357B2
- Status: Granted
- Kind: B2
- Application number: 17/255,796
- Filed: 2019-06-26
- Published: 2021-07-29
- Granted: 2024-06-11
- Earliest claimed: 2018-06-26
- Assignees: Mor Research Applications Ltd.
- Applicants: Mor Research Applications Ltd.
- Inventors: Michael Fassler; Jacob George
- Web page: https://patentgrep.com/patent/US12006357B2

## CPC

- C07K 16/18: against material from animals or humans
- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 25/00: Drugs for disorders of the nervous system
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- G01N 33/78: Thyroid gland hormones {, e.g. T3, T4, TBH, TBG or their receptors}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/90: characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2800/2814: Dementia; Cognitive disorders
- 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 disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human transthyretin (TTR). The anti-TTR antibodies or antigen-binding fragments thereof are useful, for example, in detecting TTR and in treating TTR amyloidosis in a subject.

## Claims

### Claim 1

An antibody or antigen-binding fragment thereof capable of binding human transthyretin (TTR), wherein the antibody or antigen-binding fragment thereof comprises a complementary determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:1 (GYTFTSYY), a CDR H2 comprising the amino acid sequence of SEQ ID NO:2 (IYPGNVNT), a CDR H3 comprising the amino acid sequence of SEQ ID NO:3 (ARTYFDY), a CDR L1 comprising the amino acid sequence of SEQ ID NO:4 (SSVSY), a CDR L2 comprising the amino acid sequence of SEQ ID NO:5 (DTS), and a CDR3 L3 comprising the amino acid sequence of SEQ ID NO:6 (QQWSSKSFT).

### Claim 2 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1 wherein the antibody or antigen-binding fragment thereof binds to human TTR monomers and/or human TTR fibrils.

### Claim 3 (depends on 1)

The antibody or antigen-binding fragment of claim 1, wherein the antibody or antigen-binding fragment is an antigen-binding fragment, wherein the antigen-binding fragment comprises a Fab, Fab′, F(ab′)2, single chain Fv(scFv), disulfide linked Fv, intrabody, minibody, F(ab′)3, 2 tetrabody, triabody, diabody, single domain antibody, DVD-Ig, Fcab, mAb2, (scFv)2, or scFv-Fc.

### Claim 4 (depends on 1)

An isolated polynucleotide comprising a first nucleic acid molecule encoding the heavy chain variable region or heavy chain of the antibody or antigen-binding fragment thereof of claim 1 and a second nucleic acid molecule encoding the light chain variable region or light chain of the antibody or antigen-binding fragment thereof of claim 1.

### Claim 5 (depends on 4)

An isolated vector comprising the polynucleotide of claim 4.

### Claim 6 (depends on 4)

A host cell comprising the polynucleotide of claim 4.

### Claim 7 (depends on 4)

A method of producing an antibody or antigen-binding fragment thereof that binds to human TTR comprising culturing the host cell comprising the isolated polynucleotide of claim 4 so that the first nucleic acid molecule and the second nucleic acid molecule are expressed and the antibody or antigen-binding fragment thereof is produced.

### Claim 8 (depends on 7)

An isolated antibody or antigen-binding fragment thereof that is produced by the method of claim 7.

### Claim 9 (depends on 1)

A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable excipient.

### Claim 10 (depends on 1)

A method for detecting TTR in a sample or precipitating TTR from a sample comprising contacting the sample with the antibody or antigen-binding fragment thereof of claim 1.

### Claim 11 (depends on 1)

A method for increasing the uptake of TTR aggregates by an immune cell exposed to TTR aggregates comprising contacting the immune cell with the antibody or antigen-binding fragment of claim 1.

### Claim 12 (depends on 1)

A method for decreasing the toxicity of TTR aggregates on a cell exposed to TTR aggregates comprising contacting the cell with the antibody or antigen-binding fragment thereof of claim 1.

### Claim 13 (depends on 1)

A method of inhibiting the accumulation of TTR aggregates in an organ exposed to TTR aggregates comprising contacting the organ with the antibody or antigen-binding fragment thereof of claim 1.

### Claim 14 (depends on 1)

A method of treating a TTR amyloidosis in a subject comprising administering to the subject the antibody or antigen-binding fragment thereof of claim 1.

### Claim 15 (depends on 1)

A method for diagnosing a TTR amyloidosis in a subject comprising administering to the subject the antibody or antigen-binding fragment thereof of claim 1.

### Claim 16 (depends on 1)

A kit comprising the antibody or antigen-binding fragment thereof of claim 1 and a) a detection reagent, b) TTR antigen, c) a notice that reflects approval for use or sale for human administration, or d) a combination thereof.