# US 2019/0169295 A1 · Long life polypeptide binding molecules

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- Number: US 2019/0169295 A1
- Document ID: US20190169295A1
- Status: Published application
- Kind: A1
- Application number: 16/126,617
- Filed: 2018-09-10
- Published: 2019-06-06
- Earliest claimed: 2012-03-01
- Assignees: Amgen Research (Munich) GmbH
- Applicants: Amgen Research (Munich) GmbH
- Inventors: Peter Kufer; Tobias Raum; Ralf Lutterbüse; Markus Münz; Johannes Brozy; Majk Kvesic; Patrick Hoffmann
- Web page: https://patentgrep.com/patent/US20190169295A1

## CPC

- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/26: against hormones {; against hormone releasing or inhibiting factors}
- C07K 16/30: from tumour cells
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07K 2317/31: multispecific
- 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 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/622: Single chain antibody (scFv)
- 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
- C07K 2319/31: fusions, other than Fc, for prolonged plasma life, e.g. albumin
- C07K 2319/32: fusions with soluble part of a cell surface receptor, "decoy receptors"
- 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

## Abstract

The present invention relates to a binding molecule comprising at least three domains comprised in at least one polypeptide chain, wherein the first binding domain is a binding domain which is capable of binding to a cell surface molecule on a target cell, the second binding domain is a binding domain which is capable of binding to the T cell CD3 receptor complex, and the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

## Claims

### Claim 1

A binding molecule comprising at least three binding domains comprised in at least one polypeptide chain, wherein
(a) the first domain is a binding domain which is capable of binding to a cell surface molecule on a target cell; and
(b) the second domain is a binding domain which is capable of binding to the T cell CD3 receptor complex; and
(c) the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain.

### Claim 2 (depends on 1)

The binding molecule according to claim 1, wherein the three domains are on one polypeptide in the order from the N-terminus to the C-terminus
the first binding domain;
the second binding domain; and
the third binding domain.

### Claim 3 (depends on 1)

The binding molecule according to claim 1,
wherein the third binding domain of the binding molecule is an scFv or a single domain antibody.

### Claim 4 (depends on 1)

The binding molecule according to claim 1, wherein
(a) the first binding domain is capable of binding to the cell surface molecule on a human and a non-human primate cell;
(b) the second binding domain is capable of binding to the T cell CD3 receptor complex on a human and a non-human primate cell, and
(c) the third binding domain is capable of binding to human and non-human primate serum albumin.

### Claim 5 (depends on 1)

The binding molecule according to claim 1, wherein the third binding domain capable of binding to serum albumin is derived from a combinatorial library or an antibody binding domain.

### Claim 6 (depends on 1)

The binding molecule according to claim 1, wherein the third binding domain comprises between 10 and 25 amino acid residues.

### Claim 7 (depends on 1)

The binding molecule according to claim 1, wherein the third binding domain capable of binding to serum albumin comprises the amino acid sequence Asp-Xaa-Cys-Leu-Pro-Xaa-Trp-Gly-Cys-Leu-Trp (SEQ ID NO: 102), wherein Xaa is any amino acid.

### Claim 8 (depends on 1)

The binding molecule according to claim 1, wherein the third binding domain capable of binding to serum albumin is derived from a CDR of a single domain antibody.

### Claim 9 (depends on 1)

The binding molecule according to claim 1, wherein the third binding domain is binding to serum albumin with an affinity (KD) of <500 nM.

### Claim 10 (depends on 1)

The binding molecule according to claim 1, wherein the binding molecule shows cytotoxic activity in an in vitro assay measuring the lysis of target cells by effector cells in the presence of 10% human serum albumin.

### Claim 11 (depends on 1)

The binding molecule according to claim 1, wherein the molecule consists of a single polypeptide chain.

### Claim 12 (depends on 1)

The binding molecule according to claim 1, wherein
(a) the first binding domain comprises an antibody derived VL and VH chain; and/or
(b) the second binding domain comprises an antibody derived VL and VH chain.

### Claim 13 (depends on 1)

The binding molecule according to claim 1, wherein the molecule comprises one or more further heterologous polypeptide.

### Claim 14 (depends on 1)

The binding molecule according to claim 1, wherein the first-binding domain capable of binding to a cell surface molecule is binding to a tumor antigen.

### Claim 15 (depends on 1)

The binding molecule according to claim 1, wherein the second binding domain capable of binding to the T cell CD3 receptor complex is capable of binding-to an epitope of human and Callithrix jacchus, Saguinus oedipus or Saimiri sciureus CD3ε chain, wherein the epitope is part of an amino acid sequence of SEQ ID NO: 2, 4, 6, or 8 and comprises at least the amino acid sequence Gln-Asp-Gly-Asn-Glu (SEQ ID NO: 103).

### Claim 16 (depends on 1)

The binding molecule according to claim 1, characterized by the amino acid sequence set forth in SEQ ID NO: 51, 52, 54, 55, 57, 58, 60, 61, 75, 76, 81, 82, 85, 86, 90, 91, 85, 96, 100 or 101.

### Claim 17 (depends on 1)

A nucleic acid encoding the binding molecule of claim 1.

### Claim 18 (depends on 17)

A vector comprising the nucleic acid of claim 17.

### Claim 19 (depends on 17)

A host cell transformed or transfected with the nucleic acid of claim 17.

### Claim 20 (depends on 19)

A process for producing a binding molecule, said process comprising culturing the host cell of claim 19 under suitable conditions to express the binding molecule and, optionally, recovering the binding molecule from the culture.

### Claim 21 (depends on 1, 20)

A pharmaceutical composition comprising the binding molecule of claim 1, or produced according to the process of claim 20.

### Claim 22

(canceled)

### Claim 23 (depends on 1)

A method for treating or ameliorating a disease selected from the group consisting of a proliferative disease, an inflammatory disease, an infectious disease and an autoimmune disease, comprising the step of administering to a subject in need thereof the binding molecule of claim 1.

### Claim 24 (depends on 1)

A kit comprising the binding molecule of claim 1.