# US 10,370,433 B2 · Compositions and methods for diagnosis and treatment of cancer

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- Number: US 10,370,433 B2
- Document ID: US10370433B2
- Status: Granted
- Kind: B2
- Application number: 15/552,215
- Filed: 2016-03-15
- Published: 2018-02-08
- Granted: 2019-08-06
- Earliest claimed: 2015-03-17
- Assignees: BioNTech SE
- Applicants: Biontech AG
- Inventors: Ugur Sahin; Joycelyn Wüstehube-Lausch; Markus Fiedler; Matin Daneschdar; Hans-Ulrich Schmoldt
- Web page: https://patentgrep.com/patent/US10370433B2

## CPC

- C07K 14/811: {Serine protease (E.C. 3.4.21) inhibitors}
- A61P 35/00: Antineoplastic agents
- C12Y 304/21026: Prolyl oligopeptidase (3.4.21.26), i.e. proline-specific endopeptidase
- 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
- C12Y: ENZYMES

## Abstract

The present invention relates to the diagnosis and treatment of cancerous diseases, in particular cancerous diseases expressing Seprase (Fap-alpha; fibroblast activation protein alpha). More particularly, the invention concerns peptides targeting Seprase.

## Claims

### Claim 1

A Seprase binding peptide which comprises the amino acid sequence Gly Arg Gly Pro (SEQ ID NO: 5), wherein
(a) the Seprase binding peptide forms and/or is part of a cystine knot structure containing at least three disulphide bridges formed from pairs of cysteine molecules, and
(b) the amino acid sequence Gly Arg Gly Pro (SEQ ID NO: 5) is part of the cystine knot structure wherein the amino acid sequence is located between the first cysteine and the second cysteine of the cystine knot structure.

### Claim 2 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 6)
Tyr Xaa1 Xaa2 Trp Xaa3 Xaa4 Gly Arg Gly Pro
wherein
Xaa1 is any amino acid,
Xaa2 is any amino acid,
Xaa3 is any amino acid,
Xaa4 is any amino acid.

### Claim 3 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 7)
Tyr Xaa1 Asn Trp Thr Pro Gly Arg Gly Pro
wherein
Xaa1 is any amino acid.

### Claim 4 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 8)
Tyr Ser Asn Trp Thr Pro Gly Arg Gly Pro.

### Claim 5 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(Xaa)n1 Cys (Xaa)n2 Gly Arg Gly Pro (Xaa)n3 Cys
(Xaa)n4 Cys (Xaa)n5 Cys (Xaa)n6 Cys (Xaa)n7 Cys
(Xaa)n8
wherein
the Cys residues form a cystine knot structure,
Xaa is independently from each other any amino acid and
n1, n2, n3, n4, n5, n6, n7, and n8 are the respective numbers of amino acids,
wherein the nature of the amino acids Xaa and/or the number of amino acids n1, n2, n3, n4, n5, n6, n7 and n8 are such that a cystine knot structure can form between the Cys residues,
wherein
n1 is 0 to 4,
n2 is 3 to 10,
n3 is 0 to 4,
n4 is 3 to 7,
n5 is 2 to 6,
n6 is 1 to 3,
n7 is 3 to 7, and
n8 is 0 to 4.

### Claim 6 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 17)
Cys Xaa1 Tyr Xaa2 Xaa3 Trp Xaa4 Xaa5 Gly Arg Gly
Pro Xaa6 Cys Arg Arg Asp Ser Asp Cys Pro Gly Xaa7
Cys Ile Cys Arg Gly Asn Gly Tyr Cys
wherein
Xaa1 is any amino acid,
Xaa2 is any amino acid,
Xaa3 is any amino acid,
Xaa4 is any amino acid,
Xaa5 is any amino acid,
Xaa6 is any amino acid,
Xaa7 is any amino acid.

### Claim 7 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 18)
Cys Pro Tyr Xaa1 Asn Trp Thr Pro Gly Arg Gly Pro
Xaa2 Cys Arg Arg Asp Ser Asp Cys Pro Gly Xaa3
Cys Ile Cys Arg Gly Asn Gly Tyr Cys
wherein
Xaa1 is any amino acid,
Xaa2 is any amino acid,
Xaa3 is any amino acid.

### Claim 8 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 19)
Cys Pro Tyr Ser Asn Trp Thr Pro Gly Arg Gly Pro
Asp Cys Arg Arg Asp Ser Asp Cys Pro Gly Arg Cys
Ile Cys Arg Gly Asn Gly Tyr Cys.

### Claim 9 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 12)
Xaa1 Xaa2 Cys Xaa3 Tyr Xaa4 Xaa5 Trp Xaa6 Xaa7 Gly
Arg Gly Pro Xaa8 Cys Arg Arg Asp Ser Asp Cys Pro
Gly Xaa9 Cys Ile Cys Arg Gly Asn Gly Tyr Cys Gly
wherein
Xaa1 is any amino acid,
Xaa2 is any amino acid,
Xaa3 is any amino acid,
Xaa4 is any amino acid,
Xaa5 is any amino acid,
Xaa6 is any amino acid,
Xaa7 is any amino acid,
Xaa8 is any amino acid,
Xaa9 is any amino acid.

### Claim 10 (depends on 1)

The Seprase binding peptide of claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 21)
Xaa1 Xaa2 Cys Pro Tyr Xaa3 Asn Trp Thr Pro Gly Arg
Gly Pro Xaa4 Cys Arg Arg Asp Ser Asp Cys Pro Gly
Xaa5 Cys Ile Cys Arg Gly Asn Gly Tyr Cys Gly
wherein
Xaa1 is any amino acid,
Xaa2 is any amino acid,
Xaa3 is any amino acid,
Xaa4 is any amino acid,
Xaa5 is any amino acid.

### Claim 11 (depends on 1)

The Seprase binding peptide claim 1, which comprises the amino acid sequence:
(SEQ ID NO: 22)
Gly Lys Cys Pro Tyr Ser Asn Trp Thr Pro Gly Arg
Gly Pro Asp Cys Arg Arg Asp Ser Asp Cys Pro Gly
Arg Cys Ile Cys Arg Gly Asn Gly Tyr Cys Gly.

### Claim 12

A Seprase binding peptide comprising the amino acid sequence:
(SEQ ID NO: 23)
Gly Ala Cys Pro Tyr Ser Asn Trp Thr Pro Gly Arg
Gly Pro Asp Cys Arg Arg Asp Ser Asp Cys Pro Gly
Arg Cys Ile Cys Arg Gly Asn Gly Tyr Cys Gly.

### Claim 13 (depends on 1)

The Seprase binding peptide of claim 1, wherein the cystine knot structure is based on the open chain trypsin inhibitor II from Momordica cochinchinensis (MCoTI-II).

### Claim 14

A Seprase binding peptide comprising the amino acid sequence Gly Arg Gly Pro (SEQ ID NO: 5) and at least one fusion partner.

### Claim 15 (depends on 14)

The Seprase binding peptide of claim 14, wherein the fusion partner comprises a heterologous amino acid sequence.

### Claim 16

A Seprase binding agent comprising the amino acid sequence Gly Arg Gly Pro (SEQ ID NO: 5) covalently and/or non-covalently associated with at least one further moiety.