# US 9,872,891 B2 · Peptides for the treatment of cancer

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- Number: US 9,872,891 B2
- Document ID: US9872891B2
- Status: Granted
- Kind: B2
- Application number: 15/286,272
- Filed: 2016-10-05
- Published: 2017-02-16
- Granted: 2018-01-23
- Earliest claimed: 2013-01-11
- Assignees: Newfield Therapeutics Corporation
- Applicants: Newfield Therapeutics Corporation
- Inventors: Dagmar Zweytick; Karl Lohner; Sabrina Riedl
- Web page: https://patentgrep.com/patent/US9872891B2

## CPC

- A61K 38/40: Transferrins, e.g. lactoferrins, ovotransferrins
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61P 25/00: Drugs for disorders of the nervous system
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/79: Transferrins, e.g. lactoferrins, ovotransferrins
- 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
- 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 present invention relates to an isolated peptide for use in the treatment of cancer consisting of 12 to 50 amino acid residues comprising: at least two beta-strands, or at least two alpha-helices, or at least one beta-strand and at least one alpha-helix; wherein said beta-strands and/or alpha-helices are preferably separated from each other by at least one turn, wherein the peptide has a net positive charge of +7 or more; wherein said peptide comprises at least one peptide moiety having amino acid sequence (X1)M-X2-(X3)P-X4-(X5)Q-X6-(X7)S or the reverse sequence thereof, wherein X1 is a hydrophobic amino acid, preferably selected from the group consisting of phenylalanine (Phe), alanine (Ala), leucine (Leu) and valine (Val), X2 is a hydrophobic amino acid, preferably tryptophan (Trp), X3 is selected from the group consisting of alanine (Ala), arginine (Arg), glutamine (Gln), asparagine (Asn), proline (Pro), isoleucine (Ile), leucine (Leu) and valine (Val), X4 is selected from the group consisting of isoleucine (Ile), phenylalanine (Phe), tryptophan (Trp) and tyrosine (Tyr), X5 is selected from the group consisting of arginine (Arg), lysine (Lys), tyrosine (Tyr) and phenylalanine (Phe), X6 is a hydrophobic amino acid, preferably selected from the group consisting of isoleucine (Ile), tryptophan (Trp), valine (Val) and leucine (Leu), and X7 is selected from the group consisting of arginine (Arg), lysine (Lys), isoleucine (Ile) and serine (Ser), and wherein M is 1 or 2, Q is 1 or 2, P is 2 or 3, and S is 1, 2, 3 or 4 under the proviso that if (X5)Q is Arg-Arg S is 1; and wherein said peptide is devoid of intramolecular disulfide bonds.

## Claims

### Claim 1

A method of treating cancer comprising administering an isolated peptide that is 12 to 50 amino acids in length comprising at least two peptide moieties, wherein said at least two peptide moieties are:
(a) at least two beta-strands;
(b) at least two alpha-helices; or
(c) at least one beta-strand and at least one alpha-helix,
wherein said beta-strands and/or alpha-helices are separated from each other by at least one turn;
wherein the peptide has a net positive charge of +7 or more;
wherein the peptide moieties have an amino acid sequence, selected from the group consisting of FWQRIRKVR (SEQ ID No. 1), FWQRRIRKVRR (SEQ ID No. 2), FWQRKIRKVRK (SEQ ID No. 3), FWQRNIRIRR (SEQ ID No. 4), FWQRNIRKVR (SEQ ID No. 5), FWQRNIRVR (SEQ ID No. 6), FWQRNIRKVRR (SEQ ID No. 7), FWQRNIRKVKK (SEQ ID No. 8), FWQRNIRKVRRR (SEQ ID No. 9), FWQRNIRKVKKK (SEQ ID No. 10), FWQRNIRKVRRRR (SEQ ID No. 11), FWQRNIRKVRRRI (SEQ ID No. 12), FWQRNIRKVKKKK (SEQ ID No. 13), FWQRNIRKVKKKI (SEQ ID No. 14), FWQRNIRKIR (SEQ ID No. 15), FWQRNIRKLR (SEQ ID No. 16), FWQRNIRKWR (SEQ ID No. 17), FWQRNWRKVR (SEQ ID No. 18), FWQRNFRKVR (SEQ ID No. 19), FWQRNYRKVR (SEQ ID No. 20), FWQRNIRKVS (SEQ ID No. 21), FWQRRIRIRR (SEQ ID No. 22), FWQRPIRKVR (SEQ ID No. 23), FWQRRIRKWR (SEQ ID No. 24), FWPRNIRKVR (SEQ ID No. 26), FWARNIRKVR (SEQ ID No. 27), FWIRNIRKVR (SEQ ID No. 28), FWLRNIRKVR (SEQ ID No. 29), FWVRNIRKVR (SEQ ID No. 30), FWQRNIFKVR (SEQ ID No. 31), FWQRNIYKVR (SEQ ID No. 32), FAWQRNIRKVR (SEQ ID No. 33), FIWQRNIRKVR (SEQ ID No. 34), FLWQRNIRKVR (SEQ ID No. 35), FVWQRNIRKVR (SEQ ID No. 36), FWRIRKWR (SEQ ID No. 37), FWRIRKVR (SEQ ID No. 38), FWRWRR (SEQ ID No. 39), FWRRWRR (SEQ ID No. 40), FWRRWIRR (SEQ ID No. 41), FWRGWRIRR (SEQ ID No. 42), FWRRFWRR (SEQ ID No. 43), FWRWRWR (SEQ ID No. 44), FWRIWRWR (SEQ ID No. 45), FWRIWRIWR (SEQ ID No. 46), FWRNIRKWR (SEQ ID No. 47), FWRRRIRIRR (SEQ ID No. 48), FIWRWRWR (SEQ ID No. 49), PFWRWRIWR (SEQ ID No. 50), PFWRIRIRR (SEQ ID No. 51), PFWRQRIRR (SEQ ID No. 52), PFWRARIRR (SEQ ID No. 53), PFWRKRIRR (SEQ ID No. 54), PFWRKRLRR (SEQ ID No. 55), PFWRKRWRR (SEQ ID No. 56), PFWRRRIRR (SEQ ID No. 57), PFWRRRWRR (SEQ ID No. 58), PFWRIRIRRD (SEQ ID No. 59), PFFWRIRIRR (SEQ ID No. 60), PWRIRIRR (SEQ ID No. 61), RFWQRNIRKVRR (SEQ ID No. 62), RFWQRNIRKYR (SEQ ID No. 63), PFWQRNIRKWR (SEQ ID No. 64), RFRWQRNIRKYRR (SEQ ID No. 65), RWKRINRQWF (SEQ ID No. 66), KRFCFKK (SEQ ID No. 67), KRFSFKKC (SEQ ID No. 68), KRWSWKK (SEQ ID No. 69), FRFSFKK (SEQ ID No. 70), RRFWFRR (SEQ ID No. 71), FWRNIRIRR (SEQ ID No. 72), FWQRIRIRR (SEQ ID No. 73), FWRWRIWR (SEQ ID No. 74), FWRIRIRR (SEQ ID No. 75), FWRNIRIWRR (SEQ ID No. 76) and FWRNIRIRR (SEQ ID No. 77), RFWQRNIRIRR (SEQ ID No. 78), RWQRNIRIRR (SEQ ID No. 79), RRIRINRQWF (SEQ ID No. 80), PFWRRQIRR (SEQ ID No. 81), PFWRKKLKR (SEQ ID No. 82), PWRRIRR (SEQ ID No. 83), PWRRKIRR (SEQ ID No. 84), PFWRRIRIRR (SEQ ID No. 85), and RRWFWRR (SEQ ID No. 86), FWQRRIRRWRR (SEQ ID No. 112), PFWRRRIRIRR (SEQ ID No. 193), RRWFFWRR (SEQ ID No. 198) and the reverse sequences thereof; and
wherein said peptide is devoid of intramolecular disulfide bonds; and
wherein the cancer is selected from the group consisting of melanoma, rhabdomyosarcoma, glioblastoma, colorectal cancer, breast cancer, lymphoma, prostate cancer, pancreatic cancer, renal cancer, ovarian cancer, and lung cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein the peptide is selected from the group consisting of PFWRIRIRRXRRIRIRWFP (SEQ ID. No. 128), PWRIRIRRXRRIRIRWP (SEQ ID No. 184), RWKRINRQWFFWQRNIRKWR (SEQ ID. No. 106), PFWRIRIRRPFWRIRIRR (SEQ ID. No. 125), PFFWRIRIRRPFFWRIRIRR (SEQ ID. No. 141) and PFWRIRIRRRRIRIRWFP (SEQ ID. No. 127).

### Claim 3 (depends on 2)

The method of claim 2, wherein the peptide is selected from the group consisting of SEQ ID. Nos. 128, 184 and 106, wherein “X” is proline (Pro) and/or glycine (Gly)1-3.

### Claim 4 (depends on 1)

The method of claim 1, wherein the peptide is devoid of cysteine residues.

### Claim 5 (depends on 1)

The method of claim 1, wherein the isolated peptide comprises at least two peptide moieties having the same amino acid sequence, wherein the at least two peptide moieties are fused directly or via a linker to each other.

### Claim 6 (depends on 5)

The method of claim 5, wherein the isolated peptide comprises two peptide moieties having the same amino acid sequence, wherein the at least two peptide moieties are fused directly or via a linker to each other.

### Claim 7 (depends on 1)

The method of claim 1, wherein the isolated peptide comprises at least two peptide moieties, wherein the at least one second peptide moiety is the reverse sequence thereof, wherein the at least two peptide moieties are fused directly or via a linker to each other.

### Claim 8 (depends on 7)

The method of claim 7, wherein the isolated peptide comprises two peptide moieties, wherein the at least one second peptide moiety is the reverse sequence thereof, wherein the at least two peptide moieties are fused directly or via a linker to each other.

### Claim 9 (depends on 1)

The method of claim 1, wherein the cancer is melanoma, rhabdomyosarcoma, or glioblastoma cancer.

### Claim 10 (depends on 1)

The method of claim 1, wherein the peptide moieties have an amino acid sequence, selected from the group consisting of FWQRNIRIRR (SEQ ID No. 4), FWQRNIRKWR (SEQ ID No. 17), FWQRRIRKWR (SEQ ID No. 24), FWRRFWRR (SEQ ID No. 43), FWRNIRKWR (SEQ ID No. 47), PFWRIRIRR (SEQ ID No. 51), PFWRQRIRR (SEQ ID No. 52), PFWRARIRR (SEQ ID No. 53), PFWRKRIRR (SEQ ID No. 54), PFWRKRLRR (SEQ ID No. 55), PFWRKRWRR (SEQ ID No. 56), PFWRRRIRR (SEQ ID No. 57), PFWRRRWRR (SEQ ID No. 58), PFWRIRIRRD (SEQ ID No. 59), PFFWRIRIRR (SEQ ID No. 60), PWRIRIRR (SEQ ID No. 61), PFWQRNIRKWR (SEQ ID No. 64), RWKRINRQWF (SEQ ID No. 66), FWRIRIRR (SEQ ID No. 75), RRIRINRQWF (SEQ ID No. 80), PFWRRQIRR (SEQ ID No. 81), PFWRKKLKR (SEQ ID No. 82), PWRRIRR (SEQ ID No. 83), PWRRKIRR (SEQ ID No. 84), RRWFWRR (SEQ ID No. 86), PFWRRRIRIRR (SEQ ID No. 193), and RRWFFWRR (SEQ ID No. 198), and the reverse sequences thereof.

### Claim 11 (depends on 10)

The method of claim 10, wherein the cancer is melanoma, rhabdomyosarcoma, or glioblastoma cancer.