# US 11,299,526 B2 · p53-BAD fusion proteins

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- Number: US 11,299,526 B2
- Document ID: US11299526B2
- Status: Granted
- Kind: B2
- Application number: 16/414,683
- Filed: 2019-05-16
- Published: 2019-12-05
- Granted: 2022-04-12
- Earliest claimed: 2018-05-16
- Assignees: University of Utah Research Foundation
- Applicants: University of Utah Research Foundation
- Inventors: Carol S. Lim; Phong Lu
- Web page: https://patentgrep.com/patent/US11299526B2

## CPC

- C07K 14/4747: {Apoptosis related proteins}
- A61P 35/00: Antineoplastic agents
- C07K 14/4746: {p53}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/00: Fusion polypeptide
- 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
- 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)

## Abstract

Disclosed are peptides comprising a p53 peptide and a BH3-only protein. In some aspects, wherein the BH3-only protein is BAD, BID, BIM, NOXA. Disclosed are nucleic acid sequences comprising a sequence capable of encoding a p53 peptide operably linked to a nucleic acid sequence capable of encoding a BH3-only protein. Disclosed are nucleic acid sequences comprising a sequence capable of encoding one or more of the peptides disclosed herein. Disclosed are vectors comprising a nucleic acid sequence, wherein the nucleic acid sequence is capable of encoding one or more of the peptides disclosed herein. Also disclosed are methods of using the disclosed peptides, nucleic acid sequences, and vectors.

## Claims

### Claim 1

A peptide comprising a p53 peptide and BAD, wherein the p53 is N-terminal to the BAD.

### Claim 2 (depends on 1)

The peptide of claim 1, wherein BAD comprises the amino acid sequence of
(SEQ ID NO: 1)
MFQIPEFEPSEQEDSSSAERGLGPSPAGDGPSGSGKHHRQA
PGLLWDASHQQEQPTSSSHHGGAGAVEIRSRHSSYPAGTED
DEGMGEEPSPFRGRSRSAPPNLWAAQRYGRELRRMSDEFVD
SFKKGLPRPKSAGTATQMRQSSSWTRVFQSWWDRNLGRGSS
APSQ.

### Claim 3 (depends on 1)

The peptide of claim 1, wherein BAD is a mutated BAD.

### Claim 4 (depends on 3)

The peptide of claim 3, wherein the mutated BAD has a serine to alanine substitution at one or more of positions 75, 99, and 118 of SEQ ID NO:1.

### Claim 5 (depends on 3)

The peptide of claim 3, wherein the mutated BAD has a serine to alanine substitution at positions 75 and 99 of SEQ ID NO:1.

### Claim 6 (depends on 5)

The peptide of claim 5, wherein the mutated BAD has an amino acid sequence of
(SEQ ID NO: 2)
MFQIPEFEPSEQEDSSSAERGLGPSPAGDGPSGSGKHHRQA
PGLLWDASHQQEQPTSSSHHGGAGAVEIRSRHSAYPAGTED
DEGMGEEPSPFRGRSRAAPPNLWAAQRYGRELRRMSDEFVD
SFKKGLPRPKSAGTATQMRQSSSWTRVFQSWWDRNLGRGSS
APSQ.

### Claim 7 (depends on 1)

The peptide of claim 1, wherein the p53 peptide is a full length p53.

### Claim 8 (depends on 1)

The peptide of claim 1, wherein the p53 peptide is a partial p53 peptide, wherein the partial p53 peptide retains pro-apoptotic function.

### Claim 9 (depends on 1)

The peptide of claim 1, further comprising a linker between the p53 peptide and BAD.

### Claim 10 (depends on 9)

The peptide of claim 9, wherein the linker is (GGGGS)3 (SEQ ID NO:9), (PAPAPA)3 (SEQ ID NO:10), (EAAAK)3 (SEQ ID NO:11), or [LEA(EAAAK)4]2LE (SEQ ID NO:12).

### Claim 11 (depends on 8)

The peptide of claim 8, wherein the partial p53 peptide consists of the DNA binding domain of p53.

### Claim 12 (depends on 8)

The peptide of claim 8, wherein the partial p53 peptide consists of amino acids 102-292 of SEQ ID NO:3.

### Claim 13 (depends on 8)

The peptide of claim 8, wherein the partial p53 peptide comprises the DNA binding domain of p53.

### Claim 14 (depends on 8)

The peptide of claim 8, wherein the partial p53 peptide further comprises a MDM2 binding domain, a proline-rich domain, a tetramerization domain, or a transactivation domain of p53.

### Claim 15

A nucleic acid sequence comprising a sequence capable of encoding a p53 peptide operably linked to a nucleic acid sequence capable of encoding BAD, wherein the sequence capable of encoding a p53 peptide is 5′ to the sequence capable of encoding BAD.