# US 8,785,390 B2 · Methods for treatment of Alzheimer's disease

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- Number: US 8,785,390 B2
- Document ID: US8785390B2
- Status: Granted
- Kind: B2
- Application number: 13/145,096
- Filed: 2010-01-29
- Published: 2012-05-17
- Granted: 2014-07-22
- Earliest claimed: 2009-01-30
- Assignees: Alphabeta AB
- Applicants: Jan Johansson
- Inventors: Jan Johansson
- Web page: https://patentgrep.com/patent/US8785390B2

## CPC

- A61K 38/395: {Alveolar surfactant peptides; Pulmonary surfactant peptides}
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07K 14/785: Alveolar surfactant peptides; Pulmonary surfactant peptides
- 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)
- A61K 38/1709: {from mammals}
- 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

An isolated protein selected from the group consisting of (i) proteins comprising an amino acid sequence having at least 70% identity to the C-terminal domain of lung surfactant protein C precursor (CTproSP-C, “CTC”) from a mammal; and (ii) proteins comprising an amino acid sequence having at least 70% identity to the Brichos domain of CTproSP-C from a mammal, is disclosed for treatment of Alzheimer's disease in a mammal, including man.

## Claims

### Claim 1

A method of therapeutically treating or delaying progression of Alzheimer's disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an isolated protein, wherein the isolated protein delays or reduces amyloid fibril formation and aggregation of amyloid β peptide, and wherein the isolated protein is selected from:
(a) a protein comprising an amino acid sequence having all conserved residues of mammalian C-terminal domain of lung surfactant protein C precursor (CTproSP-C) (SEQ ID NO: 11) and having at least 70% identity to the CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); or
(b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 70% identity to the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17).

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject is human.

### Claim 3 (depends on 1)

The method of claim 1, wherein the isolated protein is selected from:
(a) a protein comprising an amino acid sequence having all conserved residues of mammalian C-terminal domain of lung surfactant protein C precursor (CTproSP-C) (SEQ ID NO: 11) and having at least 70% identity to human CTproSP-C (SEQ ID NO: 2); or
(b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 70% identity to the Brichos domain of human CTproSP-C (SEQ ID NO: 4).

### Claim 4 (depends on 1)

The method of claim 1, wherein the isolated protein has less than or equal to 200 amino acid residues.

### Claim 5 (depends on 4)

The method of claim 4, wherein the isolated protein has less than or equal to 150 amino acid residues.

### Claim 6 (depends on 1)

The method of claim 1, wherein the isolated protein has more than or equal to 90 amino acid residues.

### Claim 7 (depends on 6)

The method of claim 6, wherein the isolated protein has more than or equal to 100 amino acid residues.

### Claim 8 (depends on 1)

The method of claim 1, wherein the isolated protein is selected from the group consisting of:
(a) CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10);
(b) the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17); and
(c) an extended Brichos domain of human CTproSP-C having the amino acid sequence of SEQ ID NO: 21.

### Claim 9 (depends on 8)

The method of claim 8, wherein the isolated protein is selected from the group consisting of human CTproSP-C (SEQ ID NO: 2), the Brichos domain of human CTproSP-C (SEQ ID NO: 4), and the extended Brichos domain of human CTproSP-C having SEQ ID NO: 21.

### Claim 10 (depends on 1)

The method of claim 1, wherein a position corresponding to leucine-188 in human proSP-C (SEQ ID NO: 1) is not glutamine.

### Claim 11 (depends on 10)

The method of claim 10, wherein the position corresponding to leucine-188 in human proSP-C (SEQ ID NO: 1) is strictly conserved.

### Claim 12 (depends on 1)

The method of claim 1, wherein the isolated protein comprises an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 or SEQ ID NO: 16.

### Claim 13 (depends on 1)

The method of claim 1, wherein the isolated protein is selected from:
(a) a protein comprising an amino acid sequence having all conserved residues of mammalian CTproSP-C (SEQ ID NO: 11) and having at least 80% identity to the CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); or
(b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 80% identity to the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17).

### Claim 14 (depends on 13)

The method of claim 13, wherein the isolated protein comprises an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 or SEQ ID NO: 16.

### Claim 15 (depends on 13)

The method of claim 13, wherein the isolated protein is selected from:
(a) a protein comprising an amino acid sequence having all conserved residues of mammalian CTproSP-C (SEQ ID NO: 11) and having at least 90% identity to the CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); or
(b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 90% identity to the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17).

### Claim 16 (depends on 15)

The method of claim 15, wherein the isolated protein comprises an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 or SEQ ID NO: 16.

### Claim 17 (depends on 1)

The method of claim 1, wherein the isolated protein is selected from:
(a) a protein comprising an amino acid sequence having all conserved residues of mammalian CTproSP-C (SEQ ID NO: 11) and having at least 70% identity and at least 90% similarity to the CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); or
(b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 70% identity and at least 90% similarity to the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17).