# US 2016/0355573 A1 · Gene therapy for alzheimer's and other neurodegenerative diseases and conditions

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2016/0355573 A1
- Document ID: US20160355573A1
- Status: Published application
- Kind: A1
- Application number: 14/911,400
- Filed: 2014-09-05
- Published: 2016-12-08
- Earliest claimed: 2013-09-05
- Assignees: Cornell University
- Applicants: Cornell University
- Inventors: Ronald G. Crystal; Steven M. Paul
- Web page: https://patentgrep.com/patent/US20160355573A1

## CPC

- C07K 16/18: against material from animals or humans
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- A61K 48/0075: {characterised by an aspect of the delivery route, e.g. oral, subcutaneous}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 2039/505: {comprising antibodies}
- 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 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2750/14121: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- 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)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Gene therapy compositions and methods to inhibit or treat neurodegenerative diseases, e.g., Alzheimer's disease, are provided.

## Claims

### Claim 1

An isolated recombinant nucleic acid sequence comprising an open reading frame which encodes an antibody directed against tau, wherein the open reading frame comprises nucleic acid sequences for an Ig heavy chain specific for tau and nucleic acid sequences for an Ig light chain specific for tau.

### Claim 2 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 further comprising nucleic acid sequences for a protease cleavage recognition site interposed between the nucleic acid sequences for the Ig heavy chain and the nucleic acid sequences for the Ig light chain.

### Claim 3 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the heavy chain is an IgG heavy chain or wherein the light chain is an Igκ light chain.

### Claim 4

(canceled)

### Claim 5 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the nucleic acid sequences for the Ig heavy chain have at least 80% nucleic acid sequence identity to the heavy chain sequence in any one of SEQ ID Nos. 1, 2, 5, or 6 or wherein the nucleic acid sequences for the Ig light chain have at least 80% nucleic acid sequence identity to the light chain sequence in any one of SEQ ID Nos. 1, 2, 5 or 6.

### Claim 6

(canceled)

### Claim 7 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the Ig heavy chain has at least 80% amino acid sequence identity to the heavy chain sequence in SEQ ID Nos. 3 or 4 or wherein the Ig light chain has at least 80% amino acid sequence identity to the light chain sequence in SEQ ID Nos. 3 or 4.

### Claim 8

(canceled)

### Claim 9 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the sequences are from MC1 or PHF1.

### Claim 10 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the antibody recognizes phosphorylated tau or a pathological conformation of tau.

### Claim 11 (depends on 10)

The isolated recombinant nucleic acid sequence of claim 10 wherein the antibody recognizes phosphorylated Ser396, Ser404, Ser202, Ser262, Thr205, Ser356, Tyr394, or Tyr310.

### Claim 12 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the antibody recognizes a tau epitope comprising Ala2-Tyr18, Pro312-Glu342, Ser210-Ser241, Arg242-Lys281, Thr220-Ser235, or Arg230-Lys240.

### Claim 13 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the nucleic acid sequences encode an antibody fragment.

### Claim 14 (depends on 13)

The isolated recombinant nucleic acid sequence of claim 13 wherein the fragment is a Fab′ or scFv.

### Claim 15 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the open reading frame is operably linked to a promoter that is expressed in neurons, oligodendrocytes, glial cells or astrocytes.

### Claim 16 (depends on 1)

The isolated recombinant nucleic acid sequence of claim 1 wherein the open reading frame is operably linked to a cytomegalovirus/chicken beta-actin hybrid promoter or a glial fibrillary acidic protein promoter.

### Claim 17

(canceled)

### Claim 18

An adeno-associated virus or lentivirus comprising nucleic acid sequences encoding an Ig heavy chain of an anti-tau antibody, an Ig light chain of an anti-tau antibody or an Ig heavy chain of an anti-tau antibody linked to an Ig light chain of an anti-tau antibody.

### Claim 19 (depends on 18)

The virus of claim 18 which is an AAV2 AAV5, AAV6, AAVrh.10, AAV8 or AAV9.

### Claim at position 20

20-21. (canceled)

### Claim 22 (depends on 1)

A method of inhibiting or treating a neurodegenerative disease or condition characterized by pathological tau activity in a mammal, comprising administering to the mammal an effective amount of a composition comprising the recombinant nucleic acid sequence of claim 1, and a pharmaceutically-acceptable carrier.

### Claim 23 (depends on 22)

The method of claim 22 wherein the disease or condition is selected from the group comprising Alzheimer's disease, mild cognitive impairment, frontotemporal dementia, traumatic brain injury, stroke, transient ischemic attack, dementia, Creutzfeldt-Jakob disease, multiple sclerosis, prion disease, Pick's disease, corticobasal degeneration, Parkinson's disease, Lewy body dementia, Progressive supranuclear palsy; Dementia pugilistica (chronic traumatic encephalopathy); frontotemporal dementia and parkinsonism linked to chromosome 17; Lytico-Bodig disease; Tangle-predominant dementia; Ganglioglioma. and gangliocytoma; Meningioangiomatosis; Subacute sclerosing panencephalitis; lead encephalopathy, tuberous sclerosis, Hallervorden-Spatz disease, and lipofuscinosis; Argyrophilic grain disease; and Frontotemporal lobar degeneration.

### Claim 24 (depends on 22)

The method of claim 22 wherein the mammal is a human.

### Claim 25 (depends on 22)

The method of claim 22 wherein the composition is administered intracranially, intraventicularly, or intracisternally.

### Claim 26

(canceled)

### Claim 27 (depends on 24)

The method of claim 24 wherein the human has an ApoE4 allele.

### Claim 28

(canceled)