# US 2019/0169275 A1 · Methods of Treating a Tauopathy

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- Number: US 2019/0169275 A1
- Document ID: US20190169275A1
- Status: Published application
- Kind: A1
- Application number: 16/036,309
- Filed: 2018-07-16
- Published: 2019-06-06
- Earliest claimed: 2012-08-16
- Assignees: iPierian, Inc.
- Applicants: iPierian, Inc.
- Inventors: Irene Griswold-Prenner; Nancy E. Stagliano; Vu Cao Dang
- Web page: https://patentgrep.com/patent/US20190169275A1

## CPC

- C07K 16/18: against material from animals or humans
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- 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 16/461: {Igs containing Ig-regions, -domains or -residues form different species}
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- 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 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22
- G01N 2333/4709: Amyloid plaque core protein
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure provides methods of treating a tauopathy, involving administering an anti-Tau antibody. The present disclosure also provides anti-Tau antibodies, and formulations comprising same, for use in the methods.

## Claims

### Claim at position 1

-62. (canceled)

### Claim 63

A method of monitoring progression of a tauopathy in an individual, the method comprising:
a) determining a first level of a Tau polypeptide in a biological sample obtained from the individual at a first time point;
b) determining a second level of a Tau polypeptide in a biological sample obtained from the individual at a second time point; and
c) comparing the second level of Tau with the first level of Tau, wherein said determining comprises:
i) contacting the biological sample with an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41; and
ii) quantitating binding of the antibody to Tau polypeptide present in the sample.

### Claim 64 (depends on 63)

The method of claim 63, wherein the biological sample is cerebrospinal fluid, blood, plasma, serum, urine, or saliva.

### Claim 65 (depends on 63)

The method of claim 63, wherein the quantitated Tau polypeptide is total Tau polypeptide.

### Claim 66 (depends on 63)

The method of claim 63, wherein the quantitated Tau polypeptide is an N-terminal fragment of a full-length Tau polypeptide.

### Claim 67 (depends on 63)

The method of claim 63, wherein the first time point is a time point before initiation of a treatment regimen, and wherein the second time point is a time point after initiation of a treatment regimen.

### Claim 68

A method of detecting a Tau polypeptide in a living individual in vivo, the method comprising:
a) administering to the individual an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41; and
b) detecting binding of the antibody to tau polypeptide in a brain tissue in the individual using an imaging method.

### Claim 69 (depends on 68)

The method of claim 68, wherein the antibody comprises a contrast agent suitable for use in the imaging method.

### Claim 70 (depends on 68)

The method of claim 68, wherein the imaging method is magnetic resonance imaging or positron emission tomography.

### Claim 71

An in vitro method of detecting a Tau polypeptide in a biological sample obtained from an individual, the method comprising:
a) contacting the biological sample with an antibody competes for binding to an epitope within the N-terminal region of Tau with an antibody that comprises:
i) light chain complementarity-determining regions (CDRs) of an antibody depicted in FIG. 1B; and heavy chain CDRs of an antibody depicted in FIG. 1A; or
ii) light chain CDRs of an antibody depicted in FIG. 2B; and heavy chain CDRs of an antibody depicted in FIG. 2A; and
b) detecting binding of the antibody to Tau polypeptide present in the sample.

### Claim 72 (depends on 71)

The method of claim 71, wherein the biological sample is blood, serum, plasma, urine, saliva, or cerebrospinal fluid.

### Claim 73 (depends on 71)

The method of claim 71, wherein the individual is suspected of having a tauopathy, has been diagnosed as having a tauopathy, or has a genetic predisposition to developing a tauopathy.

### Claim 74 (depends on 71)

The method of claim 71, wherein the method is quantitative.

### Claim 75 (depends on 71)

The method of claim 71, wherein the Tau polypeptide detected is total Tau polypeptide.

### Claim 76 (depends on 71)

The method of claim 71, wherein the Tau polypeptide detected is an N-terminal fragment of a full-length Tau polypeptide.

### Claim 77

A method of reducing the level of Aβ40 and/or Aβ42 in a neuronal cell and/or extracellular fluid in an individual, the method comprising administering to the individual:
a) an effective amount of an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41; or
b) a pharmaceutical composition comprising the antibody.

### Claim 78

(canceled)

### Claim 79

(canceled)

### Claim 80

A method of determining the amount of extracellular Tau (eTau) unbound to an anti-eTau antibody in a sample of cerebrospinal fluid (CSF) or interstitial fluid (ISF) obtained from a subject undergoing therapy with the anti-eTau antibody, the method comprising:
a) contacting an immobilized antibody with a sample of CSF or ISF obtained from the subject,
wherein the immobilized antibody comprises a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41, said contacting being under conditions suitable for binding of the unbound eTau to the immobilized antibody; and
b) determining the amount of eTau bound to the immobilized antibody, wherein the amount of eTau bound to the immobilized antibody is an indication of the amount of eTau unbound to the anti-Tau antibody in the sample.

### Claim 81 (depends on 80)

The method of claim 80, wherein the amount of eTau bound to the immobilized antibody is determined using a detectably labeled third antibody that does not compete with the immobilized antibody for binding to the eTau.

### Claim 82 (depends on 80)

The method of claim 80, wherein the sample is cerebrospinal fluid.

### Claim at position 22

-84. (canceled)

### Claim 85 (depends on 80)

The method of claim 80, comprising determining the level of total tau in the sample.

### Claim 86 (depends on 80)

The method of claim 80, comprising comparing the level of unbound Tau in the sample to the level of total tau in a CSF or ISF sample obtained from the individual before treatment with the anti-eTau antibody.

### Claim 87

(canceled)

### Claim 88 (depends on 86)

The method of claim 86, comprising adjusting the treatment regimen based on the compared level.

### Claim at position 27

-93. (canceled)

### Claim 94

A nucleic acid or nucleic acids encoding an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41.

### Claim 95 (depends on 94)

An expression vector or expression vectors comprising the nucleic acid or nucleic acids of claim 94.

### Claim 96 (depends on 95)

A host cell comprising the expression vector or expression vectors of claim 95.

### Claim 97 (depends on 96)

The host cell of claim 96, wherein the host cell is a HeLa cell, a CHO cell, a 293 cell, a Vero cell, a NIH3T3 cell, a CS cell, a HEK cell, or a BHK cell.