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US 2019/0169274 A1Published application
Human anti-tau antibodies
AssigneesBiogen MA Inc., Biogen International Neuroscience GmbH
InventorsPaul H. Weinreb, Feng Chen, Ellen A. Garber Stark, Jan Grimm, Fabio Montrasio
Life of this patent
Estimating the term…
Abstract
Provided are novel human tau-specific antibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for tau are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for tau targeted immunotherapy and diagnosis, respectively.
Claims33
-42. (canceled)
A polynucleotide linked to a heterologous nucleic acid, wherein the polynucleotide is selected from the group consisting of:
- (a) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:79, 80, and 81, respectively, wherein the VH when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:46 binds to tau;
- (b) a polynucleotide encoding an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:82, 83, and 84, respectively, wherein the VL when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:45 binds to tau;
- (c) a polynucleotide encoding (i) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising CDRs 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:79, 80, and 81, respectively;
- and (ii) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:82, 83, and 84, respectively, wherein the VH when paired with the VL binds to tau;
- (d) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising the amino acid sequence set forth in SEQ ID NO:45, wherein the VH when paired with a VL comprising the amino acid sequence set forth in SEQ ID NO:46 binds to tau;
- (e) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising the amino acid sequence set forth in SEQ ID NO:45, wherein the VH when paired with a VL comprising the amino acid sequence set forth in SEQ ID NO:221 binds to tau;
- (f) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising the amino acid sequence set forth in SEQ ID NO:45, wherein the VH when paired with a VL comprising the amino acid sequence set forth in SEQ ID NO:222 binds to tau;
- (g) a polynucleotide encoding an immunoglobulin light chain or a fragment thereof comprising a VL comprising the amino acid sequence set forth in SEQ ID NO:46, wherein the VL when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:45 binds to tau;
- (h) a polynucleotide encoding an immunoglobulin light chain or a fragment thereof comprising a VL comprising the amino acid sequence set forth in SEQ ID NO:221, wherein the VL when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:45 binds to tau;
- (i) a polynucleotide encoding an immunoglobulin light chain or a fragment thereof comprising a VL comprising the amino acid sequence set forth in SEQ ID NO:222, wherein the VL when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:45 binds to tau;
- (j) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising the amino acid sequence set forth in SEQ ID NO:45 and an immunoglobulin light chain or a fragment thereof comprising a VL comprising the amino acid sequence set forth in SEQ ID NO:46;
- (k) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising the amino acid sequence set forth in SEQ ID NO:45 and an immunoglobulin light chain or a fragment thereof comprising a VL comprising the amino acid sequence set forth in SEQ ID NO:221;
- (l) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising the amino acid sequence set forth in SEQ ID NO:45 and an immunoglobulin light chain or a fragment thereof comprising a VL comprising the amino acid sequence set forth in SEQ ID NO:222;
- (m) a polynucleotide encoding an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:91, 92, and 93, respectively, wherein the VH when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:46 binds to tau;
- (n) a polynucleotide encoding an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:94, 95, and 96, respectively, wherein the VL when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:45 binds to tau;
- and
- (o) a polynucleotide encoding (i) an immunoglobulin heavy chain or a fragment thereof comprising a VH comprising CDRs 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:91, 92, and 93, respectively;
- and (ii) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:
- 94, 95, and 96, respectively, wherein the VH when paired with the VL binds to tau.
16 more elements
A cDNA comprising a polynucleotide encoding a polypeptide comprising any one of:
- (a) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:79, 80, and 81, respectively, wherein the VH when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:46 binds to tau;
- or
- (b) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:82, 83, and 84, respectively, wherein the VL when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:45 binds to tau.
An expression vector comprising a heterologous promoter operably linked to a polynucleotide encoding a polypeptide comprising:
- (a) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:79, 80, and 81, respectively, wherein the VH when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:46 binds to tau;
- or
- (b) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 with the amino acid sequences set forth in SEQ ID NOs:82, 83, and 84, respectively, wherein the VL when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO:45 binds to tau.
A method of treating a neurodegenerative tauopathy in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of an anti-tau antibody or tau-binding fragment thereof, wherein the anti-tau antibody or tau-binding fragment thereof comprises:
- a VH comprising VH complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:
- 44 or 45;
- and
- a VL comprising VL complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:46, 221, or 222.
1 more element
A method of treating abnormal accumulation or deposition of tau in the central nervous system in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of an anti-tau antibody or tau-binding fragment thereof, wherein the anti-tau antibody or tau-binding fragment thereof comprises:
- a VH comprising VH complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:
- 44 or 45;
- and
- a VL comprising VL complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:46, 221, or 222.
1 more element
A method for in vivo detection of tau deposition in the brain, the method comprising:
- administering to a human subject an antibody or antigen-binding fragment thereof that specifically binds to tau, wherein the antibody or antigen-binding fragment thereof comprises:
- a VH comprising VH complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:
- 44 or 45;
- and a VL comprising VL complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:46, 221, or 222, wherein the antibody or antigen-binding fragment thereof is attached to a detectable label;
- and
- detecting the detectable label in the brain of the human subject, to thereby detect tau deposition in the brain of the human subject.
3 more elements
A method of diagnosing or monitoring the progression of a neurodegenerative tauopathy, the method comprising:
- measuring the level of pathologically modified or aggregated tau in a sample from a human subject with an anti-tau antibody or tau-binding fragment thereof, wherein the anti-tau antibody or tau-binding fragment thereof comprises a VH comprising VH complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:
- 44 or 45;
- and a VL comprising VL complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:46, 221, or 222;
- and
- comparing the level of modified or aggregated tau to a reference standard that indicates the level of the pathologically modified or aggregated tau in one or more control subjects,
- wherein a difference or similarity between the level of pathologically modified or aggregated tau and the reference standard indicates that the human subject has a neurodegenerative tauopathy.
3 more elements
An antibody or antigen-binding fragment thereof that binds to human tau and comprises:
- a VH comprising VH complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:
- 44 or 45;
- and a VL comprising VL complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:46, 221, or 222,
- wherein the antibody or antigen-binding fragment thereof comprises polyethylene glycol or a detectable label selected from the group consisting of an enzyme, a radioisotope, a fluorescent compound, a chemiluminescent compound, a bioluminescent compound, and a heavy metal.
1 more element
An anti-tau single chain antibody or scFv antibody comprising:
- a VH comprising VH complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:
- 44 or 45;
- and
- a VL comprising VL complementarity determining regions 1, 2, and 3 of the amino acid sequences set forth in any one of SEQ ID NO:46, 221, or 222.
1 more element
Dependencies are inferred from the claim text.