LINGO-2 antagonists for treatment of conditions involving motor neurons

• US 9,796,780 B2
• Filed: 05/14/2013
• Issued: 10/24/2017
• Est. Priority Date: 05/14/2012
• Status: Active Grant

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen MA Inc. (Biogen, Inc.)
• Inventors: Mi, Sha, Pepinsky, R. Blake
• Primary Examiner(s): Chernyshev, Olga N
• Application Number:
  US14/401,002
• Publication Number:
  US 20150118241A1
• Time in Patent Office: 1,624 Days
• Field of Search: None
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: 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
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4705 stimulating, promoting or activating activity
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides methods of treating diseases, disorders or injuries involving motor neuron survival and axonal growth, including amylotrophic lateral sclerosis, by the administration of a LINGO-2 antagonist. An exemplary method for promoting survival of a motor neuron, comprising contacting said motor neuron with an effective amount of a composition comprising a LINGO-2 antagonist selected from the group consisting of: (i) a soluble LINGO-2 polypeptide; (ii) a LINGO-2 antibody or antigen-binding fragment thereof; (iii) a LINGO-2 antagonist polynucleotide; (iv) a LINGO-2 aptamer; and (v) a combination of two or more of said LINGO-2 antagonists.

Claims

1. A method for promoting survival of a motor neuron, comprising contacting said motor neuron with an effective amount of a LINGO-2 antagonist, wherein the LINGO-2 antagonist is an antibody or antigen-binding fragment thereof that binds LINGO-2 but does not bind LINGO-1.

2. A method for promoting axonal growth of a motor neuron, comprising contacting said motor neuron with a LINGO-2 antagonist, wherein the LINGO-2 antagonist is an antibody or antigen-binding fragment thereof that binds LINGO-2 but does not bind LINGO-1.

3. A method for promoting survival of a motor neuron in a human subject in need thereof, comprising administering to the human subject an effective amount of a LINGO-2 antagonist, wherein the LINGO-2 antagonist is an antibody or antigen-binding fragment thereof that binds LINGO-2 but does not bind LINGO-1.

4. The method of claim 3 wherein said human subject has been diagnosed with a disease, disorder, or injury involving motor neurons.

5. A method for promoting axonal growth of a motor neuron in a human subject in need thereof, comprising administering to the human subject an effective amount of a LINGO-2 antagonist, wherein the LINGO-2 antagonist is an antibody or antigen-binding fragment thereof that binds LINGO-2 but does not bind LINGO-1.

6. A method for treating a disease, disorder, or injury associated with survival of a motor neuron in a human subject in need thereof comprising administering to the human subject a therapeutically effective amount of a composition comprising a LINGO-2 antagonist, wherein the LINGO-2 antagonist is an antibody or antigen-binding fragment thereof that binds LINGO-2 but does not bind LINGO-1.

7. The method of claim 6, wherein said disease, disorder, or injury is selected from the group consisting of amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), hereditary spastic paraparesis (HSP), X-linked spinobulbar muscular atrophy (SBMA;

Kenney disease), progressive bulbar palsy, pseudo-bulbar palsy, spinal muscular atrophy (SMA), post-polio syndrome (PPS), Huntington'"'"'s disease, Essential tremor (ET), motor neuron disease, paralysis, and Parkinson'"'"'s disease.

8. The method of claim 7, wherein said disease, disorder, or injury is amyotrophic lateral sclerosis (ALS).

9. A method for treating a disease, disorder, or injury associated with axonal growth of motor neurons in a human subject in need thereof comprising administering to the human subject a therapeutically effective amount of a composition comprising a LINGO-2 antagonist, wherein the LINGO-2 antagonist is an antibody or antigen-binding fragment thereof that binds LINGO-2 but does not bind LINGO-1.