# US 6,723,698 B2 · Methods and compositions for the treatment of motor neuron injury and neuropathy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,723,698 B2 - Document ID: US6723698B2 - Status: Granted - Kind: B2 - Application number: 08/937,755 - Filed: 1997-09-25 - Published: 2002-04-25 - Granted: 2004-04-20 - Earliest claimed: 1991-03-11 - Assignees: Curis, Inc. - Inventors: David C. Rueger; Kuber T. Sampath; Hermann Oppermann; Roy H. L. Pang; Charles M. Cohen - Web page: https://patentgrep.com/patent/US6723698B2 ## CPC - A01N 1/10: Preservation of living parts - A01N 1/126: Physiologically active agents, e.g. antioxidants or nutrients - A01N 1/12: Chemical aspects of preservation - A61K 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)} - A61K 38/1703: {from vertebrates} - A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor} - A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24} - A61L 27/24: Collagen - C07K 14/495: Transforming growth factor [TGF] - C07K 14/51: Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor - C07K 16/22: against growth factors {; against growth regulators} - A61F 2310/00365: Proteins; Polypeptides; Degradation products thereof - G01N 2500/10: involving cells - A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS - 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) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - 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) - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - 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 Disclosed are therapeutic treatment methods, compositions and devices for maintaining neural pathways in a mammal, including enhancing survival of neurons at risk of dying, inducing cellular repair of damaged neurons and neural pathways, and stimulating neurons to maintain their differentiated phenotype. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration. ## Claims ### Claim 1 A method of treating a mammal with symptoms of amyotrophic lateral sclerosis (ALS), comprising administering to said mammal a morphogen, wherein the morphogen: (1) comprises a dimeric protein having an amino acid sequence with: (a) at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2; or, (b) greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1; and (2) stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro; whereby motor function is improved in said mammal. ### Claim 2 A method of treating a mammal with symptoms of spinal cord injury, comprising administering to said mammal a morphogen, wherein the morphogen: (1) comprises a dimeric protein having an amino acid sequence with: (a) at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO; 2; or, (b) greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1; and (2) stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro; whereby motor function is improved in said mammal. ### Claim 3 (depends on 2) The method of claim 2, wherein said spinal cord injury results from a mechanical trauma. ### Claim 4 (depends on 2) The method of claim 2, wherein said spinal cord injury results from a tumor. ### Claim 5 (depends on 2) The method of claim 2, wherein said spinal cord injury results from a chemical trauma. ### Claim 6 A method of improving motor function in a mammal with symptoms of amyotrophic lateral sclerosis, comprising administering to the mammal a morphogen, wherein the morphogen: (1) comprises a dimeric protein having an amino acid sequence with: (a) at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2; or, (b) greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1; and (2) stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro; whereby motor function is improved in the mammal. ### Claim 7 A method of improving motor function in a mammal with symptoms of spinal cord injury, comprising administering to the mammal a morphogen, wherein the morphogen: (1) comprises a dimeric protein having an amino acid sequence with: (a) at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2; or, (b) greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1; and (2) stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro; whereby motor function is improved in the mammal. ### Claim 8 A method of treating a mammal with symptoms of amyotrophic lateral sclerosis, comprising administering to said minimal a morphogen, selected from: human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, DMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, or BMP6, whereby motor function is improved in said mammal. ### Claim 9 A method of treating a mammal with symptoms of spinal cord injury, comprising administering to said mammal a morphogen selected from: human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, or BMP6, whereby motor function is improved in said mammal. ### Claim 10 A method of improving motor function in a mammal with symptoms of amyotrophic lateral sclerosis, comprising administering to the mammal a morphogen selected from: human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, or BMP6, whereby the motor function is improved in said mammal. ### Claim 11 A method of improving motor function in a mammal with symptoms of spinal cord injury, comprising administering to the mammal a morphogen selected from: human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, or BMP6, whereby the motor function is improved in said mammal. ### Claim 12 (depends on 1, 2, 6, 7, 8, 9, 10) The method of any one of claims 1, 2, 6, 7, 8, 9, 10, or 11, wherein said morphogen is complexed with at least one pro-domain polypeptide of the pro-domains of: OP-1, OP-2, 60A, GDF-1, BMP-2A, BMP-2B, DPP, Vg1, Vgr-1, BMP-3, BMP5, or BMP6. ### Claim 13 (depends on 12) The method of claim 12, wherein said morphogen is complexed with a pair of said pro-domain polypeptides. ### Claim 14 A method of repairing damaged neural pathway of the peripheral nervous system (PNS) of a mammal, comprising administering to said mammal a morphogen, wherein the morphogen: (1) comprises a dimeric protein having an amino acid sequence with: (a) at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2; or, (b) greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1; and, (2) stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro; whereby the damaged neural pathway of the PNS in said mammal are repaired. ### Claim 15 A method of improving motor function in a mammal with symptoms of neural pathway damage in the peripheral nervous system (PNS), comprising administering to said mammal a morphogen, wherein the morphogen: (1) comprises a dimeric protein having an amino acid sequence with: (a) at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2; or, (b) greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1; and, (2) stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro; whereby motor function is improved in said mammal. ### Claim 16 (depends on 1, 2, 6, 7, 14) A method of claim 1, 2, 6, 7, 14, or 15, wherein the morphogen is OP-1.