Binding domains of proteins of the repulsive guidance molecule (RGM) protein family and functional fragments thereof, and their use

• US 8,906,864 B2
• Filed: 09/29/2006
• Issued: 12/09/2014
• Est. Priority Date: 09/30/2005
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Inventors: Muller, Bernhard K., Schaffar, Gregor, Mueller, Reinhold
• Primary Examiner(s): Saoud, Christine J
• Assistant Examiner(s): LOCKARD, JON MCCLELLAND
• Application Number:
  US11/992,720
• Publication Number:
  US 20090297527A1
• Time in Patent Office: 2,993 Days
• Field of Search: None
• US Class Current: 514/21.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues

Abstract

The invention concerns the identification and use of neogenin receptor-binding domains of members of the repulsive guidance molecule (RGM) protein family as well as polypeptide fragments derived therefrom. The inventive domains, i.e. peptide fragments are suited as agents for the active or passive immunization of individuals as well as diagnostic and therapeutic agents for use with diseases or pathological conditions in whose origin or progression, a member of the RGM family and a cellular receptor assigned to this molecule are involved. The invention also concerns monoclonal and polyclonal antibodies directed against the inventive binding domains and against the polypeptides derived therefrom, and to method for producing the inventive domains, polypeptides and antibodies.

Claims

1. An isolated neogenin receptor-binding domain derived from a human RGM A as shown in SEQ ID NO:

2, comprising an amino acid sequence from amino acid position 200 to 350 as shown in SEQ ID NO;

2, or from amino acid position 200 to 325 as shown in SEQ ID NO;

2, or from amino acid position 200 to 300 as shown in SEQ ID NO;

2, or from amino acid position 200 to 285 as shown in SEQ ID NO;

2, or from amino acid position 250 to 285 as shown in SEQ ID NO;

2, or from amino acid position 260 to 285 as shown in SEQ ID NO;

2, or from amino acid position 215 to 340 as shown in SEQ ID NO;

2, or from amino acid position 260 to 340 as shown in SEQ ID NO;

2, or from amino acid position 250 to 300 as shown in SEQ ID NO;

2, or from amino acid position 260 to 291 as shown in SEQ ID NO;

2, or from amino acid position 210 to 260 as shown in SEQ ID NO;

2, or from amino acid position 290 to 350 as shown in SEQ ID NO;

2, or from amino acid position 218 to 284 as shown in SEQ ID NO;

2, or from amino acid position 266 to 335 as shown in SEQ ID NO;

2, or from amino acid position 168 to 422 as shown in SEQ ID NO;

2, or SEQ ID NO;

8, or SEQ ID NO;

26, or SEQ ID NO;

27, or a functional, neogenin receptor-binding fragment thereof.

2. An antigenic polypeptide fragment of the neogenin receptor-binding domain as claimed in claim 1.

3. The antigenic polypeptide fragment as claimed in claim 2, which comprises at least 10 consecutive amino acid residues of a peptide having one of the sequences as shown in SEQ ID NO:

8, SEQ ID NO;

26, SEQ ID NO;

27. amino acids 218-284 of SEQ ID NO;

2, amino acids 266-335 of SEQ ID NO;

2, or amino acids 168-422 of SEQ ID NO;

2.

4. A composition comprising a neogenin receptor-binding domain as claimed in claim 1 or an antigenic polypeptide fragment as claimed in claim 2, and a pharmaceutically acceptable carrier.

5. The composition as claimed in claim 4, formulated for intrathecal, intravenous, subcutaneous, parenteral, nasal or inhalational administration.

6. An isolated neogenin receptor-binding domain or binding fragment of SEQ ID NO:

2, which comprises at least 10 consecutive amino acid residues from the sequence region from position 260 to 291 or 267 to 285 as shown in SEQ ID NO;

2.