Mutated ACVR1 for diagnosis and treatment of Fibrodyplasia Ossificans Progressiva (FOP)

• US 8,895,711 B2
• Filed: 04/17/2007
• Issued: 11/25/2014
• Est. Priority Date: 04/18/2006
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Kaplan, Frederick S., Shore, Eileen M.
• Primary Examiner(s): KAPUSHOC, STEPHEN THOMAS
• Application Number:
  US12/296,275
• Publication Number:
  US 20090253132A1
• Time in Patent Office: 2,779 Days
• Field of Search: None
• US Class Current: 536/23.1
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0306 Animal model for genetic diseases
• CPC Class Codes: A01K 2267/0331 Animal model for proliferative diseases
• CPC Class Codes: A01K 67/0275 Genetically modified vertebrates, e.g. transgenic
• 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: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 14/4713 Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/91205 Phosphotransferases in general
• CPC Class Codes: G01N 2800/10 Musculoskeletal or connective tissue disorders
• CPC Class Codes: G01N 2800/2842 Pain, e.g. neuropathic pain, psychogenic pain
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere

Abstract

This invention is directed to mutated Activin A type I receptor proteins (ACVR1) and isolated nucleic acids encoding same. The invention also relates to the use of mutated ACVR1 in the diagnosis and treatment of Fibrodysplasia Ossificans Progressiva (FOP).

Claims

1. A molecular beacon nucleic acid comprising a stem and a loop and a detectable label, wherein the loop consists of at least 15 contiguous bases of SEQ ID NO:

34 or of at least 15 contiguous bases of the complement of SEQ ID NO;

34, wherein position 11 of SEQ ID NO;

34 is an A.

2. A method of diagnosing Fibrodysplasia Ossificans Progressiva (FOP) in a human subject, said method comprising:

contacting a biological sample containing ACVR1 nucleic acids from said subject with the molecular beacon of claim 1;

detecting the presence of an ACVR1 nucleic acid that encodes histidine at the position corresponding to position 206 of SEQ ID NO;

21; and

correlating the presence of an ACVR1 nucleic acid that encodes histidine at the position corresponding to position 206 of SEQ ID NO;

21 with a diagnosis of FOP in the subject.

3. The method of claim 2 wherein the FOP is inherited FOP.

4. The method of claim 2 wherein the FOP is sporadic FOP.

5. The method of claim 2, wherein the molecular beacon has a photoluminescent dye at on one of the 5′

or 3′

ends and a quenching agent at the opposite 3′

or 5′

end.

6. The method of claim 2, further comprising a step wherein ACVR1 nucleic acids from the subject are amplified.

7. A kit for diagnosing FOP in a subject, said kit comprising the molecular beacon of claim 1.

8. A method of diagnosing Fibrodysplasia Ossificans Progressiva (FOP) in a human subject, said method comprising:

amplifying by PCR ACVR1 nucleic acids in a biological sample from said subject;

contacting the amplified ACVR1 nucleic acids with the molecular beacon of claim 1;

detecting the presence of an ACVR1 nucleic acid that encodes histidine at the position corresponding to position 206 of SEQ ID NO;

21; and

correlating the presence of an ACVR1 nucleic acid that encodes histidine at the position corresponding to position 206 of SEQ ID NO;

21 with a diagnosis of FOP in the subject.

9. The method of claim 8 wherein the FOP is inherited FOP.

10. The method of claim 8 wherein the FOP is sporadic FOP.

11. The method of claim 8, wherein the molecular beacon has a photoluminescent dye at on one of the 5′

or 3′

ends and a quenching agent at the opposite 3′

or 5′

end.