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Government-Owned Inventions; Availability for Licensing

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AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

SUMMARY:

The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.

ADDRESSES:

Licensing information and copies of the U.S. patent applications listed below may be obtained by writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

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SUPPLEMENTARY INFORMATION:

Antibodies and Antisera Recognizing Members of the ArfGap Family of Proteins

Description of Technology

The technology involves antibodies and antisera that recognize members of the ArfGap protein family, including the following proteins:

  • ACAP1, which is related to ASAP1, a putative oncogene that regulates cancer cell invasion into normal tissues. ACAP1 regulates integrins, which are critical for cell movement associated with cancer cell invasion and is a target of the oncogene Akt.
  • ACAP2, which is related to ASAP1, a putative oncogene that regulates cancer cell invasion into normal tissues.
  • AGAP2 (also known as PIKE-A), ASAP1 (also called AMAP1 and DDEFl), and ASAP3 all exhibit elevated expression levels in cancer cells compared to non-transformed cells and as putative oncogenes have been implicated as regulators of cancer cell invasion into normal tissues and contributors to brain, eye and breast, and liver cancers, respectively.
  • ARAP1 (also called Centaurin Delta 2), which has been implicated as a regulator of epidermal growth factor receptor, which plays important roles in several malignancies.
  • ARAP2 (also called Centaurin Delta 1), GIT1 and GIT2; all three of which have been implicated as regulators of cell migration required for cancer cell invasion into normal tissues and metastasis.
  • ARAP3, a target of the Src oncogene, has been implicated as a regulator of cell movement and signaling.
  • ArfGAP1, which is critical to cell function, including protein trafficking.
  • ASAP2 (also known as PAG3 or as Pap in the 1999 Molecular and Cellular Biology publication), is highly related to ASAP1, which has been implicated as a regulator of cancer cell invasion into normal tissues.

The table below summarizes the antibodies and antisera available against different ArfGap proteins. Each material has been raised or generated to the peptide sequence listed.

Antibodies and Antisera Recognizing ArfGap Proteins

ArfGap memberAntibody/serum ID (Alt. Name)Antibody sourcePeptide sequence (ID)HHS Ref. No.
ACAP11241 (Arf6-specific GAP)RabbitRPRGQPPVPPKPSIR(556)E-244-2008/0
ACAP21288RabbitREKGDESEKLDKKSS(365)E-242-2008/0
AGAP24569, 4571RabbitERVDDPELQDSI and PLSREPPPSPMVKKQ  (483)E-222-2008/0
ARAP11153RabbitSLIPLRGSENEMRRSVE-220-2008/0
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ARAP21185, 1187RabbitRSRTLPKELQDEQILK  (1689) and ANVHKTKKNDDPSKDYE-220-2008/1
ARAP3862, 863, 864, 865 (CENTD3/DRAG1)RabbitDKDPPFPKGVIPLTAIE and EPVYEEPVYEEVGAFPEE-220-2008/2
ArfGAP1870RabbitEWSLESSPAQNWTPPQP  (123)E-243-2008/0
ASAP1642, 645, 551, 553RabbitVELAPKPQVGELPPKPG (962), DQDRTALQKVKKSVAC, and murine protein residues 325-725; 440-724E-221-2008/0
ASAP1a574RabbitLSKKPPPPPPGHKRTL  (837)E-221-2008/0
ASAP1MouseVELAPKPQVGELPPKPG  (962)E-252-2008/0
ASAP21267, 4574, 4575, 578RabbitDEKLQPSPNRREDRP(706) and human protein fragment of the PH, Arf GAP and Ankyrin repeat domainsE-221-2008/1
ASAP3Anti-ASAP3 (DDEFL1/UPLC1/ACAP4)RabbitWVISTEPGSDSEEDEEKRE-221-2008/2
GIT1RabbitLRQPPGPVPTPPLPSER and RKTVPPEPGAPVDFE-245-2008/0
GIT2RabbitRSSEVCADCSGPDPS and KVNNNLSDELRIMQKKE-245-2008/1

Applications

  • Immunoblotting and other procedures to identify the ArfGap proteins in cells and tissues;
  • Identifying tumors, such as those found in brain, breast, eye and liver cancers, based on protein expression levels;
  • Examining the invasive behavior of tumor cells.

Development Status

The antibodies and antisera have been raised or generated to the particular peptide sequence given in the table above. These are available as Research Tools.

Inventors

Paul A. Randazzo et al. (NCI).

Relevant Publications

These antibodies and antisera are further described in the following research articles:

1. Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J. Identification of a new Pyk2 target protein with Arf-GAP activity. Mol Cell Biol. 1999 Mar;19(3):2338-2350.

2. Bharti S, Inoue H, Bharti K, Hirsch DS, Nie Z, Yoon HY, Artym V, Yamada KM, Mueller SC, Barr VA, Randazzo PA. Src-dependent phosphorylation of ASAP1 regulates podosomes. Mol Cell Biol. 2007 Dec;27(23):8271-8283.

3. Dai J, Li J, Bos E, Porcionatto M, Premont RT, Bourgoin S, Peters PJ, Hsu VW. ACAP1 promotes endocytic recycling by recognizing recycling sorting signals. Dev Cell. 2004 Nov;7(5):771-776.

4. Ha VL et al. ASAP3 is a focal adhesion-associated Arf GAP that functions in cell migration and invasion. J Biol Chem. 2008 May 30;283(22):14915-14926.

5. I ST, Nie Z, Stewart A, Najdovska M, Hall NE, He H, Randazzo PA, Lock P. ARAP3 is transiently tyrosine phosphorylated in cells attaching to fibronectin and inhibits cell spreading in a RhoGAP-dependent manner. J Cell Sci. 2004 Dec 1;117(Pt 25):6071-6084.

6. Inoue H and Randazzo PA. Arf GAPs and their interacting proteins. Traffic 2007 Nov;8(11):1465-1475.

7. Li J, Ballif BA, Powelka AM, Dai J, Gygi SP, Hsu VW. Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration. Dev Cell. 2005 Nov;9(5):663-673.

8. Miura K, Jacques KM, Stauffer S, Kubosaki A, Zhu K, Hirsch DS, Resau J, Zheng Y, Randazzo PA. ARAP1: a point of convergence for Arf and Rho signaling. Mol Cell 2002 Jan;9(1):109-119.

9. Nie Z, Fei J, Premont RT, Randazzo PA. The Arf GAPs AGAP1 and AGAP2 distinguish between the adaptor protein complexes AP-1 and AP-3. J Cell Sci. 2005 Aug 1;118(Pt 15):3555-3566.

10. Randazzo PA, Andrade J, Miura K, Brown MT, Long YQ, Stauffer S, Roller P, Cooper JA. The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton. Proc Natl Acad Sci USA. 2000 Apr 11;97(8):4011-4016.

11. Liu W, Duden R, Phair RD, Lippincott-Schwartz J. ArfGAP1 dynamics and its role in COPI coat assembly on Golgi membranes of living cells. J. Cell Biol. 2005 Mar 28;168(7):1053-1063.

12. Yoon MY, Miura K, Cuthbert EJ, Davis KK, Ahvazi B, Casanova JE, Randazzo PA. ARAP2 effects on the actin cytoskeleton are dependent on Arf6-specific GTPase-activating-protein activity and binding to RhoA-GTP. J Cell Sci. 2006 Nov 15;119(Pt 22):4650-4666.

Patent Status

Patent protection is not being pursued for this technology.

  • HHS Reference No. E-220-2008/0—Research Tool.
  • HHS Reference No. E-220-2008/1—Research Tool.
  • HHS Reference No. E-220-2008/2—Research Tool.
  • HHS Reference No. E-221-2008/0—Research Tool.
  • HHS Reference No. E-221-2008/1—Research Tool.
  • HHS Reference No. E-221-2008/2—Research Tool.
  • HHS Reference No. E-222-2008/0—Research Tool.
  • HHS Reference No. E-242-2008/0—Research Tool.
  • HHS Reference No. E-243-2008/0—Research Tool.
  • HHS Reference No. E-244-2008/0—Research Tool.
  • HHS Reference No. E-245-2008/0—Research Tool.
  • HHS Reference No. E-245-2008/1—Research Tool.
  • HHS Reference No. E-252-2008/0—Research Tool.

Licensing Status

Available for non-exclusive biological materials licensing only.Start Printed Page 45231

Licensing Contact

Surekha Vathyam, Ph.D.; 301-435-4076; vathyams@mail.nih.gov.

Start Signature

Dated: July 28, 2008.

Richard U. Rodriguez,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.

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[FR Doc. E8-17812 Filed 8-1-08; 8:45 am]

BILLING CODE 4140-01-P