[Federal Register Volume 73, Number 150 (Monday, August 4, 2008)]
[Notices]
[Pages 45229-45231]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-17812]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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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.

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
----------------------------------------------------------------------------------------------------------------
                          Antibody/serum ID
     ArfGap member           (Alt. Name)          Antibody source       Peptide sequence (ID)      HHS Ref. No.
----------------------------------------------------------------------------------------------------------------
ACAP1.................  1241 (Arf6-specific    Rabbit...............  RPRGQPPVPPKPSIR(556).....     E-244-2008/0
                         GAP).
ACAP2.................  1288.................  Rabbit...............  REKGDESEKLDKKSS(365).....     E-242-2008/0
AGAP2.................  4569, 4571...........  Rabbit...............  ERVDDPELQDSI and              E-222-2008/0
                                                                       PLSREPPPSPMVKKQ.
                                                                       (483)...................
ARAP1.................  1153.................  Rabbit...............  SLIPLRGSENEMRRSV.........     E-220-2008/0

[[Page 45230]]

 
ARAP2.................  1185, 1187...........  Rabbit...............  RSRTLPKELQDEQILK.........     E-220-2008/1
                                                                       (1689) and
                                                                       ANVHKTKKNDDPSKDY.
ARAP3.................  862, 863, 864, 865     Rabbit...............  DKDPPFPKGVIPLTAIE and         E-220-2008/2
                         (CENTD3/DRAG1).                               EPVYEEPVYEEVGAFPE.
ArfGAP1...............  870..................  Rabbit...............  EWSLESSPAQNWTPPQP........     E-243-2008/0
                                                                       (123)...................
ASAP1.................  642, 645, 551, 553...  Rabbit...............  VELAPKPQVGELPPKPG (962),      E-221-2008/0
                                                                       DQDRTALQKVKKSVAC, and
                                                                       murine protein residues
                                                                       325-725; 440-724.
ASAP1a................  574..................  Rabbit...............  LSKKPPPPPPGHKRTL.........     E-221-2008/0
                                                                       (837)...................
ASAP1.................  .....................  Mouse................  VELAPKPQVGELPPKPG........     E-252-2008/0
                                                                       (962)...................
ASAP2.................  1267, 4574, 4575, 578  Rabbit...............  DEKLQPSPNRREDRP(706) and      E-221-2008/1
                                                                       human protein fragment
                                                                       of the PH, Arf GAP and
                                                                       Ankyrin repeat domains.
ASAP3.................  Anti-ASAP3 (DDEFL1/    Rabbit...............  WVISTEPGSDSEEDEEKR.......     E-221-2008/2
                         UPLC1/ACAP4).
GIT1..................  .....................  Rabbit...............  LRQPPGPVPTPPLPSER and         E-245-2008/0
                                                                       RKTVPPEPGAPVDF.
GIT2..................  .....................  Rabbit...............  RSSEVCADCSGPDPS and           E-245-2008/1
                                                                       KVNNNLSDELRIMQKK.
----------------------------------------------------------------------------------------------------------------

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.

[[Page 45231]]

Licensing Contact

    Surekha Vathyam, Ph.D.; 301-435-4076; [email protected].

    Dated: July 28, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-17812 Filed 8-1-08; 8:45 am]
BILLING CODE 4140-01-P