US 9,803,012 B2Granted

Compositions and methods for regulating SAS1R

AssigneeUniversity of Virginia Patent Foundation

InventorsJohn C. Herr, Monika Sachdev, Arabinda Mandal

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Abstract

The present invention provides compositions and methods useful for regulating fertilization and for use as a contraceptive based on the discovery herein of an oocyte specific protein, SAS1R (Sperm Acrosomal SLLP1 Receptor), which is a sperm protein receptor. Six SAS1R variants, including the full length SAS1R, were identified. mSLLP1 and SAS1R co-localized to oocytes and to acrosomes of acrosome-reacted sperm. Interactions between mSLLP1 and SAS1R were demonstrated by far-western analysis, in a yeast two-hybrid system under stringent selection conditions, and by immunoprecipitation of SAS1R by anti-mSLLP1 as well as the converse. Purified recombinant SAS1R was found to have protease activity, to inhibit fertilization in-vitro, and to induce an immune response in females. Together, the results suggest SAS1R is a proteolytically active, oocyte and early embryo specific oolemmal metalloprotease receptor for the sperm intra-acrosomal ligand SLLP1 and is a target for regulating fertilization and as a contraceptive.

Claims4

Dependent claims

A method of identifying a compound which is an inhibitor of SAS1R, said method comprising:

(a) adding a test compound to a test sample comprising native SAS1R, wherein said test compound is an antibody that binds to amino acids selected from the group consisting of 26-50, 51-75, 76-100, 101-125, 126-150, 151-175 and 176-200 of SAS1R Variant 2 (SEQ ID NO:6);
selected from the group consisting of 26-50, 51-75, 76-100, 101-125, 136-150, 151-175 and 176-200 of SAS1R Variant I (SEQ ID NO:
19);
or selected from the group consisting of 26-50, 51-75, 76-100, 100-125, 126-150, 151-175 and 176-200 of SAS1R Variant I (SEQ ID NO:23);
(b) analyzing the level of SAS1R activity or expression in said test sample with the level of SAS1R activity or expression in an otherwise identical sample comprising SAS1R not subjected to a test compound;
(c) wherein a lower level of SAS1R activity or expression in said test sample subjected to a test compound compared with the level of SAS1R activity or expression in said otherwise identical sample is an indication that said test compound is an inhibitor of SAS1R;
and
(d) thereby identifying a compound which is an inhibitor of SAS1R.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/479,167Filed 23 May 2012 · division
Priority: 23 Feb 2005
Published: US 2012/0252031 A14 Oct 2012
Granted: 31 Oct 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
A61K 38/1709
From vertebrates: from mammals
A61K 38/177
From animals; from humans: receptors; Cell surface antigens; Cell surface determinants
A61K 38/4886
Acting on peptide bonds: metalloendopeptidases , e.g. collagenase

Family

Application60/655,562Us provisional application · filed 23 Feb 2005
Application60/689,181Us provisional application · filed 10 Jun 2005
PCT/US2006/005970Parent of this continuation-in-part · filed 21 Feb 2006
Application61/111,903Us provisional application · filed 6 Nov 2008
Application61/225,790Us provisional application · filed 15 Jul 2009
Application61/243,411Us provisional application · filed 17 Sep 2009
Application61/244,543Us provisional application · filed 22 Sep 2009
Application12/613,947Parent of this division · filed 6 Nov 2009
US 2012/0252031 A1Pre-grant publication · published 4 Oct 2012
Application11/915,225Parent of this continuation-in-part
Application12/613,947Parent of this continuation-in-part
US 2009/0214552 A1Published application
US 2010/0183617 A1Published application
US 9,803,012 B2This patent

From the US filing history. Foreign family members aren’t listed.