Baylor College of Medicine

Washington University

Dana-Farber-Cancer Institute Inc.

Research Development Foundation

Wyeth

Baylor University

Metamorphix, Inc.

Martin Matthew Matzuk

Irving Boime

Pei Wang

Jeffrey L Keene

Jun Qi

Lutfi Abu-Elheiga

Salih J Wakil

Julia Andrea Elvin

James Elliott Bradner

James Bradner

Yong Wang

Nicholas Simmons

Wei Yan

Zhuang Jin

Timothy Palzkill

Doris Taylor

Yuchen Bai

John Faver

Justin Anglin

The disclosure relates, in certain aspects, to compounds that can be used to inhibit β-lactamases, such as but not limited to OXA enzymes, such as but not limited to OXA-24, OXA-48, and/or OXA-58. In certain embodiments, these compounds can be used to inhibit activity of β-lactamases in vitro and in vivo.

Compounds and methods for treating or preventing bacterial infections

The invention relates to compositions and methods for effecting male contraception.

Male contraceptive compositions and methods of use

Ovary specific proteins O1 180, O1 184 and O1 236, polynucleotides encoding them, antibodies which are immunoreactive with them and vectors and host cells containing O1 180, O1 184 or O1 236 are provided. Also provided are methods for detecting cell proliferative or degenerative disorders of ovarian origin and which are associated with O1 180, O1 184 or O1 236. Further provided are methods for the evaluation of potential contraceptives using the proteins of the invention, as well as methods for the screening for genetic mutations in signaling pathways that are associated with some forms of human infertility or gynecological cancers, also using the proteins/mRNAs/genes of the invention. The proteins/mRNAs/genes of the invention may also be used as markers for identifying primary and metastatic neoplasms of ovarian origin and as indicators of developmental anomalies in prenatal screening procedures. Furthermore, assays of the proteins/mRNAs/genes of the invention can be used in diagnostic assays for detecting forms of infertility and other diseases, including germ cell tumors and polycystic ovary syndrome. The proteins of the invention may be useful targets for in vitro fertilization procedures or in enhancing the number of eggs that can be retrieved from the human donor, e.g., in enhancing the success rate.

Ovary-specific genes and proteins

The present invention relates to compositions and methods for modulating conception in animals. More particularly, the composition modulates mRNA degradation during gametogenesis and early development. Yet further, the present invention relates to pharmaceutical compositions and methods for modulating diseases of the reproductive organs, such as hyperproliferative diseases.

Identification of oligoadenylate synthetase-like genes

Isolated GDF-9 regulatory sequences are disclosed, as well as methods of using the sequences to modulate tissue-specific expression of genes. The GDF-9 regulatory sequences include, for example, enhancer and promoter elements that naturally drive transcription of GDF-9 in specific tissues. The GDF-9 regulatory sequences can be derived from the untranscribed upstream (e.g., first 10 kilobases) and downstream regions, and transcribed, untranslated regions of a GDF-9 gene.

Growth differentiation factor-9 regulatory sequences and uses therefor

Ovary-specific proteins O1-180, O1-184 and O1-236, polynucleotides encoding them, antibodies which are immunoreactive with them and vectors and host cells containing O1-180, O1-184 or O1-236 are provided. Also provided are methods for detecting cell proliferative or degenerative disorders of ovarian origin and which are associated with O1-180, O1-184 or O1-236. Further provided are methods for the evaluation of potential contraceptives using the proteins of the invention, as well as methods for the screening for genetic mutations in signaling pathways that are associated with some forms of human infertility or gynecological cancers, also using the proteins/mRNAs/genes of the invention. The proteins/mRNAs/genes of the invention may also be used as markers for identifying primary and metastatic neoplasms of ovarian origin and as indicators of developmental anomalies in prenatal screening procedures. Furthermore, assays of the proteins/mRNAs/genes of the invention can be used in diagnostic assays for detecting forms of infertility and other diseases, including germ cell tumors and polycystic ovary syndrome. The proteins of the invention may be useful targets for in vitro fertilization procedures or in enhancing the number of eggs that can be retrieved from the human donor, e.g., in enhancing the success rate.

The invention provides recombinant native and mutein forms of human follicle stimulating hormone beta subunit (FSH beta) with characteristic glycosylation patterns which are influential in the metabolic activity of the protein. The invention also provides recombinant mutant forms of the human alpha subunit common to FSH, LH, CG, and TSH, to obtain hormones which also have unique glycosylation patterns. Also provided are recombinant materials to produce these subunits separately or together to obtain complete heterodimeric hormones of regulated glycosylation pattern.

Follicle stimulating hormone-glycosylation analogs

The present invention highlights the role of acetyl-CoA carboxylase through its product malonyl-CoA in regulating fatty acid oxidation and synthesis, glucose metabolism and energy homeostasis. It discloses transgenic mice with inactivating mutations in the endogenous gene for the acetyl-CoA carboxylase 2 isoform of acetyl-CoA carboxylase. Inactivation of acetyl-CoA carboxylase 2 results in mice exhibiting a phenotype of reduced malonyl-CoA levels in skeletal muscle and heart, unrestricted fat oxidation, and reduced fat accumulation in the liver and fat storage cells. As a result, the mice consume more food but accumulate less fat and remain leaner than wild-type mice fed the same diet. The instant invention provides a useful animal model to regulate malonyl-CoA production by ACC2 in the regulation of fatty acid oxidation by muscle, heart, liver and other tissues. They also identify potential inhibitors for studying the mechanisms of fat metabolism and weight control.

Acetyl-coenzyme A carboxylase 2 as a target in the regulation of fat burning, fat accumulation, energy homeostasis and insulin action

The present invention relates to a method of identifying an agent which alters (inhibits, enhances) activity of GDF-9. The method involves combining cells having a receptor for GDF-9 and a gene, wherein expression of the gene is regulated by binding of GDF-9 to the receptor; GDF-9; and an agent to be assessed. The combination produced is maintained under conditions appropriate for binding of GDF-9 to the receptors on the cells. The extent to which binding of GDF-9 to the receptors on the cells occurs is then determined, wherein binding of GDF-9 to the receptor to a lesser or greater extent in the presence of the agent to be assessed than in its absence, is indicative of an agent which alters GDF-9 activity.

Assay for growth differentiation factor 9

The present invention discloses transgenic mice with inactivating mutations in the endogenous gene for the acetyl-CoA carboxylase-2 isoform of acetyl-CoA carboxylase. Inactivation of acetyl-CoA carboxylase-2 results in mice exhibiting a phenotype of reduced malonyl-CoA levels in skeletal muscle and heart, unrestricted fat oxidation, and reduced fat accumulation in the liver and fat storage cells. As a result, the mice consume more food but accumulate less fat and remain leaner than wild type mice fed the same diet. These results demonstrate that inhibition of ACC2 acetyl-CoA carboxylase could be used to regulate fat oxidation and accumulation for purposes of weight control. The transgenic mice of the instant invention provide a useful animal model to identify such inhibitors and for studying the mechanisms of fat metabolism and weight control.

ACC2-knockout mice and uses thereof

Recombinant materials are provided for the production of the &agr;-glycoprotein hormone subunit. These muteins have utility as antagonists and in altering pharmacokinetic activity of these hormones.

Modified protein pharmaceuticals extended with a CTP unit retain their biological activity and they had extended biological half-lives. The CTP extension represents an amino acid sequence derived from that of positions 112-118 to 145 of human chorionic gonadotropin.

Carboxy terminal peptide-extended proteins

Expression constructs for the alpha subunit common to the four human reproductive hormones are disclosed which have enhanced efficiency. These constructs are characterized by the presence of only one intron interrupting the coding sequence for the alpha subunit.

DNA encoding reproductive hormones and expression using a minigene

The invention provides recombinant native and mutein forms of human reproductive hormones with characteristic glycosylation patterns which are influential in the metabolic activity of the protein. The invention also provides recombinant mutant forms of the human alpha subunit common to FSH, LH, CG, and TSH, to obtain hormones which also have unique glycosylation patterns. Also provided are recombinant materials to produce these subunits separately or together to obtain complete heterodimeric hormones of regulated glycosylation pattern and activity. Modified forms of LH and FSH beta subunits which enhance the rate of dimerization and secretion of the dimers or individual chains are also disclosed.

Growing community of inventors

Pearland, TX, United States of America

Martin Matthew Matzuk