Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Rodent cell – per se
Reexamination Certificate
1999-11-29
2002-04-23
Allen, Marianne P. (Department: 1631)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Rodent cell, per se
C536S023500, C435S069100, C435S320100, C435S325000, C435S354000
Reexamination Certificate
active
06376243
ABSTRACT:
BACKGROUND OF THE INVENTION
Throughout this application various publications are referred to by partial citations within parenthesis. Full citations for these publications may be found at the end of the specification immediately preceding the claims. The disclosures of these publications, in their entireties, are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
Primary amino acid sequence and signal transduction data are now published for four cloned 5-HT
1
-like receptors, three cloned 5-HT
2
receptors, and one 5-HT
3
receptor. Analysis of the sequence homology as well as the signal transduction pathways of these receptors leads to their grouping on the basis of these attributes: The 5-HT
1
subfamily includes: 5-HT
1A
(Kobilka et al., 1987; Fargin et al., 1988), 5-HT
1B
/5-HT
1D&bgr;
(Weinshank et al., 1992a; Adham et al., 1992; Jin et al., 1992), 5-HT
1D&agr;
(Branchek et al. 1991; Hamblin and Metcalf, 1991; Weinshank et al., 1992a), 5-HT
1E
(Levy et al., 1992; McAllister et al., 1992, Zgombick et al., 1992) and 5-HT
1F
(Amlaiky et al., 1992; Adham et al., in press). These subtypes share >50% transmembrane amino acid identity and couple to the inhibition of adenylate cyclase. The 5-HT
2
family includes the 5-HT
2
receptor (Pritchett et al., 1988), 5-HT
1C
(Julius et al., 1988) and 5-HT
2F
(Rat Stomach Fundus; Foquet et al., 1992; Kursar et al., 1992). These receptors share approximately 70% amino acid identity and coupling to phosphoinositide hydrolysis. The 5-HT
3
receptor has been shown to be a ligand-gated ion channel (Maricq et al., 1991). Heterogeneity of 5-HT
3
receptors is controversial, although other ligand-gated ion channels display significant heterogeneity. Notably absent from this series are the 5-HT
4
receptors. The second messenger coupling from tissue studies indicates activation of adenylate cyclase as a primary mode of signal transduction (Dumius et al., 1988; Bockaert et al., 1990). We report here the cloning of the first mammalian 5-HT receptor that couples to the stimulation of adenylate cyclase activity which we propose to name 5-HT
4B
. The pharmacological properties of this receptor indicate that it may be similar to a series of functionally defined 5-HT receptors described in the porcine vena cava (Trevethick et al., 1984), cat saphenous vein, coronary arteries (Cushing and Cohen, 1992), and several vascular dilatory effects (Mylecharane and Phillips, 1989). These receptors appear to underlie contractile and relaxant responses in isolated blood vessels indicating potential therapeutic benefit in angina, coronary artery disease, atherosclerosis, and possibly cerebral blood vessel disorders leading to stroke. The presence of this subtype in the CNS also indicates potential use in disorders of higher cognitive processes as well as control of autonomic function.
SUMMARY OF THE INVENTION
This invention provides an isolated nucleic acid molecule encoding a mammalian 5-HT
4B
receptor. In a preferred embodiment of this invention, the isolated nucleic acid encodes a human 5-HT
4B
receptor. In another embodiment of this invention, the nucleic acid molecule comprises a plasmid designated pcEXV-5-HT
4B
(ATCC Accession No. 75332).
This invention provides a nucleic acid probe comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a mammalian 5-HT
4B
receptor. This invention also provides a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a human 5-HT
4B
receptor.
This invention provides an antisense oligonucleotide having a sequence capable of binding specifically to an mRNA molecule encoding a mammalian 5-HT
4B
receptor so as to prevent translation of the mRNA molecule. This invention also provides an antisense oligonucleotide having a sequence capable of binding specifically to an mRNA molecule encoding a human 5-HT
4B
receptor so as to prevent translation of the mRNA molecule.
This invention provides a monoclonal antibody directed to a mammalian 5-HT
4B
receptor. This invention also provides a monoclonal antibody directed to a human 5-HT
4B
receptor.
This invention provides a pharmaceutical composition comprising an amount of a substance effective to alleviate the abnormalities resulting from overexpression of a mammalian 5-HT
4B
receptor and a pharmaceutically acceptable carrier as well as a pharmaceutical composition comprising an amount of a substance effective to alleviate abnormalities resulting from underexpression of mammalian 5-HT
4B
receptor and a pharmaceutically acceptable carrier.
This invention provides a pharmaceutical composition comprising an amount of a substance effective to alleviate the abnormalities resulting from overexpression of a human 5-HT
4B
receptor and a pharmaceutically acceptable carrier. This invention also provides pharmaceutical composition comprising an amount of a substance effective to alleviate abnormalities resulting from underexpression of a human 5-HT
4B
receptor and a pharmaceutically acceptable carrier.
This invention provides a transgenic, nonhuman mammal whose genome comprises DNA encoding a mammalian 5-HT
4B
receptor so positioned within such genome as to be transcribed into antisense mRNA complementary to mRNA encoding the mammalian 5-HT
4B
receptor and when hybridized to mRNA encoding the mammalian 5-HT
4B
receptor, the complementary mRNA reduces the translation of the mRNA encoding the mammalian 5-HT
4B
receptor.
This invention also provides a transgenic, nonhuman mammal whose genome comprises DNA encoding a human 5-HT
4B
so positioned within such genome as to be transcribed into antisense mRNA complementary to mRNA encoding the human 5-HT
4B
and when hybridized to mRNA encoding the human 5-HT
4B
, the complementary mRNA reduces the translation of the mRNA encoding the human 5-HT
4B
.
This invention provides a transgenic, nonhuman mammal whose genome comprises DNA encoding a mammalian 5-HT
4B
receptor positioned within such genome as to be transcribed into antisense mRNA which is complementary to mRNA encoding the mammalian 5-HT
4B
receptor and when hybridized to mRNA encoding the 5-HT
4B
receptor, the antisense mRNA thereby prevents the translation of mRNA encoding the 5-HT
4B
receptor.
This invention also provides a transgenic, nonhuman mammal whose genome comprises DNA encoding a human 5-HT
4B
receptor positioned within such genome as to be transcribed into antisense mRNA which is complementary to mRNA encoding the human 5-HT
4B
receptor and when hybridized to mRNA encoding human 5-HT
4B
receptor, the antisense mRNA thereby prevents the translation of mRNA encoding the 5-HT
4B
receptor.
This invention also provides a method of determining the physiological effects of expressing varying levels of a mammalian 5-HT
4B
receptor which comprises producing a transgenic nonhuman animal whose levels of mammalian 5HT
4B
receptor expression are varied by use of an inducible promoter which regulates mammalian 5-HT
4B
receptor expression.
This invention also provides a method of determining the physiological effects of expressing varying levels of a human 5-HT
4B
receptor which comprises producing a transgenic nonhuman animal whose levels of human 5-HT
4B
receptor expression are varied by use of an inducible promoter which regulates human 5-HT
4B
receptor expression.
This invention further provides a method of determining the physiological effects of expressing varying levels of mammalian 5-HT
4B
receptor which comprises producing a panel of transgenic nonhuman animals each expressing a different amount of mammalian 5-HT
4B
receptor.
This invention further provides a method of determining the physiological effects of expressing varying levels of human 5-HT
4B
receptor which comprises producing a panel of transgenic nonhuman animals each expr
Bard Jonathan A.
Branchek Theresa
Weinshank Richard L.
Allen Marianne P.
Cooper & Dunham LLP
Dunham Christopher C.
Synaptic Pharmaceutical Corporation
LandOfFree
DNA encoding a human serotonin receptor (5-HT4B) and uses... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with DNA encoding a human serotonin receptor (5-HT4B) and uses..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and DNA encoding a human serotonin receptor (5-HT4B) and uses... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2885863