Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1999-08-03
2002-02-12
Zitomer, Stephanie W. (Department: 1655)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C536S024330, C536S024300, C536S024310, C536S023500, C536S024500, C435S091100, C435S091200, C435S196000
Reexamination Certificate
active
06346380
ABSTRACT:
TECHNICAL FIELD
This invention relates to the detection of variations in human histamine H
2
receptors, and more particularly to the development of new compounds useful in the sequencing and identification of a human histamine H
2
receptor and their use in the diagnosis and treatment of certain human disorders, for example, brain disorders. The invention also relates to new compounds and a method for detecting an allelic polymorphic variation within the human population for the gene encoding the histamine H
2
receptor, and their use in the diagnosis and treatment of human disorders.
BACKGROUND OF THE INVENTION
The histamine H
2
receptor is one of many receptors in the body. Compounds used to treat many diseases work by activating a receptor or inhibiting the action of its natural ligand. Variations in some receptors amongst the population are known to be caused by allelic variation, and this variation can alter the response of a disease to a drug amongst patients. An example of this would be the response to clozapine, used to treat schizophrenia, associated with allelic variation in the 5-HT
2A
receptor demonstrated by Arranz el al (1995) Lancet, 346(8970), 281-282.
In co-pending UK Patent Applications Nos. GB9503866.7 and GB9522889.6, and in International Patent Application No. PCT/EP96/00397, it is reported that there is a hitherto unrecognised allele or subtype of the human histamine H
2
receptor gene which may be specific to the brain.
In the above mentioned co-pending patent specifications there are described and claimed:
1) a sequence for a novel allele of a human histamine H
2
receptor gene comprising up to six single base substitutions compared with the cDNA sequence published by Gantz et al (1991) Biochem Biophys Res Comm 178,3,1386-1392 as follows:
site of change
base change
amino acid alteration
398
T-C
Val-Gly
525
A-T
Lys-Asn
620
A-G
Lys-Asp
649
A-G
Asn-Asp
692
A-G
Lys-Arg
802
G-A
Val-Met
The cDNA sequence in Gantz et al., supra, is:
1
atggcaccca atggcacagc ctcttccttt tgcctggact ctaccgcatg caagatcacc
(SEQ ID NO:18)
61
atcaccgtgg tccttgcggt cctcatcctc atcaccgttg ctggcaatgt ggtcgtctgt
121
ctggccgtgg gcttgaaccg ccggctccgc aacctgacca attgtttcat cgtgtccttg
181
gctatcactg acctgctcct cggcctcctg gtgctgccct tctctgccat ctaccagctg
241
tcctgcaagt ggagctttgg caaggtcttc tgcaatatct acaccagcct ggatgtgatg
301
ctctgcacag cctccattct taacctcttc atgatcagcc tcgaccggta ctgcgctgtc
361
atggacccac tgcggtaccc tgtgctggtc accccagttc gggtcgccat ctctctggtc
421
ttaatttggg tcatctccat taccctgtcc tttctgtcta tccacctggg gtggaacagc
481
aggaacgaga ccagcaaggg caatcatacc acctctaagt gcaaagtcca ggtcaatgaa
541
gtgtacgggc tggtggatgg gctggtcacc ttctacctcc cgctactgat catgtgcatc
601
acctactacc gcatcttcaa ggtcgcccgg gatcaggcca agaggatcaa tcacattagc
661
tcctggaagg cagccaccat cagggagcac aaagccacag tgacactggc cgccgtcatg
721
ggggccttca tcatctgctg gtttccctac ttcaccgcgt ttgtgtaccg tgggctgaga
781
ggggatgatg ccatcaatga ggtgttagaa gccatcgttc tgtggctggg ctatgccaac
841
tcagccctga accccatcct gtatgctgcg ctgaacagag acttccgcac cgggtaccaa
901
cagctcttct gctgcaggct ggccaaccgc aactcccaca aaacttctct gaggtccaac
961
gcctctcagc tgtccaggac ccaaagccga gaacccaggc aacaggaaga gaaacccctg
1021
aagctccagg tgtggagtgg gacagaagtc acggcccccc agggagccac agacaggtaa
1081
aagctccagg tgtggagtgg gacagaagtc acggcccccc agggagccac agacaggtaa
1141
gcgctgaaca gagacttccg caccgggtac caacagctct tctgctgcag g
This cDNA sequence encodes the following amino acid sequence:
MAPNGTASSFCLDSTACKITITVVLAVLILITVAGNVVVCLAVGLNRRLRNLTNCFIVSLAITDLLLGLLVLPFSAI
(SEQ ID NO: 19)
YQLSCKWSFGKVFCNIYTSLDVMLCTASILNLFMISLDRYCAVMDPLRYPVLVTPVRVAISLVLIWVISITLSFLSI
HLGWNSRNETSKGNHTTSKCKVQVNEVYGLVDGLVTFYLPLLIMCITYYRIFKVARDQAKRINHISSWKAATIREHK
ATVTLAAVMGAFIICWFPYFTAFVYRGLRGDDAINEVKEAIVKWLGYANSALNPILYAAKNRDFRTGYQQLFCCRLA
NRNSHKTSLRSNASQLSRTQSREPRQQEEKPLKLQVWSGTEVTAPQGATDR
2) a nucleotide sequence coding for a region of a human histamine H
2
receptor, comprising one or more of the following base substitutions compared with the published sequence in Gantz et al (1991) supra, and from which the positional notation is taken:
site of change
base
398
C
525
T
620
G
649
G
692
G
802
A
The nucleotide sequence can, for example, comprise the following sequence (as listed in SEQ ID NO: 1):
5′ CAGCTCGGGTCGCCATCTCTCTGGTCTTAATTTGGGTCATCTCCATTACCCTGTC
CTTTCTGTCTATCCACCTGGGGTGGAACAGCAGGAACGAGACCAGCAAGGGCAAT
CATACCACCTCTAAGTGCAATGTCCAGGTCAATGAAGTGTACGGGCTGGTGGATG
GGCTGGTCACCTTCTACCTCCCGCTACTGATCATGTGCATCACCTACTACCGCAT
CTTCAGGGTCGCCCGGGATCAGGCCAAGAGGATCGATCACATTAGCTCCTGGAAG
GCAGCCACCATCAGGGAGCACAGAGCCACAGTGACACTGGCCGCCGTCATGGGGG
CCTTCATCATCTGCTGGTTTCCCTACTTCACCGCGTTTGTGTACCGTGGGCTGAG
AGGGGATGATGCCATCAATGAGATGTTA 3′
As a specific exemplification, the nucleotide sequence can comprise the following sequence (as listed in SEQ ID NO: 2):
5′ CCAATGGCACAGCCTCTTCCTTTTGCCTGGACTCTACCGCATGCAAGATCACCAT
CACCGTGGTCCTTGCGGTCCTCATCCTCATCACCGTTGCTGGCAATGTGGTCGTC
TGTCTGGCCGTGGGCTTGAACCGCCGGCTCCGCAACCTGACCAATTGTTTCATCG
TGTCCTTGGCTATCACTGACCTGCTCCTCGGCCTCCTGGTGCTGCCCTTCTCTGC
CATCTACCAGCTGTCCTGCAAGTGGAGCTTTGGCAAGGTCTTCTGCAATATCTAC
ACCAGCCTGGATGTGATGCTCTGCACAGCCTCCATTCTTAACCTCTTCATGATCA
GCCTCGACCGGTACTGCGCTGTCATGGACCCACTGCGGTACCCTGTGCTGGTCAC
CCCAGCTCGGGTCGCCATCTCTCTGGTCTTAATTTGGGTCATCTCCATTACCCTG
TCCTTTCTGTCTATCCACCTGGGGTGGAACAGCAGGAACGAGACCAGCAAGGGCA
ATCATACCACCTCTAAGTGCAATGTCCAGGTCAATGAAGTGTACGGGCTGGTGGA
TGGGCTGGTCACCTTCTACCTCCCGCTACTGATCATGTGCATCACCTACTACCGC
ATCTTCAGGGTCGCCCGGGATCAGGCCAAGAGGATCGATCACATTAGCTCCTGGA
AGGCAGCCACCATCAGGGAGCACAGAGCCACAGTGACACTGGCCGCCGTCATGGG
GGCCTTCATCATCTGCTGGTTTCCCTACTTCACCGCGTTTGTGTACCGTGGGCTG
AGAGGGGATGATGCCATCAATGAGATGTTAGAAGCCATCGTTCTGTGGCTGGGCT
ATGCCAACTCAGCCCTGAACCCCATCCTGTATGCTGCGCTGAACAGAGACTTCCG
CACCGGGTACCAACAGCTCTTCTGCTGCAGGCTGGCCAACCGCAACTCCCACAAA
ACTTCTCTGAGGTCCAACGCCTCTCAGCTGTCCAGGACCCAAAGCCGAGAACCCA
GGCAACAGGAAGAGAAACCCCTGAAGCTCCAGGTGTGGAGTGGGACAGAAGTCACG 3′
3) new oligonucleotides, suitable for use as primers for the amplification of DNA corresponding to a region of a human histamine H
2
receptor, having nucleotide sequences selected from:
1) 5′ CCAATGGCACAGCCTCTT 3′ (as listed in SEQ ID NO: 3)
2) 5′ CGTGACTTCTGTCCCACT 3′ (as listed in SEQ ID NO: 4)
3) 5′ CCAGGCAACAGGAAGAGA 3′ (as listed in SEQ ID NO: 5)
4) 5′ TCTCTTCCTGTTGCCTGG 3′ (as listed in SEQ ID NO: 6)
5) 5′ GCAGCAGAAGAGCTGTTG 3′ (as listed in SEQ ID NO: 7)
6) 5′ TCCAGGTCAATGAAGTGT 3′ (as listed in SEQ ID NO: 8)
7) 5′ ACACTTCATTGACCTGGA 3′ (as listed in SEQ ID NO: 9)
8) 5° CCAAGAGGATCAATCACA 3′ (as listed in SEQ ID NO: 10)
9) 5′ TGTGATTGATCCTCTTGG 3′ (as listed in SEQ ID NO: 11)
and
4) a diagnostic kit comprising one or more of the above new oligonucleotides.
DISCLOSURE OF THE INVENTION
The present invention is concerned in one aspect with improvements in the diagnosis and/or treatment of human neurological and psychiatric disorders, and more particularly in the diagnosis and treatment of schizophrenia. In another aspect, the invention is concerned with improvements in the diagnosis and/or treatment of diseases of other systems or organs of the human body.
According to the invention, a further group of oligonucleotides has now been developed for the id
Heath Paul
Orange Paul
Pearson Ronald Carl Alan
Wright Simon
Fish & Richardson P.C.
Unisheff Ventures Limited
Wilder Cynthia
Zitomer Stephanie W.
LandOfFree
Detection of variations in human H2 receptors does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Detection of variations in human H2 receptors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Detection of variations in human H2 receptors will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2976804