Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues
Reexamination Certificate
2001-08-08
2003-09-23
Fredman, Jeffrey (Department: 1637)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
C514S002600, C514S003100
Reexamination Certificate
active
06624287
ABSTRACT:
TECHNICAL FIELD
The invention relates to a method for searching various types of novel physiologically active substances and a process for producing same, and drugs found by the searching method.
RELATED ART
In the prior art, the searching for unknown physiologically active substances involved analyzing constituents present in body fluids or tissues, identifying and isolating novel substances and investigating the physiological activity of the discovered novel substances.
The method of the prior art described above consists of analyzing constituents present in the body, finding novel substances and investigating their physiological activities. However, the number of constituents present in the body is extremely high, and physiologically active substances are often present only in low concentrations, thereby making finding novel substances a difficult task. Further, because an overwhelming number of physiological reactions take place in the body, and thus, finding the nature of physiological activities the newly found substances have is also difficult. Therefore, finding novel physiologically active substances with the method of the prior art is a difficult task.
DISCLOSURE OF THE INVENTION
Therefore, one of the objects of the invention is to provide a more efficient method for searching novel physiologically active substances with a certain level of predictability. Furthermore, another one of the objects of the invention is to provide a process for producing the physiologically active substances found by the method described above. In addition, one of the objects of the invention is to provide a novel medicine for treating diabetes, insulin production regulators, gastric acid secretion regulators and growth hormone secretion regulators found by the method of the invention described above.
The inventors have previously invented a more efficient method for searching novel physiologically active substances with a certain level of predictability and filed a patent application (Patent Laid-open Publication No Hei. 10-109997). The method is based on the finding that, among receptors of substances, for which substances or cells having antagonizing effects are present in a body, or, receptors for the Substance A, for which cells or substances having antagonizing effects on cells responding to said Substance A are present in a body, when there exist two or more sizes for the same receptor, the missing portions, i.e. the portions of amino acid sequences which have been spliced, have physiological activities related to said receptor.
The inventors completed the invention after actually verifying that, in performing the searching method of the previously applied patent described above, the method of inferring the amino acid sequences of receptors based on the base sequences of their cDNAs is also valid when two or more cDNA sequences exist for said receptors, and that its is not restricted to the ones based on the amino acid sequences of receptors whose actual existences are known.
Namely, the invention provides a method for searching physiologically active substances comprising, examining a peptide having an amino acid sequence of two or more sizes for the same receptor by comparing the cDNA sequences of said receptor, wherein the receptor is a receptor of a cell producing an antagonist to a substance present in a body or a receptor of a cell producing an antagonist to said cells per se, and then examining which regions of the longer receptor are missing in the shorter receptor by comparing the sequences of the above-mentioned cDNAs. Also, the invention provides a method for producing physiologically active peptides wherein the missing regions, established by the method of the invention described above, or their derivatives are produced. In addition, the invention provides a medicine for treating diabetes comprising, as an active component, a peptide having the effect of increasing the production of insulin by insulin producing cells, said peptide being those successfully searched for and found by the method of the invention described above and having the amino acid sequences indicated by SEQ. ID. NO: 1 or SEQ. ID. NO: 5, or having amino acid sequences obtained by the substitution inside, deletion from, insertion into or addition to said SEQ. ID. NO: 1 or SEQ. ID. NO: 5 of one or several amino acids. In addition, the invention provides insulin production regulators comprising, as an active component, a peptide having the effect of regulating the production of insulin by insulin producing cells, said peptides having the amino acid sequence indicated by SEQ. ID. NO: 2, or having amino acid sequences obtained by the substitution inside, deletion from, insertion into or addition to SEQ. ID. NO: 2 of one or several amino acids. In addition, the invention provides gastric acid secretion regulators comprising, as an active component, a peptide having the effect of regulating the secretion of gastric acid, said peptides having the amino acid sequences indicated by SEQ. ID. NO: 3 or SEQ. ID. NO: 4, or having amino acid sequences obtained by the substitution inside, deletion from, insertion into or addition to SEQ. ID. NO: 3 or SEQ. ID. NO: 4 of one or several amino acids. Growth hormone production regulators are provided, comprising, as an active component, peptides having the effects of regulating the production of hormone, and having the amino acid sequence indicated by SEQ. ID. NO: 6 or having amino acid sequences obtained by the substitution inside, deletion from, insertion into or addition to SEQ. ID. NO: 6 of one or several amino acids.
The invention provides a method based on the base sequences of cDNAs, for efficiently searching novel physiologically active substances with a certain level of predictability. In the method of the invention, novel biologically active substances can be found by examining the receptors for substances participating in antagonism, therefore, it is not required as in the prior art, to isolate physiologically active substances present in trace amounts inside biological samples containing extremely large number of constituents. In addition, the physiological activity of the searched and found physiologically active substance is an activity participating in the antagonism described above, therefore, searching for its physiological activity is also considerably easier than that of the prior art. Thus, according to the method of the invention, searching for novel physiologically active substances can be performed with a considerably higher efficiency compared to the related art. Also, the invention provides a novel medicine for treating diabetes having excellent increased effects on insulin production. In addition, novel insulin production regulators, gastric acid secretion regulators and growth hormone production stimulators are provided.
PREFERRED EMBODIMENTS OF THE INVENTION
In the method for searching physiologically active substances of the invention, among receptors of cells producing an antagonist to a substance in a body, or among receptors of cells producing an antagonist to said cells per se, amino acid sequences of two or more sizes for a same receptor are examined by comparing the cDNA sequences of the receptor and then which region of the longer receptor is missing in the shorter receptor is examined by comparing the sequences of the above-mentioned cDNAs or the sequences of mature mRNAs.
Namely, the method of the invention concerns cases where two or more receptors with different sizes are generated based on the differences in the base sequences of the mature mRNAs. In other words, the method of the invention searches for splicing variations at the level of the mRNAs. The role of splicing resulting from the splicing variation at the level of mRNAs, which normally does not occur, is not well understood, except that it inactivates gene expression. There are cases where sequences which should originally be translated are consequently not translated, and in contrast, there are cases where sequences which should not be translated are expressed. In most insta
Brooks & Kushman P.C.
Chunduru Psrabha
Fredman Jeffrey
Sakamoto Kenji
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