Novel secretory proteins and dna thereof

• US 20040248790A1
• Filed: 06/15/2004
• Published: 12/09/2004
• Est. Priority Date: 09/03/2001
• Status: Abandoned Application

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Noguchi, Yuko, Kitada, Chieko, Harada, Masataka, Komatsu, Hidetoshi, Habata, Yugo, Fujii, Ryo, Hinuma, Shuji, Fukusumi, Shoji, Hosoya, Masaki
• Application Number:
  US10/488,480
• Publication Number:
  US 20040248790A1
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/47 from mammals

Abstract

Secretory proteins comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by, for example, SEQ ID NO: 23 are useful physiologically active substances binding to AQ27 receptor.

Claims

1-383. -383. (cancelled).

384. A secretory protein comprising the same or substantially the same amino acid sequence as an amino acid sequence in positions 19 to 136 of the amino acid sequence represented by SEQ ID NO:

23, its amide or ester, or a salt thereof.

388. A partial peptide of the secretory protein according to claim 384 or the peptide according to claim 386, its amide or ester, or a salt thereof.

389. A precursor protein of the secretory protein according to claim 384 or the peptide according to claim 386, its amide or ester, or a salt thereof.

390. The precursor protein according to claim 389, which comprises the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

23, or a salt thereof.

392. A polynucleotide comprising a polynucleotide encoding the secretory protein according to claim 384.

393. The polynucleotide according to claim 392, which consists of a nucleotide sequence in positions 55 to 408 of the nucleotide sequence represented by SEQ ID NO:

24.

396. A polynucleotide comprising a polynucleotide encoding the partial peptide according to claim 388.

397. A polynucleotide comprising a polynucleotide encoding the precursor protein according to claim 389.

398. The polynucleotide according to claim 397, which consists of the nucleotide sequence represented by SEQ ID NO:

24.

399. A recombinant vector comprising the polynucleotide according to claim 392.

400. A transformant transformed with the recombinant vector according to claim 399.

401. A process for producing the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, which comprises culturing the transformant according to claim 400 to form the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein.

402. An antibody to the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof.

403. The antibody according to claim 402, which is a neutralizing antibody inactivating the activity of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof.

404. A pharmaceutical comprising the antibody according to claim 402.

405. A diagnostic agent comprising the antibody according to claim 402.

406. A pharmaceutical comprising the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof.

407. A pharmaceutical comprising the polynucleotide according to claim 392.

408. A diagnostic agent comprising the polynucleotide according to claim 392.

409. An antisense polynucleotide comprising the whole or a part of a nucleotide sequence complementary to the polynucleotide according to claim 392.

410. A pharmaceutical comprising the antisense polynucleotide according to claim 409.

411. A diagnostic agent comprising the antisense polynucleotide according to claim 409.

412. A method of screening a compound or its salt that promotes or suppresses the functions of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, which comprises using the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof.

413. A kit for screening a compound or its salt that promotes or suppresses the functions of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, which comprises the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof.

414. A compound or its salt that promotes or suppresses the functions of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, which is obtainable using the screening method according to claim 412 or the screening kit according to claim 413.

415. A pharmaceutical comprising a compound or its salt that promotes or suppresses the functions of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof.

416. A method of screening a compound or its salt that promotes or suppresses the expression of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, which comprises using the polynucleotide according to claim 392.

417. A kit for screening a compound or its salt that promotes or suppresses the expression of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, which comprises the polynucleotide according to claim 392.

418. A compound or its salt that promotes or suppresses the expression of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, which is obtainable using the screening method according to claim 416 or the screening kit according to claim 417.

419. A pharmaceutical comprising a compound or its salt that promotes or suppresses the expression of the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof.

420. A method of screening a compound or its salt that alters the binding property between (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof and (ii) G protein-conjugated receptor protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

31, SEQ ID NO;

44 or SEQ ID NO;

46, its partial peptide or a salt thereof, which comprises using (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof and (ii) G protein-conjugated receptor protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO;

31, SEQ ID NO;

44 or SEQ ID NO;

46, its partial peptide or a salt thereof.

421. A compound or its salt that alters the binding property between (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof and (ii) G protein-conjugated receptor protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

31, SEQ ID NO;

44 or SEQ ID NO;

46, its partial peptide or a salt thereof, which is obtainable using the screening method according to claim 420.

422. A pharmaceutical comprising a compound or its salt that alters the binding property between (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof and (ii) G protein-conjugated receptor protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

31, SEQ ID NO;

44 or SEQ ID NO;

46, its partial peptide or a salt thereof, which is obtainable using the screening method according to claim 420.

423. A method of screening a compound or its salt that alters the binding property between (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof and (ii) G protein-conjugated receptor protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

33 or SEQ ID NO;

35, its partial peptide or a salt thereof, which comprises using (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof and (ii) G protein-conjugated receptor protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO;

33 or SEQ ID NO;

35, its partial peptide or a salt thereof.

424. A compound or its salt that alters the binding property between (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof and (ii) G protein-conjugated receptor protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

33 or SEQ ID NO;

35, its partial peptide or a salt thereof, which is obtainable using the screening method according to claim 423.

425. A pharmaceutical comprising a compound or its salt that alters the binding property between (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof and (ii) G protein-conjugated receptor protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

33 or SEQ ID NO;

35, its partial peptide or a salt thereof, which is obtainable using the screening method according to claim 423.

426. The pharmaceutical according to any one of claims 404, 406, 407, 410, 415, 419, 422, or 425, which is a hormone secretion regulator, an eating regulator, a sleep regulator, an arousal regulator, a pain regulator, a stress response regulator, a spontaneous behavior regulator or an emotional behavior regulator.

427. A pharmaceutical according to any one of claims 404, 406, 407, 410, 415, 419, or 422, which is a prolactin secretion regulator.

428. A method of regulating hormone secretion, eating, sleep, arousal, pain, stress response, spontaneous behavior or emotional behavior, which comprises administering, to a mammal, an effective amount of (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, (ii) the polynucleotide according to claim 392, (iii) the antibody according to claim 402, (iv) the antisense polynucleotide according to claim 409, (v) the compound or its salt according to claim 414, (vi) the compound or its salt according to claim 418, or (vii) the compound or its salt according to claim 421.

429. A method of regulating prolactin secretion, which comprises administering, to a mammal, an effective amount of (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, (ii) the polynucleotide according to claim 392, (iii) the antibody according to claim 402, (iv) the antisense polynucleotide according to claim 409, (v) the compound or its salt according to claim 414, (vi) the compound or its salt according to claim 418 or (vii) the compound or its salt according to claim 424.

430. Use of (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, (ii) the polynucleotide according to claim 392, (iii) the antibody according to claim 402, (iv) the antisense polynucleotide according to claim 409, (v) the compound or its salt according to claim 414, (vi) the compound or its salt according to claim 418 or (vii) the compound or its salt according to claim 421.

431. Use, in production of a prolactin secretion regulator, of (i) the secretory protein according to claim 384 or the peptide according to claim 386, its partial peptide or precursor protein, its amide or ester, or a salt thereof, (ii) the polynucleotide according to claim 392, (iii) the antibody according to claim 402, (iv) the antisense polynucleotide according to claim 409, (v) the compound or its salt according to claim 414, (vi) the compound or its salt according to claim 418 or (viii) the compound or its salt according to claim 424.

432. The secretory protein according to claim 384, wherein the same or substantially the same amino acid sequence as an amino acid sequence in positions 19 to 136 of the amino acid sequence represented by SEQ ID NO:

23 is an amino acid sequence in positions 18 to 124 of the amino acid sequence represented by SEQ ID NO;

27, an amino acid sequence in positions 18 to 124 of the amino acid sequence represented by SEQ ID NO;

38 or an amino acid sequence in positions 18 to 134 of the amino acid sequence represented by SEQ ID NO;

42, its amide or ester, or a salt thereof.

433. The precursor protein according to claim 389, wherein the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:

23 is the amino acid sequence represented by SEQ ID NO;

27, the amino acid sequence represented by SEQ ID NO;

38 or the amino acid sequence represented by SEQ ID NO;

42, or a salt thereof.

385. A secretory protein consisting of an amino acid sequence in positions 19 to 136 of the amino acid sequence represented by SEQ ID NO:

23, its amide or ester, or a salt thereof.

386. A peptide comprising the same or substantially the same amino acid sequence as an amino acid sequence in positions 26 to 88, an amino acid sequence in positions 80 to 88, an amino acid sequence in positions 91 to 133 or an amino acid sequence in positions 127 to 133 of the amino acid sequence represented by SEQ ID NO:

23, its amide or ester, or a salt thereof.

394. A polynucleotide comprising a polynucleotide encoding the peptide according to claim 386.

395. The polynucleotide according to claim 394, which consists of a nucleotide sequence in positions 76 to 264, a nucleotide sequence in positions 238 to 264, positions 271 to 399 or positions 379 to 399 of the nucleotide sequence represented by SEQ ID NO:

24.

387. A peptide consisting of an amino acid sequence in positions 26 to 88, an amino acid sequence in positions 80 to 88, an amino acid sequence in positions 90 to 133, an amino acid sequence in positions 91 to 133, an amino acid sequence in positions 93 to 133, an amino acid sequence in positions 104 to 133, an amino acid sequence in positions 108 to 133, an amino acid sequence in positions 109 to 133, an amino acid sequence in positions 111 to 133, an amino acid sequence in positions 115 to 133, an amino acid sequence in positions 119 to 133, an amino acid sequence in positions 124 to 133, an amino acid sequence in positions 126 to 133 or an amino acid sequence in positions 127 to 133 of the amino acid sequence represented by SEQ ID NO:

23, its amide or ester, or a salt thereof.

391. A precursor protein consisting of the amino acid sequence represented by SEQ ID NO:

23, its amide or ester, or a salt thereof.