CELL-PERMEABLE (CP)-DELTA SOCS3 RECOMBINANT PROTEIN AND USES THEREOF
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IPC분류정보
국가/구분
United States(US) Patent
공개
국제특허분류(IPC7판)
C07K-014/47
C07K-007/08
A61P-003/00
A61P-003/08
출원번호
US-0888459
(2018-02-05)
공개번호
US-0291073
(2018-10-11)
발명자
/ 주소
JO, Daewoong
출원인 / 주소
CELLIVERY THERAPEUTICS, INC.
인용정보
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초록▼
The present invention is related to development of the improved cell-permeable (CP)-ΔSOCS3 recombinant protein which disrupt the interaction of leptin receptor (ObR) and suppressor of cytokine signaling 3 (SOCS3), as protein-based anti-obesity or anti-diabetes agent by utilizing the platform technol
The present invention is related to development of the improved cell-permeable (CP)-ΔSOCS3 recombinant protein which disrupt the interaction of leptin receptor (ObR) and suppressor of cytokine signaling 3 (SOCS3), as protein-based anti-obesity or anti-diabetes agent by utilizing the platform technology for macromolecule intracellular transduction.
대표청구항▼
1.-30. (canceled) 31. A recombinant protein, which comprises a ΔSOCS3 protein containing a SH2 domain of SOCS3 protein; and an advanced macromolecule transduction domain (aMTD) being composed of 9˜13 amino acid sequences and having improved cell or tissue permeability, wherein the aMTD is fused to o
1.-30. (canceled) 31. A recombinant protein, which comprises a ΔSOCS3 protein containing a SH2 domain of SOCS3 protein; and an advanced macromolecule transduction domain (aMTD) being composed of 9˜13 amino acid sequences and having improved cell or tissue permeability, wherein the aMTD is fused to one end or both ends of the ΔSOCS3 protein and has the following features of:(a) being composed of 3 or more amino acids sequences selected from the group consisting of Ala, Val, Ile, Leu, and Pro;(b) having proline as amino acid sequences corresponding to any one or more of positions 5 to 8, and 12 of its amino acid sequence; and(c) having an instability index of 40-60; an aliphatic index of 180-220; and a grand average of hydropathy (GRAVY) of 2.1-2.6, as measured by Protparam. 32. The recombinant protein according to claim 31, wherein one or more solubilization domain (SD)(s) are further fused to the end(s) of one or more of the ΔSOCS3 protein and the aMTD. 33. The recombinant protein according to claim 31, wherein the aMTD is composed of 12 amino acid sequences and represented by the following general formula: Here, X(s) independently refer to Alanine (A), Valine (V), Leucine (L) or Isoleucine (I); and Proline (P) can be positioned in one of U(s) (either 5′, 6′, 7′ or 8′); and the remaining U(s) are independently composed of A, V, L or I, P at the 12′ is Proline. 34. A recombinant protein which is represented by any one of the following structural formulae: A-B—C, A-C—B, B-A-C, B—C-A, C-A-B, C—B-A and A-C—B—Cwherein A is an advanced macromolecule transduction domain (aMTD) having improved cell or tissue permeability, B is a ΔSOCS3 protein containing a SH2 domain of SOCS3 protein, and C is a solubilization domain (SD); andthe aMTD is composed of 9-13 amino acid sequences and has the following features of:(a) being composed of 3 or more amino acid sequences selected from the group consisting of Ala, Val, Ile, Leu, and Pro;(b) having proline as amino acid sequences corresponding to any one or more of positions 5 to 8, and 12 of its amino acid sequence;(c) having an instability index of 40-60; an aliphatic index of 180-220; and a grand average of hydropathy (GRAVY) of 2.1-2.6, as measured by Protparam; and(d) having α-Helix structure. 35. The recombinant protein according to claim 31, wherein the ΔSOCS3 protein has an amino acid sequence of SEQ ID NO: 816. 36. The recombinant protein according to claim 35, wherein the ΔSOCS3 protein is encoded by a polynucleotide sequence of SEQ ID NO: 817. 37. The recombinant protein according to claim 31, wherein the aMTD has an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-240 and 822. 38. The recombinant protein according to claim 37, wherein the aMTD is encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOs: 241˜480 and 823. 39. The recombinant protein according to claim 32, wherein the SD(s) have an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 798, 799, 800, 801, 802, 803, and 804. 40. The recombinant protein of claim 39, wherein the SD(s) are encoded by a polynucleotide sequence independently selected from the group consisting of SEQ ID NOs: 805, 806, 807, 808, 809, 810, and 811. 41. The recombinant protein according to claim 31, wherein the fusion is formed via a peptide bond or a chemical bond. 42. The recombinant protein according to claim 31, wherein the recombinant protein is used for the treatment or prevention of obesity or diabetes. 43. A polynucleotide sequence encoding the recombinant protein of claim 31. 44. The polynucleotide sequence according to claim 43, wherein the polynucleotide sequence is represented by SEQ ID NO: 819. 45. A polynucleotide sequence encoding the recombinant protein of claim 34. 46. The polynucleotide sequence according to claim 45, wherein the polynucleotide sequence is represented by SEQ ID NOs: 821. 47. A recombinant expression vector comprising the polynucleotide sequence of claim 43. 48. A transformant transformed with the recombinant expression vector of claim 47. 49. A preparing method of the recombinant protein comprising: culturing the transformant of claim 48 in a culture medium to produce the recombinant protein;and recovering the recombinant protein expressed by the culturing. 50. A pharmaceutical composition for treating or preventing obesity or diabetes comprising the recombinant protein of claim 31 as an active ingredient; and a pharmaceutically acceptable carrier. 51. A method of treating or preventing obesity or diabetes in a subject comprising: administering to the subject a therapeutically effective amount of the recombinant protein of claim 31.
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