Chimeric OspA genes, proteins and methods of use thereof
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-039/40
A61K-039/116
C12N-015/63
C12N-001/19
C12P-021/02
C07K-014/20
A61K-039/02
출원번호
US-0078367
(2013-11-12)
등록번호
US-9334311
(2016-05-10)
발명자
/ 주소
Crowe, Brian A.
Livey, Ian
O'Rourke, Maria
Schwendinger, Michael
출원인 / 주소
BAXALTA INCORPORATED
대리인 / 주소
Marshall, Gerstein & Borun LLP
인용정보
피인용 횟수 :
0인용 특허 :
20
초록▼
The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of
The invention relates to the development of chimeric OspA molecules for use in a new Lyme vaccine. More specifically, the chimeric OspA molecules comprise the proximal portion from one OspA serotype, together with the distal portion from another OspA serotype, while retaining antigenic properties of both of the parent polypeptides. The chimeric OspA molecules are delivered alone or in combination to provide protection against a variety of Borrelia genospecies. The invention also provides methods for administering the chimeric OspA molecules to a subject in the prevention and treatment of Lyme disease or borreliosis.
대표청구항▼
1. A nucleic acid molecule selected from the group consisting of: (a) a nucleic acid molecule comprising a nucleotide sequence with at least 98 percent sequence identity with the nucleotide sequence set forth in SEQ ID NO: 172;(b) a nucleic acid molecule comprising a nucleotide sequence comprising t
1. A nucleic acid molecule selected from the group consisting of: (a) a nucleic acid molecule comprising a nucleotide sequence with at least 98 percent sequence identity with the nucleotide sequence set forth in SEQ ID NO: 172;(b) a nucleic acid molecule comprising a nucleotide sequence comprising the nucleotide sequence set forth in SEQ ID NO: 172;(c) a nucleic acid molecule comprising a nucleotide sequence consisting of the nucleotide sequence set forth in SEQ ID NO: 172;(d) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide with at least 98 percent sequence identity with the amino acid sequence set forth in SEQ ID NO: 173; and(e) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 173, the polypeptide having a conservative substitution of one to 5 amino acids;(f) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 173, the polypeptide having an insertion of one to 5 amino acids;(g) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 173, the polypeptide having an internal deletion of one to 5 amino acids;(h) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 173, the polypeptide having a C- or N-terminal truncation of one to 5 amino acids, or a combined C- and N-terminal truncation of one to 5 amino acids;(i) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 173, the polypeptide having a modification of one to 5 amino acids selected from amino acid substitutions, amino acid insertions, amino acid deletions, a C-terminal truncation, or an N-terminal truncation; (i) wherein the substitutions, insertions, deletions, or modifications occur at any of amino acid positions 1-4, 6, 8, 9, 11, 16, 18, 20-28, 47, 49, 50, 81, 82, 83, 100 139, 155, 160, 176, 189, 190, and 250 of SEQ ID NO: 173; and(j) a nucleotide sequence complementary to any of (a) to (i). 2. The nucleic acid molecule of claim 1 further comprising a 5′-terminal outer surface protein B (OspB) nucleotide sequence fragment of Borrelia, wherein the OspB nucleotide sequence fragment comprises an OspB leader sequence. 3. A vector comprising the nucleic acid molecule of claim 1. 4. A host cell comprising the vector of claim 3. 5. A process of producing a polypeptide comprising culturing the host cell of claim 4 under conditions suitable to express the polypeptide, and optionally isolating the polypeptide from the culture. 6. A composition comprising the nucleic acid molecule of claim 1, and a pharmaceutically acceptable carrier. 7. The composition of claim 6 further comprising an additional nucleic acid molecule encoding an outer surface protein A (OspA) protein of Borrelia. 8. The composition of claim 7, wherein Borrelia is Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, Borrelia japonica, Borrelia andersonii, Borrelia bissettii, Borrelia sinica, Borrelia turdi, Borrelia tanukii, Borrelia valaisiana, Borrelia lusitaniae, Borrelia spielmanii, Borrelia miyamotoi or Borrelia lonestar. 9. The composition of claim 7, wherein the additional nucleic acid molecule is a chimeric nucleic acid molecule selected from the group consisting of: (a) a nucleic acid molecule comprising a first nucleotide sequence fragment from an outer surface protein A (OspA) serotype 6 protein coding region of Borrelia garinii and a second nucleotide sequence fragment from an OspA serotype 4 protein coding region of Borrelia garinii; (b) a nucleic acid molecule comprising a 5′-terminal nucleotide sequence encoding a fragment of the OspA serotype 6 protein coding region and a 3′-terminal nucleotide sequence encoding a fragment of the OspA serotype 4 protein coding region;(c) a nucleic acid molecule comprising a 5′-terminal nucleotide sequence encoding a fragment of the OspA serotype 4 protein and a 3′-terminal nucleotide sequence encoding a fragment of the OspA serotype 6 protein;(d) a nucleic acid molecule comprising a nucleotide sequence with at least or about 79 percent sequence identity with the nucleotide sequence set forth in SEQ ID NO: 170;(e) a nucleic acid molecule comprising a nucleotide sequence comprising the nucleotide sequence set forth in SEQ ID NO: 170;(f) a nucleic acid molecule comprising a nucleotide sequence consisting of the nucleotide sequence set forth in SEQ ID NO: 170;(g) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide with at least or about 79 percent sequence identity with a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 171;(h) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 171, the polypeptide having a substitution of one to 25 conservative amino acids;(i) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 171, the polypeptide having an insertion of one to 25 conservative amino acids:(j) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 171, the polypeptide having an internal deletion of one to 25 conservative amino acids;(k) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 171, the polypeptide having a C - and/or N-terminal truncation of one to 25 amino acids;(l) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 171, the polypeptide having a modification of one to 25 amino acids selected from amino acid substitutions, amino acid insertions, amino acid deletions, a C-terminal truncation, or an N-terminal truncation; (i) wherein the substitutions, insertions, deletions, or modifications occur at any of amino acid positions 1-4, 6, 8, 9, 11, 16, 18, 20-28, 47, 49, 50, 81, 82, 83, 100 139, 155, 160, 176, 189, 190, and 250 of SEQ ID NO: 171.(m) a nucleic acid molecule comprising a first nucleotide sequence fragment from an outer surface protein A (OspA) serotype 1 protein coding region of Borrelia burgdorferi sensu stricto and a second nucleotide sequence fragment from an OspA serotype 2 protein coding region of Borrelia afzelii; (n) a nucleic acid molecule comprising a 5′-terminal nucleotide sequence encoding a fragment of the OspA serotype 1 protein coding region and a 3′-terminal nucleotide sequence encoding a fragment of the OspA serotype 2 protein coding region;(o) a nucleic acid molecule comprising a 5′-terminal nucleotide sequence encoding a fragment of the OspA serotype 2 protein coding region and a 3′-terminal nucleotide sequence encoding a fragment of the OspA serotype 1 protein coding region;(p) a nucleic acid molecule comprising a nucleotide sequence with at least or about 79 percent sequence identity with the nucleotide sequence set forth in SEQ ID NO: 168;(q) a nucleic acid molecule comprising a nucleotide sequence comprising the nucleotide sequence set forth in SEQ ID NO: 168;(r) a nucleic acid molecule comprising a nucleotide sequence consisting of the nucleotide sequence set forth in SEQ ID NO: 168;(s) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 169, the polypeptide having a substitution of one to 25 conservative amino acids;(t) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 169, the polypeptide having an insertion of one to 25 conservative amino acids;(u) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 169, the polypeptide having an internal deletion of one to 25 conservative amino acids;(v) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 169, the polypeptide having a C - and/or N-terminal truncation of one to 25 amino acids;(w) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 169, the polypeptide having a modification of one to 25 amino acids selected from amino acid substitutions, amino acid insertions, amino acid deletions, a C-terminal truncation, or an N-terminal truncation; (i) wherein the substitutions, insertions, deletions, or modifications occur at any of amino acid positions 1-4, 6, 8, 9, 11, 16, 18, 20-28, 47, 49, 50, 81, 82, 83, 100 139, 155, 160, 176, 189, 190, and 250 of SEQ ID NO: 169;(x) a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide with at least or about 79 percent sequence identity with a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 169; and(y) a nucleotide sequence complementary to any one of (a) to (x). 10. A composition comprising at least two of the chimeric nucleic acid molecules in claim 9, wherein the nucleic acid molecules have different nucleotide sequences. 11. The composition of claim 10, wherein the nucleic acid molecules individually comprise the nucleotide sequences set forth in SEQ ID NOS: 168, 170, and 172. 12. An immunogenic composition comprising the composition of claim 10 and a pharmaceutically acceptable carrier. 13. The composition of claim 7, wherein the additional nucleic acid molecule further comprises a 5′-terminal outer surface protein B (OspB) fragment nucleotide sequence of Borrelia, wherein the OspB nucleotide sequence fragment comprises an OspB leader sequence. 14. The composition of claim 6 further comprising at least two additional nucleic acid molecules encoding an outer surface protein A (OspA) protein of Borrelia. 15. The nucleic acid molecule of claim 1 comprising a nucleotide sequence with at least 99 percent sequence identity with the nucleotide sequence set forth in SEQ ID NO: 172. 16. The nucleic acid molecule of claim 1 comprising the nucleotide sequence set forth in SEQ ID NO: 172. 17. The nucleic acid molecule of claim 1 consisting of the nucleotide sequence set forth in SEQ ID NO: 172. 18. The nucleic acid molecule of claim 1 comprising a nucleotide sequence encoding a polypeptide with at least 99 percent sequence identity with the amino acid sequence set forth in SEQ ID NO: 173. 19. The nucleic acid molecule of claim 1 comprising a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 173. 20. The nucleic acid molecule of claim 1 comprising a nucleotide sequence encoding a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 173.
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이 특허에 인용된 특허 (20)
Bergstrom Sven (Umea SEX) Barbour Alan G. (San Antonio TX), Borrelia antigen.
Queen Cary L. (Los Altos CA) Co Man Sung (Cupertino CA) Schneider William P. (Mountain View CA) Landolfi Nicholas F. (Milpitas CA) Coelingh Kathleen L. (San Francisco CA) Selick Harold E. (Belmont CA, Humanized immunoglobulins.
Berger Frank M. (190 E. 72nd St. New York NY 10021) Bona Constantin (New York NY) Lechevalier Mary P. (Piscataway NJ), Immunological adjuvant and process for preparing the same, pharmaceutical compositions, and process.
Aslam Muhammed (Rochester NY) Light William (Victor NY), Method of making a projection viewable transparency comprising an electrostatographic toner image.
Davis Frank F. (19 Farmingdale Rd. East Brunswick NJ 08816) Van Es Theodorus (313 Overbrook Rd. Piscataway NJ 08854) Palczuk Nicholas C. (45 W. Franklin St. Bound Brook NJ 08805), Non-immunogenic polypeptides.
Lockhoff Oswald (Cologne DEX) Hayauchi Yutaka (Leverkusen DEX) Stadler Peter (Haan DEX) Stnkel Klaus G. (Wuppertal DEX) Streissle Gert (Wuppertal DEX) Paessens Arnold (Haan DEX) Klimetzek Volker (Vel, Novel pharmaceutically active N-(2-aminoacylamido-2-deoxy-hexosyl)-amides, -carbamates and -ureas.
Cabilly Shmuel (Monrovia CA) Heyneker Herbert L. (Burlingame CA) Holmes William E. (Pacifica CA) Riggs Arthur D. (La Verne CA) Wetzel Ronald B. (San Francisco CA), Recombinant immunoglobin preparations.
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