Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Reexamination Certificate
1998-03-24
2001-10-16
Wortman, Donna C. (Department: 1648)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
C436S820000, C530S350000
Reexamination Certificate
active
06303292
ABSTRACT:
TECHNICAL FIELD
This invention relates generally to immunoreactive polypeptide compositions, methods of using the compositions in immunological applications, and materials and methods for making the compositions.
BACKGROUND
The hepatitis C virus has been recently identified as the major causative agent of post-transfusion Non-A, Non-B hepatitis (NANHB), as well as a significant cause of community-acquired NANBH. Materials and methods for obtaining the viral genomic sequences are known. See, e.g. PCT Publication Nos. WO89/04669, WO90/11089 & WO90/14436.
Molecular characterization of the HCV genome indicates that it is a RNA molecule of positive polarity containing approximately 10,000 nucleotides that encodes a polyprotein of about 3011 amino acids. Several lines of evidence suggest that HCV has a similar genetic organization to the viruses of the family Flaviviridae, which includes the flavi- and pestivirus. Like its pesti- and flaviviral relatives, HCV appears to encode a large polyprotein precursor from which individual viral proteins (both structural and non-structural) are processed.
RNA-containing viruses can have relatively high rates of spontaneous mutation, i.e., reportedly on the order of 10
−3
to 10
−4
per incorporated nucleotide. Therefore, since heterogeneity and fluidity of genotype are common in RNA viruses, there may be multiple viral isolates, which may be virulent or avirulent, within the HCV species.
A number of different isolates of HCV have now been identified. The sequences of these isolates demonstrate the limited heterogeneity characteristic of RNA viruses.
Isolate HCV J1.1 is described in Kubo, Y. et al. (1989), Japan. Nucl. Acids Res. 17:10367-10372; Takeuchi, K. et al.(1990), Gene 91:287-291; Takeuchi et al. (1990), J. Gen. Virol. 71:3027-3033; Takeuchi et al. (1990), Nucl. Acids Res. 18:4626.
The complete coding sequences plus the 5′- and 3′-terminal sequences of two independent isolates, “HCV-J” and “BK”, are described by Kato et al. and Takamizawa et al, respectively. (Kato et al. (1990), Proc. Natl. Acad. Sci. USA 87:9524-9528; Takamizawa et al (1991), J. Virol. 65:1105-1113.)
Other publications describing HCV isolates are the following;
“HCV-1”: Choo et al (1990), Brit. Med. Bull. 46:423-441; Choo et al. (1991), Proc.
Natl. Acad. Sci. USA 88:2451-2455; Han et al. (1991), Proc. Natl. Acad. Sci. USA 88:1711-1715; European Patent Publication No. 318,216.
“HC-J1” and “HC-J4”: Okamoto et al. (1991), Japan J. Exp. Med. 60:167-177.
“HCT 18”, “HCT 23”, “Th”, “HCT 27”, “EC1” and “EC10”: Weiner et al. (1991), Virol. 180:842-848.
“Pt-1”, “HCV-K1” and “HCV-K2”: Enomoto et al, There are two major types of hepatitis C virus in Japan. Division of Gastroenterology, Department of Internal Medicine, Kanazawa Medical University, Japan.
Clones “A”, “C”, “D” & “E”: Tsukiyama-Kohara et al., A second group of hepatitis virus, in Virus Genes.
A typical approach to diagnostic and vaccine strategy is to focus on conserved viral domains. This approach, however, suffers from the disadvantage of ignoring important epitopes that may lie in variable domains.
It is an object of this invention to provide polypeptide compositions that are immunologically cross-reactive with multiple HCV isolates, particularly with respect to heterogeneous domains of the virus.
SUMMARY OF THE INVENTION
It has been discovered that a number of important HCV epitopes vary among viral isolates, and that these epitopes can be mapped to particular domains. This discovery allows for a strategy of producing immunologically cross-reactive polypeptide compositions that focuses on variable (rather than conserved) domains.
Accordingly, one embodiment of the present invention is an immunoreactive composition comprising polypeptides wherein the polypeptides comprise the amino acid sequence of an epitope within a first variable domain of HCV, and at least two heterogeneous amino acid sequences from the first variable domain of distinct HCV isolates are present in the composition.
Another embodiment of the invention is an immunoreactive composition comprising a plurality of antigen sets, wherein (a) each antigen set consists of a plurality of substantially identical polypeptides comprising the amino acid sequence of an epitope within a first variable domain of an HCV isolate, and (b) the amino acid sequence of the epitope of one set is heterogeneous with respect to the amino acid sequence of the analogous sequence of at least one other set.
Another embodiment of the invention is an immunoreactive composition comprising a plurality of polypeptides wherein each polypeptide has the formula
R
r
−(SV
n
)
x
−R′
r′
wherein
R and R′ are amino acid sequences of about 1-2000 amino acids, and are the same or different;
r and r′ are 0 or 1, and are the same or different;
V is an amino acid sequence comprising the sequence of an HCV variable domain, wherein the variable domain comprises at least one epitope;
S in an integer ≧1, representing a selected variable domain; and
n is an integer ≧1, representing a selected HCV isolate heterogeneous at a given SV with respect to at least one other isolate having a different value for n, and n being independently selected for each x;
x is an integer ≧1; and with the proviso that amino acid sequences are present in the composition representing a combination selected from the group consisting of (i) 1V
1
and 1V
2
, (ii) 1V
1
and 2V
2
, and (iii) 1V
1
and 2V
1
.
Yet another embodiment of the invention is a method for preparing an immunogenic pharmaceutical composition HCV comprising:
(a) providing an immunoreactive composition as described above;
(b) providing a suitable excipient; and
(c) mixing the immunoreactive composition of (a) with the excipient of (b) in a proportion that provides an immunogenic response upon administration to a mammal.
Still another embodiment of the invention is a method for producing anti-HCV antibodies comprising administering to a mammal an effective amount of an immunoreactive composition as described above.
Yet another embodiment of the invention is a method of detecting antibodies to HCV within a biological sample comprising:
(a) providing a biological sample suspected of containing antibodies to HCV;
(b) providing an immunoreactive composition described above;
(c) reacting the biological sample of (a) with the immunoreactive composition of (b) under conditions which allow the formation of antigen-antibody complexes; and
(d) detecting the formation of antigen-antibody complexes formed between the immunoreactive composition of (a) and the antibodies of the biological sample of (b), if any.
Another embodiment of the invention is a kit for detecting antibodies to HCV within a biological sample comprising an immunoreactive composition as described above packaged in a suitable container.
REFERENCES:
patent: 5350671 (1994-09-01), Houghton et al.
patent: 5372928 (1994-12-01), Miyamura et al.
patent: 5670152 (1997-09-01), Weiner et al.
patent: 318216 (1989-05-01), None
patent: 0318216 (1989-05-01), None
patent: 0388232 (1990-09-01), None
patent: 0149182 A1 (1991-03-01), None
patent: 89/04669 (1989-06-01), None
patent: 90/11089 (1990-10-01), None
patent: 90/14436 (1990-11-01), None
Takamizawa et al., “Stucture and organization . . . ”,J. of Virology, (1991) 65(3):1105-1113.
Goodenow et al., “HIV-1 isolates are rapidly evolving . . . ”J. of Acquiried Immune Deficiency Syndromes, (1989) 2(4):344-352.
Weiner et al., “Variable and hypevariable domains . . . ”Virlogy(1991) 180:842-848.
Weiner et al., “Evidence for immune selection of hepatitis C . . . ”Proc. Natl. Acad. Sci. USA(1992) 89:3468-3472.
Okamoto et al., “Nucleotide Sequence of the genomic RNA . . . ”J. of General Virology(1991) 72(11):2697-2704.
Kremsdorf et al., “Partial nucleotide sequence analysis . . . ”J. of General Virology(1991) 72:2557-2561.
Neurath et al., “Confronting the hypervariability . . . ”Molecular Immun.(1990) 27(6):539-549.
Haigwood et al., “Importance of hypervariable regions . . . ”Aids Research and Human Retrovi
Houghton Michael
Weiner Amy J.
Blackburn Robert P.
Chiron Corporation
Harbin Alisa A.
Wortman Donna C.
LandOfFree
Immunoreactive polypeptide compositions does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Immunoreactive polypeptide compositions, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Immunoreactive polypeptide compositions will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2555420