Howard L Fields

US Patent:

6838237, Jan 4, 2005

Filed:

Apr 18, 1997

Appl. No.:

09/171432

Inventors:

Howard A. Fields - Marietta GA, US
Yury E. Khudyakov - Duluth GA, US

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

C12Q 170
G01N 3353
C07K 1400
C07K 1410

US Classification:

435 5, 435 71, 530300, 530324, 530325

Abstract:

Antigenically reactive regions of the Hepatitis A virus polyprotein are provided. These antigenically reactive regions, and polypeptides and proteins comprising these antigenically reactive regions, provide a sensitive and specific immunological hepatitis A virus detection assay. The specific use of regions derived from the nonstructural regions of the polypeptide provides the basis for determining immunity derived from prior or present infection by the Hepatitis A virus and allows one to distinguish between an immunological response derived from infection and that derived from immunization.

US Patent:

6960659, Nov 1, 2005

Filed:

Jan 25, 2000

Appl. No.:

09/491146

Inventors:

Yury E. Khudyakov - Duluth GA, US
Howard A. Fields - Marietta GA, US

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

C07H021/04
C12N015/09
C12N015/51
A61K039/00
A61K039/29

US Classification:

536 2372, 435 691, 435 693, 435 697, 4241921, 4242281

Abstract:

A mosaic protein comprising a variety of immunoreactive antigenic epitopes from several genotypes of hepatitis C virus. The mosaic protein provides a sensitive and specific immunological hepatitis detection assay. A restriction enzyme assisted ligation method of making an artificial gene permits controlled construction of mosaic proteins, and allows confirmatory expression of the intermediate gene products.

US Patent:

7052696, May 30, 2006

Filed:

Jan 10, 2001

Appl. No.:

09/758308

Inventors:

Howard A. Fields - Marietta GA, US
Yury E. Khudyakov - Duluth GA, US

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

A61K 39/12
A61K 39/29
A61K 38/16
C07K 14/00
C07K 14/02
C07K 14/08

US Classification:

4241841, 4241851, 4241861, 4241891, 4241991, 42419611, 4242281, 424 91, 435 5, 435 71, 530350, 530300

Abstract:

Antigenic epitopes of hepatitis C virus (HCV) and mosaic HCV polypeptides useful as reagents in assays for the diagnosis or monitoring of HCV in a biological sample. The antigenic epitopes and mosaic polypeptides are also useful for the construction of immunogenic pharmaceutical compositions, such as vaccines. The mosaic polypeptides are artificial composite proteins constructed from diagnostically relevant antigenic regions derived from different HCV proteins. Preferably, the mosaic polypeptides contain antigenic epitopes from the core protein, NS3 protein, and NS4 protein. The preferred mosaic polypeptides optionally contain an additional antigenic epitope from either the NS4 protein or the NS5a protein or both.

US Patent:

7223535, May 29, 2007

Filed:

Dec 16, 2003

Appl. No.:

10/738443

Inventors:

Howard A. Fields - Marietta GA, US
Yury E. Khudyakov - Duluth GA, US

Assignee:

Centers for Disease Control - Atlanta GA

International Classification:

C12Q 1/70
C12P 15/00

US Classification:

435 5, 435 691

Abstract:

Synthetic peptides immunoreactive with hepatitis A virus (HAV) antibodies are provided. The peptides are useful as laboratory reagents to detect or quantify HAV antibodies in biological samples in clinical or research-based assays and for inducing an immune response to HAV when administered to a human or animal. The peptides contain antigenic epitopes, modified antigenic epitopes or combinations of epitopes of the major structural capsid polypeptides or non-structural polypeptides of HAV and contain one or more molecules of the amino acid glutamine (Q) at the carboxyl end of the peptide, which enhances immunoreactivity and immunogenicity, particularly IgM antibody reactivity.

US Patent:

20030220475, Nov 27, 2003

Filed:

May 19, 2003

Appl. No.:

10/257044

Inventors:

Howard Fields - Marietta GA, US
Yury Khudyakov - Duluth GA, US
Jiheng Mang - Atlantz GA, US

International Classification:

A61K048/00
A61K038/16
C07K014/02
C07K016/10

US Classification:

530/350000, 530/388300, 536/023720, 514/012000, 514/044000

Abstract:

The present invention provides immunogenic Hepatitis E Virus polypeptides and methods of use. The polypeptides include at least one neutralizing antigenic epitope and preferably contain at least about fifty amino acids residues between amino acid residues 452 and 617 from the C-terminal of the HEV pORF2 protein. The polypeptides are useful, alone or in combination with other polypeptides of the present invention, as a reagent for studying the pathogenesis of HEV and monitoring treatment efficacy in subjects undergoing treatment for HEV. Further, the polypeptides can be used as a vaccine to treat or prevent HEV.

US Patent:

55630324, Oct 8, 1996

Filed:

Feb 15, 1994

Appl. No.:

8/196945

Inventors:

Howard A. Fields - Marietta GA
Yury E. Khudyakov - Atlanta GA
Michael O. Favorov - Atlanta GA

Assignee:

The United States of America as represented by the Department of Health
and Human Services - Washington DC

International Classification:

C12Q 170
C07K 1408

US Classification:

435 5

Abstract:

A nucleic acid encoding a mosaic hepatitis E virus (HEV) polypeptide, consisting of the nucleotide sequence defined in the Sequence Listing as SEQ ID NO:1 is provided. A nucleic acid encoding epitopes 5, 6, 22, 23, 28 and 29 of hepatitis E virus and substantially lacking the nucleic acids intervening the epitope-coding nucleic acids in the native hepatitis E virus is also provided. An isolated nucleic acid that selectively hybridizes under stringent conditions with the mosaic polypeptide-encoding nucleic acid and has at least 70% sequence identity with SEQ ID NO:1 is provided. Also provided are such nucleic acids having at least 80%, 90% and 95% sequence identity. A polypeptide consisting essentially of the amino acid sequence defined in the Sequence Listing as SEQ ID NO:2 is provided. Polypeptides encoded by the present selectively hybridizing nucleic acids, and nucleic acids encoding epitopes 5, 6, 22, 23, 28 and 29 of HEV and substantially lacking the nucleic acids intervening the epitope-coding nucleic acids are also provided.

US Patent:

60226854, Feb 8, 2000

Filed:

Jun 7, 1995

Appl. No.:

8/484819

Inventors:

Howard A. Fields - Marietta GA
Michael O. Favorov - Atlanta GA
Yuri E. Khudyakov - Atlanta GA

Assignee:

United States of America - Washington DC

International Classification:

C12Q 170

US Classification:

435 5

Abstract:

The present invention provides antigenic peptides and polypeptides of hepatitis E virus. Also provided are mixtures of conjugated and unconjugated peptides of the present invention. Methods of detecting hepatitis E viral infection in a subject using the peptides and peptide mixtures of the present invention are also contemplated.

US Patent:

56703104, Sep 23, 1997

Filed:

Jul 29, 1994

Appl. No.:

8/282758

Inventors:

Howard A. Fields - Marietta GA
Yury E. Khudyakov - Atlanta GA

Assignee:

The United States of America as represented by the Department of Health
and Human Services - Washington DC

International Classification:

C12Q 170
G01N 33576
C07K 708

US Classification:

435 5

Abstract:

The present invention provides antigenic peptides which bind anti-HCV antibodies for the differential diagnosis of acute and chronic HCV infection. The invention further provides a method of differentiating acute and chronic hepatitis C virus infection in a subject comprising: a) contacting an antibody-containing sample from the subject with one or more of the peptides selected from the group consisting of peptide 59, comprising the amino acids AFASRGNHVSPTHYVPESDA (SEQ ID NO:1), peptide 137, comprising the amino acids MNRLIAFASRGNHVSPTHYV (SEQ ID NO:2) and peptide 138, comprising the amino acids SRGNHVSPTHYVPESDAAAR (SEQ ID NO:3) under conditions that permit binding between the peptide and the antibodies; b) detecting the presence of binding between the peptide and the antibodies; c) contacting the antibody-containing sample from the subject with an amount of peptide 139, comprising the amino acids NHVSPTHYVPESDAAARVTA (SEQ ID NO:4) under conditions that permit binding between the peptide and the antibodies; d) detecting the presence of binding between the peptide and the antibodies; and comparing the strength of the antibody binding of step b) with the strength of the antibody binding of step d), a stronger binding in step b) as compared to the binding in step d) indicating acute hepatitis C virus infection and an equivalent binding in both steps b) and d) indicating chronic hepatitis C virus infection. The present invention further provides a method of diagnosing a hepatitis C virus infection in a subject comprising contacting an antibody containing sample from the subject with a peptide comprising the amino acids SPTHYV (SEQ ID NO:5) and determining the presence of binding between the peptide and the antibodies from the sample, the presence of binding between the peptide and the antibodies indicating a hepatitis C virus infection.