04-20656. Licensing Opportunity and/or Cooperative Research and Development Agreement (“CRADA”) Opportunity: Live Attenuated Respiratory Syncytial Virus (RSV), Human Metapneumovirus (HMPV), and Parainfluenza Virus (PIV) Vaccines

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

SUMMARY:

The National Institutes of Health (NIH) is seeking Licensee(s) and/or a commercial collaborator(s) to further develop, test, and commercialize as live attenuated virus vaccines certain recombinant RSV, HMPV and/or PIV strains and associated intellectual property developed in the Laboratory of Infectious Diseases (LID), Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID).

DATES:

Respondents interested in licensing the invention will be required to submit an “Application for License to Public Health Service Inventions” to NIH (attention Susan Ano, Ph.D. at the address mentioned below) on or before November 15, 2004, for priority consideration.

Potential CRADA collaborators must submit a letter summarizing their interests and capabilities to the NIAID (attention Richard K. Williams, Ph.D. at the address mentioned below) on or before November 15, 2004, for consideration. Guidelines for preparing full CRADA proposals will be communicated shortly thereafter to all respondents with whom initial confidential discussions will have established sufficient mutual interest.

CRADA and PHS License Applications submitted thereafter may be considered if a suitable CRADA collaborator or Licensee(s) has not been selected.

FOR FURTHER INFORMATION CONTACT:

Inquiries about these licensing opportunities should be addressed to Susan Ano, Ph.D., Technology Licensing Specialist, Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: [phone]; facsimile: [phone]; e-mail: [e-mail]. Information about Patent Applications and pertinent information not yet publicly described can be obtained under the terms of a Confidential Disclosure Agreement. Respondents interested in licensing the inventions will be required to submit an “Application for License to Public Health Service Inventions”.

Depending upon the mutual interests of the Licensee(s) and the NIAID, a CRADA to collaborate to develop RSV, HMPV, and/or PIV vaccines in humans may also be negotiated. Proposals and questions about this CRADA opportunity should be addressed to Richard K. Williams, Ph.D., Technology Development Associate, Office of Technology Development, NIAID, 6610 Rockledge Drive, Room 4071, Bethesda, MD 20892-6606; telephone: [phone]; e-mail: [e-mail]. Respondents interested in submitting a CRADA Proposal should be aware that it may be necessary to secure a license to the above-mentioned patent rights in order to commercialize products arising from a CRADA.

SUPPLEMENTARY INFORMATION:

The portfolios listed below describe approaches to the development of live, attenuated vaccines for intranasal delivery against respiratory syncytial virus (RSV) subgroups A and B, human metapneumovirus (HMPV), and three parainfluenza viruses (PIV1, -2, and -3), which account for up to 55-60% of serious respiratory tract infection in children and infants less than one year of age. Live attenuated viruses are the most promising candidate vaccines because they induce both local and systemic immunity and are efficacious even in the presence of passively transferred serum antibodies, the very situation found in the target population of infants with maternally derived antibodies.

These patents and patent applications describe broadly the generation of live attenuated vaccine viruses from recombinant cDNA clones for RSV, HMPV and PIV1, 2 and 3. For RSV and the PIVs, attenuation is achieved by missense mutations optimized for genetic stability, by gene deletion (e.g. E-089-1997; E-194-1999), by deletion of codons, by host range sequences (e.g. E-178-1999; E-201-2000; E-202-1999; E-187-1995), or by a combination of these (e.g. E-142-1996). HMPV has been attenuated by gene deletion (E-093-2003) and should be amenable to the other methods as well. Chimeras are described that contain the protective antigens of RSV subgroup B on an attenuated subgroup A background (e.g. E-178-1999), using a single attenuated backbone to make vaccines against both subgroups. Importantly, each of PIV viruses can be used as stable, efficient vectors for expressing the protective antigens of RSV, HMPV, or other viral pathogens in a schedule that permits boosting of immune responses (e.g. E-099-1999; E-089-1997; E-280-2001; E-092-2002). In this strategy, the PIV vector is a needed vaccine in addition to the expressed RSV/HMPV antigens, resulting in a bi- or multi-valent vaccine virus.

Augmentation of the immune response to the protective antigens can be achieved by positioning them in a more promoter proximal position (e.g. E-225-2000), by altering the regulation of viral transcription and replication by gene deletion, by deleting proteins that interfere with the host immune response, or by introducing an immunopotentiating molecule such as GM-CSF into the coding sequence of the vaccine virus (e.g. E-041-1999). Each of the viruses replicates efficiently in vitro, and stability of the attenuation phenotype can be achieved for each of the viruses described.

There are multiple approaches to the development of these live attenuated intranasal vaccines for RSV and PIV, making it possible for different parties to pursue unique approaches to vaccine development. The following patents and patent applications are available for licensing; certain virus vaccine strains are also available for licensing.

RSV Portfolio

1. E-123-1992/0,1,2

Attenuated Respiratory Syncytial Virus Vaccine Compositions

U.S. Patent 5,922,326 (issued July 13, 1999); U.S. Patent 6,284,254 (issued September 4, 2001); U.S. Patent 5,882,651 (issued March 16, 1999); PCT/US93/03670 (publication WO 93/21310) and all corresponding foreign rights.

2. E-187-1995/0,1,2

Production of Infectious Respiratory Syncytial Virus From Cloned Nucleotide Sequences

U.S. Patent 6,264,957 (issued July 24, 2001); PCT/US96/15524 (publication WO 97/12032) and all corresponding foreign rights.

3. E-142-1996/0-4

Production of Attenuated Respiratory Syncytial Virus Vaccines From Cloned Nucleotide Sequences

U.S. Patent 5,993,824 (issued November 30, 1999); U.S. Patent 6,689,367 (issued February 10, 2004); USSN 09/444,067 (filed November 19, 1999); USSN 09/444,221 (filed November 19, 1999); PCT/US97/12269 (publication WO 98/02530) and all corresponding foreign rights.

4. E-040-1999/0

Production of Attenuated Negative Stranded RNA Virus Vaccines From Cloned Nucleotide Sequences

USSN 09/958,292 (filed January 1, 2002); PCT/US00/09695 (publication WO 00/61737) and all corresponding foreign rights.

5. E-041-1999/0

Production of Recombinant Respiratory Syncytial Viruses Expressing Immune Modulatory Molecules

U.S. Patent 6,699,476 (issued March 2, 2004); USSN 10/031,095 (filed January 9, 2002); USSN 10/754,895 (filed January 8, 2004); PCT/US00/19042 (publication WO 01/04271) and all corresponding foreign rights.

6. E-194-1999/0

Production of Attenuated Respiratory Syncytial Virus Vaccines Involving Modification of M2 ORF2

U.S. Patent 6,713,066 (issued March 30, 2004).

7. E-178-1999/0,1,2

Production of Attenuated, Human-Bovine Chimeric Respiratory Syncytial Virus Vaccines (E-178-1999/0,1,2)

USSN 09/602,212 (filed June 23, 2000); USSN 10/030,951 (filed January 8, 2002); USSN 10/704,116 (filed November 7, 2003); PCT/US00/17755 (publication WO 01/04335) and all corresponding foreign rights.

8. E-225-2000/0

Respiratory Syncytial Virus Vaccines Expressing Protective Antigens From Promotor-Proximal Genes

USSN 09/887,469 (filed June 22, 2001); USSN 10/312,191 (filed December 20, 2002); PCT/US01/20107 (publication WO 02/00693) and all corresponding foreign rights.

PIV Portfolio

1. E-089-1997/2,3,4,5,6

Production of Parainfluenza Virus From Cloned Nucleotide Sequences

USSN 09/424,628 (filed April 5, 2000), USSN 09/083,793 (filed May 22, 1998), USSN 09/586,479 (filed June 1, 2000), USSN 09/459,062 (filed December 10, 1999); USSN 09/350,831 (filed November 9, 1999); U.S. Patent 6,410,023 (issued June 4, 2002); U.S. Patent 6,410,023 (issued June 25, 2002); PCT/US98/10551 (publication 98/53078), PCT/US00/18523 (publication WO 01/03744) and all corresponding foreign rights.

2. E-099-1999/0,1

Use of Recombinant Parainfluenza Viruses (PIVs) as Vectors To Protect Against Infection and Disease Caused by PIV and Other Human Pathogens

USSN 09/733,692 (filed December 8, 2000), PCT/US00/33293 (publication WO 01/42445) and all corresponding foreign rights.

3. E-202-1999/0

Attenuated Human-Bovine Chimeric Parainfluenza Virus (PIV) Vaccines

USSN 10/030,544 (filed January 8, 2002); PCT/US00/17066 (publication WO 01/04320) and all corresponding foreign rights.

4. E-201-2000/0

Attenuated Human-Bovine Chimeric Parainfluenza Virus (PIV) Vaccines

USSN 09/900,112 (filed July 5, 2001).

5. E-280-2001/0

Recovery of Recombinant Human Parainfluenza Virus Type 1 (HPIV1) from cDNA and Use of Recombinant HPIV1 as Vaccines and Vectors to Protect Against Infection and Disease Caused by PIV and Other Human Pathogens

USSN 10/302,547 (filed November 21, 2002); PCT/US02/37688 (publication WO 03/043587) and all corresponding foreign rights.

6. E-092-2002/0

Recovery of Recombinant Human Parainfluenza Virus Type 2 (HPIV) From cDNA and Use of Recombinant HPIV2 in Immunogenic Compositions and as Vectors To Elicit Immune Responses Against PIV and Other Human Pathogens

USSN 10/667,141 (filed September 18, 2003); PCT/US03/29685 (publication WO 2004/027037).

HMPV Portfolio

1. E-093-2003/0-2

Recovery of Recombinant Human Metapneumovirus (HMPV) From cDNA and Use of Recombinant HMPV in Immunogenic Compositions and as Vectors To Elicit Immune Responses Against HMPV and Other Human Pathogens

USSN 60/451,119 (filed February 28, 2003); USSN 60/478,667 (filed June 13, 2003); PCT/US04/05881 (filed February 27, 2004); and USSN 10/789,400 (filed February 27, 2004).

Dated: September 7, 2004.

Steven M. Ferguson,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.