[Federal Register Volume 77, Number 30 (Tuesday, February 14, 2012)]
[Notices]
[Pages 8263-8264]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-3410]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Prospective Grant of Exclusive License: The Development of Anti-
mesothelin Targeted Immunotoxins for the Treatment of Cancer

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 
CFR Part 404.7(a)(1)(i), that the National Institutes of Health, 
Department of Health and Human Services, is contemplating the grant of 
an exclusive patent license to practice the inventions embodied in US 
Patent application 61/535,668 entitled ``Pseudomonas Exotoxin A with 
Less Immunogenic B Cell Epitopes'' [HHS Ref. E-263-2011/0-US-01], US 
Patent application 61/495,085 entitled ``Pseudomonas Exotoxin A with 
Less Immunogenic T Cell Epitopes'' [HHS Ref. E-174-2011/0-US-01], US 
Patent application 61/483,531 entitled ``Recombinant Immunotoxin 
Targeting Mesothelin'' [HHS Ref. E-117-2011/0-US-01], U.S. Patent 
Application 61/241,620 entitled ``Development of an Immunotoxin in 
Which All B-Cell Epitopes Have Been Removed and Which Has High 
Cytotoxic Activity'' [HHS Ref. E-269-2009/0-US-01], U.S. Patent 
Application 60/969,929 entitled ``Deletions in Domain II of Pseudomonas 
Exotoxin A That Reduce Non-Specific Toxicity'' [HHS Ref. E-292-2007/0-
US-01], U.S. Patent Application 60/703,798 entitled ``Mutated 
Pseudomonas Exotoxins with Reduced Antigenicity'' [HHS Ref. E-262-2005/
0-US-01], U.S. Patent Application 60/160,071 entitled 
``Immunoconjugates Having High Binding Affinity'' [HHS Ref. E-139-1999/
0-US-01], U.S. Patent Application 60/067,175 entitled ``Antibodies, 
Including Fv Molecules, and Immunoconjugates Having High Binding 
Affinity for Mesothelin and Methods for Their Use'' [HHS Ref. E-021-
1998/0-US-01], U.S. Patent Application 60/010,166 entitled ``Molecular 
Cloning of Mesothelin, a Differentiation Antigen Present on 
Mesothelium, Mesotheliomas and Ovarian Cancers'' [HHS Ref. E-002-1996/
0-US-01], PCT Application PCT/US97/00224 entitled ``Mesothelin Antigen 
and Methods and Kits for Targeting It'' [HHS Ref. E-002-1996/1-PCT-01], 
U.S. Patent 5,747,654 entitled ``Recombinant Disulfide-Stabilized 
Polypeptide Fragments Having Binding Specificity'' [HHS Ref. E-163-
1993/0-US-01], PCT application PCT/US96/16327 entitled ``Immunotoxin 
Containing A Disulfide-Stabilized Antibody Fragment'' [HHS Ref. E-163-
1993/2-PCT-01], and all continuing applications and foreign 
counterparts, to Hoffman-La Roche, Inc. The patent rights in these 
inventions have been assigned to and/or exclusively licensed to the 
Government of the United States of America.
    The prospective exclusive license territory may be worldwide, and 
the field of use may be limited to:

    The use of anti-mesothelin targeted immunotoxins for the 
treatment of mesothelin-expressing cancers, wherein the immunotoxins 
have: (1) A targeting domain containing the complementary 
determining regions (CDR) of the SS1 antibody and (2) a Pseudomonas 
exotoxin A (``PE'') toxin domain that is (a) lysosomal protease 
resistant (PE-LR) and (b) lacks at least one major B-cell epitope 
due to the alteration of an amino acid. The immunotoxin may include 
additional alterations to B-cell and T-cell epitopes for reduction 
of immunogenicity, as well as a peptide linker sequence.


DATES: Only written comments and/or applications for a license which 
are received by the NIH Office of Technology Transfer on or before 
March 15, 2012 will be considered.

ADDRESSES: Requests for copies of the patent application, inquiries, 
comments, and other materials relating to the contemplated exclusive 
license should be directed to: David A. Lambertson, PhD, Senior 
Licensing and Patenting Manager, Office of Technology Transfer, 
National Institutes of Health, 6011 Executive Boulevard, Suite 325, 
Rockville, MD 20852-3804; Telephone: (301) 435-4632; Facsimile: (301) 
402-0220; Email: [email protected].

SUPPLEMENTARY INFORMATION: These inventions concern immunotoxins which 
are targeted to mesothelin-expressing cancer cells, and methods of

[[Page 8264]]

using the immunotoxins for the treatment of mesothelin-expressing 
cancers (such as mesothelioma, ovarian cancer and pancreatic cancer). 
The specific immunotoxin will have an antibody targeting domain that 
contains the CDRs of the antibody identified as SS1, which was invented 
at the NIH. The specific immunotoxin will also have a toxin domain 
derived from PE that is resistant to lysosomal proteases due to the 
deletion of a large portion of the exotoxin, and which lacks at least 
one major B-cell epitope due to the alteration an amino acid. 
Ultimately, the PE used in the immunotoxin may lack multiple B-cell 
epitopes, as well as multiple T-cell epitopes, in an effort to minimize 
immunogenicity.
    Alterations to the toxin that reduce immunogenicity improve the 
therapeutic value of the immunotoxin while maintaining its ability to 
trigger cell death. Since mesothelin is preferentially expressed on 
certain types of cancer cells, the immunotoxins selectively bind and 
kill only those cancer cells, allowing healthy, essential cells to 
remain unharmed. This results in an effective therapeutic strategy with 
fewer side effects.
    The prospective exclusive license will be royalty bearing and will 
comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR Part 
404.7. The prospective exclusive license may be granted unless the NIH 
receives written evidence and argument that establishes that the grant 
of the license would not be consistent with the requirements of 35 
U.S.C. 209 and 37 CFR Part 404.7 within thirty (30) days from the date 
of this published notice.
    Applications for a license in the field of use filed in response to 
this notice will be treated as objections to the grant of the 
contemplated exclusive license. Comments and objections submitted to 
this notice will not be made available for public inspection and, to 
the extent permitted by law, will not be released under the Freedom of 
Information Act, 5 U.S.C. 552.

     Dated: February 8, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development & Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-3410 Filed 2-13-12; 8:45 am]
BILLING CODE 4140-01-P