Association for Molecular Pathology v. U.S. Patent and Trademark Office

    By Kevin E. Noonan --

The lawsuit filed by plaintiffs and represented by lawyers from the American Civil Liberties Union and the Public Patent Foundation (PUBPAT) is easy to decry in the biotechnology patent community.  Patent Docs will provide a detailed explication of the complaint, including a discussion of its many falsehoods, misstatements and half-truths in a coming post.  However, before the complaint can be properly assessed, it is illustrative to consider the patents-in-suit and the claims expressly recited in the complaint as being unpatentable and unenforceable for violating 35 U.S.C. § 101, and Article I, section 8, clause 8, and the 1st and 14th Amendments to the Constitution.

The complaint identifies the following U.S. Patents:  Nos. 5,747,282; 5,837,492; 5,693,473; 5,709,999; 5,710,001; 5,753,441; and 6,033,857.  They are assigned to Myriad Genetics, the University of Utah Research Foundation, and the National Institutes of Health (the '282, '001 and '441 patents); Myriad Genetics, Centre de Recherche du Chul, and the Japanese Cancer Institute (the '473 and 999 patents); and Myriad Genetics, Endo Recherche, HCS R&D Ltd. Partnership, and the University of Pennsylvania (the '492 and '857 patents).  All but the '492 and '857 patents claim priority to an application filed August 12, 1994; all but the '473 patent (December 2014) and the '857 patent (March 2017) will expire (upon timely payment of maintenance fees) in 2015.

The claims targeted in the complaint illustrate, on the one hand, the plaintiffs' purpose:  to have a court rule on the patentability of genes per se.  This is shown by a consideration of the claims of the '282 patent expressly called out in the complaint:

1.  An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.

5.  An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

6.  An isolated DNA having at least 15 nucleotides of the DNA of claim 2.

7.  An isolated DNA selected from the group consisting of:
    (a)  a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having T at nucleotide position 4056;
    (b)  a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having an extra C at nucleotide position 5385;
    (c)  a DNA having the nucleotide sequence set forth in SEQ ID NO: 1 having G at nucleotide position 5443; and, (d) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having 11 base pairs at nucleotide positions 189-199 deleted.

20.  A method for screening potential cancer therapeutics which comprises:  growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic, growing said transformed eukaryotic host cell in the absence of said compound, determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and comparing the growth rate of said host cells, wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic.

However, the inclusion of claim 20 is curious, for several reasons.  First, this is a method of screening claim, which would encompass use of cells expressing a recombinant expression construct encoding an altered BRCA1 gene.  Such claims are recited in the '282 patent as compositions of matter (claims 8-13) but they are not named.  Moreover, this claim does not impact basic genetic research, overcoming restrictions of which are purportedly plaintiffs' purpose in filing the complaint.

The claims recited in the complaint for the remaining patents in suit are more consistent with this purported purpose:  for the '492 patent:

1.  An isolated DNA molecule coding for a BRCA2 polypeptide, said DNA molecule comprising a nucleic acid sequence encoding the amino acid sequence set forth in SEQ ID NO:2.

6.  An isolated DNA molecule coding for a mutated form of the BRCA2 polypeptide set forth in SEQ ID NO:2, wherein said mutated form of the BRCA2 polypeptide is associated with susceptibility to cancer.

7.  The isolated DNA molecule of claim 6, wherein the DNA molecule comprises a mutated nucleotide sequence set forth in SEQ ID NO:1.

(recombinant vector and transformed recombinant cell claims are not named); the '473 patent:

1.  An isolated DNA comprising an altered BRCA1 DNA having at least one of the alterations set forth in Tables 12A, 14, 18 or 19 with the proviso that the alteration is not a deletion of four nucleotides corresponding to base numbers 4184-4187 in SEQ. ID. NO:1.

(nucleic acid probe claims are not recited in the complaint); the '999 patent:

1.  A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1.

the '001 patent:

1.  A method for screening a tumor sample from a human subject for a somatic alteration in a BRCA1 gene in said tumor which comprises gene comparing a first sequence selected form the group consisting of a BRCA1 gene from said tumor sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made from mRNA from said tumor sample with a second sequence selected from the group consisting of BRCA1 gene from a nontumor sample of said subject, BRCA1 RNA from said nontumor sample and BRCA1 cDNA made from mRNA from said nontumor sample, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said tumor sample from the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said nontumor sample indicates a somatic alteration in the BRCA1 gene in said tumor sample.

(other method of diagnostic screening claims, including ones using antibodies to detect altered BRCA1 proteins, are not recited in the complaint); the '441 patent:

1.  A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject.

(other method of diagnostic screening claims, including ones using antibodies to detect altered BRCA1 proteins, are not recited in the complaint); and the '857 patent:

1.  A method for identifying a mutant BRCA2 nucleotide sequence in a suspected mutant BRCA2 allele which comprises comparing the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence, wherein a difference between the suspected mutant and the wild-type sequences identifies a mutant BRCA2 nucleotide sequence.

2.  A method for diagnosing a predisposition for breast cancer in a human subject which comprises comparing the germline sequence of the BRCA2 gene or the sequence of its mRNA in a tissue sample from said subject with the germline sequence of the wild-type BRCA2 gene or the sequence of its mRNA, wherein an alteration in the germline sequence of the BRCA2 gene or the sequence of its mRNA of the subject indicates a predisposition to said cancer.

The pattern of gene claims asserted (and not asserted) indicates that plaintiffs do not intend, for now, to pursue abrogation of the Supreme Court's Diamond v. Chakrabarty decision, insofar as that case held recombinant cells expressing heterologous proteins were patentable subject matter.  Accordingly, classical biotechnology -- providing cells for producing useful amounts of proteins such as erythropoietin, tissue plasminogen activator, insulin, and growth hormone, among many others -- are not likely to be at risk (unless plaintiffs amend their complaint to include such claims or the Supreme Court decides to revisit Chakrabarty).  However, gene patenting claims, including methods for using gene sequences for genetic diagnosis, are clearly in plaintiffs' sights.  The motivations for the lawsuit, and a more detailed analysis of the complaint, will be presented in future posts.

For additional information regarding this topic, please see:
• "Court Report," May 17, 2009
• "Court Report: Special Edition," May 13, 2009

Comments

[Pacific Reporter]

It looks like a lot of these claims fail under Bilski.

[Kevin E. Noonan]

Dear Pacific:

Not a lot - after all, Bilski is limited to method claims, and the composition of matter claims should be fine.

As for the method claims, I agree that under the Classen/Bilski line there is cause for concern (coupled with Metabolite), but the entire method of diagnosing type of claim is so questionable right now I wouldn't bet either way.

Thanks for the comment.

[6]

"Not a lot - after all, Bilski is limited to method claims,"

A commonly held misconception.

[Kevin E. Noonan]

Dear 6:

Enlighten us, please. How would you apply the Bilski decision to a composition of matter claim (should you ever have to examine one)?