By Kevin E. Noonan --
Today
Myriad Genetics sued Ambry Genetics, Corp. in the District of Utah, Central Division
for patent infringement of ten patents relating to genetic diagnostic testing
(Case No. 2:13-cv-00640-RJS; complaint). Ambry
Genetics was one of the first companies to announce that it would provide genetic diagnostic testing for the BRCA 1 and BRCA 2
genes on the day the U.S. Supreme Court announced its decision in AMP v. Myriad Genetics on the question
of "whether human genes are patentable." Joining Myriad as plaintiffs are the
University of Utah Research Foundation, the Trustees of the University of
Pennsylvania, HSC Research and Development Limited Partnership, and
Endorecherche Inc.
The Complaint alleges that:
Defendant began offering its BRCA1 and BRCA2 analysis as part of its cancer testing menu on June 13, 2013. On information and belief, Defendant offers stand-alone tests comprising full gene sequencing and deletion/duplication analyses for the BRCA 1 and BRCA 2 genes. On information and belief, Defendant also offers full gene sequencing and deletion/duplication analyses for the BRCA 1 and BRCA 2 genes as part of multiple hereditary cancer panels that test cancer susceptibility using next-generation sequencing technology.
Defendant is infringing, contributing to the infringement of, and/or inducing others to infringe the '999 patent by making, manufacturing, promoting, marketing, advertising, distributing, offering for sale and selling and/or causing to be offered or sold certain BRCA1, BRCA2, BRCAPlus, BreastNext, OvaNext, and CancerNext products that infringe at least the following claim of [each of the patents in suit] literally and/or under the doctrine of equivalents for ten patents owned or licensed to Myriad.
The specific claims Myriad alleges are infringed include the following:
First Claim for Relief: U.S. Patent No. 5,709,999
Claim 6: 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, wherein a germline alteration is detected by amplifying all or part of a BRCA1 gene in said sample using a set of primers specific for a wild-type BRCA1 gene to produce amplified BRCA1 nucleic acids and sequencing the amplified BRCA1 nucleic acids.
Second Claim for Relief: U.S. Patent No. 5,747,282
Claim 6: An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1, and having at least 15 nucleotides of the DNA of claim 2.
Claim 16: A pair of single-stranded DNA primers for determination of a nucleotide sequence of a BRCA1 gene by a polymerase chin reaction, the sequence of said primers being derived from human chromosome 17q, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA having all or part of the sequence of the BRCA1 gene.
Claim 17: The pair of primers of claim 16 wherein said BRCA1 gene has the nucleotide sequence set forth in SEQ ID NO:1.
Third Claim for Relief: U.S. Patent No. 5,753,441
Claim 7: 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, wherein a germline nucleic acid sequence is compared by hybridizing a BRCA1 gene probe which specifically hybridizes to a BRCA1 allele to genomic DNA isolated from said sample and detecting the presence of a hybridization product wherein a presence of said product indicates the presence of said allele in the subject.
Claim 8: 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, wherein a germline nucleic acid sequence is compared by amplifying all or part of a BRCA1 gene from said sample using a set of primers to produce amplified nucleic acids and sequencing the amplified nucleic acid.
Claim 12: 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, wherein a germline nucleic acid sequence is compared by amplifying BRCA1 nucleic acids from said sample to produce amplified nucleic acids, hybridizing the amplified nucleic acids to a BRCA1 DNA probe specific for a BRCA1 allele and detecting the presence of a hybridization product, wherein the presence of said product indicates the presence of said allele in the subject.
Claim 23. 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 11 and 12 which comprises analyzing a sequence of the BRCA1 gene or BRCA1 RNA from a human sample or analyzing the sequence of BRCA1 CDNA made from mRNA from said sample, wherein a germline alteration is detected by amplifying all or part of a BRCA1 gene in said sample using a set of primers to produce amplified nucleic acids and sequencing the amplified nucleic acids.
Claim 26. 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 11 and 12 which comprises analyzing a sequence of the BRCA1 gene or BRCA1 RNA from a human sample or analyzing the sequence of BRCA1 CDNA made from mRNA from said sample, wherein a germline alteration is detected by amplifying BRCA1 gene nucleic acids in said sample, hybridizing the amplified nucleic acids to a BRCA1 DNA probe specific for one of said alterations and detecting the presence of a hybridization product, wherein the presence of said product indicates the presence of said alteration.
Fourth Claim for Relief: U.S. Patent No. 5,837,492
Claim 29. A pair of single-stranded DNA primers of at least 15 nucleotides in length for determination of the nucleotide sequence of a BRCA2 gene by a polymerase chain reaction, the sequence of said primers being isolated from human chromosome 13, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA comprising all or at least 15 contiguous nucleotides of the BRCA2 gene.
Claim 30. The pair of primers of claim 29 wherein said BRCA2 gene has the nucleotide sequence set forth in SEQ ID NO:1.
Fifth Claim for Relief: U.S. Patent No. 6,033,857
Claim 4. 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, wherein the detection in the alteration in the germline sequence is determined by an assay selected from the group consisting of (a) observing shifts in electrophoretic mobility of single-stranded DNA on non-denaturing polyacrylamide gels, (b) hybridizing a BRCA2 gene probe to genomic DNA isolated from said tissue sample, (c) hybridizing an allele-specific probe to genomic DNA of the tissue sample, (d) amplifying all or part of the BRCA2 gene from said tissue sample to produce an amplified sequence and sequencing the amplified sequence, (e) amplifying all or part of the BRCA2 gene from said tissue sample using primers for a specific BRCA2 mutant allele, (f) molecularly cloning all or part of the BRCA2 gene from said tissue sample to produce a cloned sequence and sequencing the cloned sequence, (g) identifying a mismatch between (1) a BRCA2 gene or a BRCA2 mRNA isolated from said tissue sample, and (2) a nucleic acid probe complementary to the human wild-type BRCA2 gene sequence, when molecules (1) and (2) are hybridized to each other to form a duplex, (h) amplification of BRCA2 gene sequences in said tissue sample and hybridization of the amplified sequences to nucleic acid probes which comprise wild-type BRCA2 gene sequences, (i) amplification of BRCA2 gene sequences in said tissue sample and hybridization of the amplified sequences to nucleic acid probes which comprise mutant BRCA2 gene sequences, (j) screening for a deletion mutation in said tissue sample, (k) screening for a point mutation in said tissue sample, (l) screening for an insertion mutation in said tissue sample, (m) in situ hybridization of the BRCA2 gene of said tissue sample with nucleic acid probes which comprise the BRCA2 gene.
Sixth Claim for Relief: U.S. Patent No. 5,654,155
Claim 2. A method
of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
associated with breast or ovarian cancer comprising:
a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
b) sequencing said amplified fragment by dideoxy
sequencing;
c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
d) comparing the sequence of said amplified DNA to
the sequence of SEQ. ID. NO: 1;
e) determining the presence or absence of each of
the following polymorphic variations in said individual's BRCA1 coding
sequence:
AGC and ACT at position 2201, TTG and CTG at
position 2430, CCG and CTG at position
2731, GAA and GGA at position 3232, AAA
and AGA at position 3667, TCT and TCC at position 4427, and ACT and GGT at
position 4956;
f) determining any sequence differences between
said individual's BRCA1 coding sequences and SEQ. ID. NO: 1 wherein the
presence of any of the said polymorphic variations and the absence of a
polymorphism outside of positions 2201, 2430, 2731, 3232, 3667, 4427, and 4956,
is correlated with an absence of increased genetic susceptibility to breast or
ovarian cancer resulting from a BRCA1 mutation in the BRCA1 coding sequence.
Claim 3. A method according to claim 2 wherein said oligonucleotide primer is labeled with a radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent label or an enzyme label
Claim 4. A method
of detecting an increased genetic susceptibility to breast and ovarian cancer
in an individual resulting from the presence of a mutation in the BRCA1 coding
sequence, comprising:
a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
b) sequencing said amplified fragment by dideoxy
sequencing;
c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
d) comparing the sequence of said amplified DNA to
the sequence of SEQ. ID. NO: 1;
e) determining any sequence differences between
said individual's BRCA1 coding sequences and SEQ. ID. NO: 1 to determine the
presence or absence of polymorphisms in said individual's BRCA coding sequences
wherein a polymorphism which is not any of the following:
AGC or AGT at position 2201, TTG or CTG at position
2430, CCG or CTG at position 2731, GAA or GGA at position 3232, AAA or AGA at
position 3667, TCT or TCC at position 4427, and AGT or GGT at position 4956;
is correlated with the potential of increased
genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
mutation in the BRCA1 coding sequence.
Seventh Claim for Relief: U.S. Patent No. 5,750,400
Claim 2. A method
of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
associated with ovarian or breast cancer disease, comprising:
(a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
(b) sequencing said amplified DNA fragment by
dideoxy sequencing;
(c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
(d) comparing the sequence of said amplified DNA
fragment to a BRCA1(omi) DNA sequence selected from the group
consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
NO: 5;
(e) determining the presence or absence of each of
the following polymorphic variations in said individual's BRCA1 coding
sequence:
(i) C and T at position 2201,
(ii) T and C at position 2430,
(iii) C and T at position 2731,
(iv) A and G at position 3232,
(v) A and G at position 3667,
(vi) T and C at position 4427, and
(vii) A and G at position 4956;
(f) determining any sequence differences between
said individual's BRCA1 coding sequences and a BRCA1(omi) DNA
sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
5, SEQ ID NO: 3 and SEQ ID NO: 5, wherein the presence of said polymorphic
variations and the absence of a variation outside of positions 2201, 2430,
2731, 3232, 3667, 4427 and 4956 is correlated with an absence of increased
genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
mutation in the BRCA1 coding sequence.
Claim 3. A method
of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
associated with ovarian or breast cancer disease, comprising:
(a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
(b) sequencing said amplified DNA fragment by
dideoxy sequencing;
(c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
(d) comparing the sequence of said amplified DNA
fragment to a BRCA1(omi)) DNA sequence selected from the group
consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
NO: 5;
(e) determining the presence or absence of each of
the following polymorphic variations in said individual's BRCA1 coding
sequence:
(i) C and T at position 2201,
(ii) T and C at position 2430,
(iii) C an d T at position 2731,
(iv) A and G at position 3232,
(v) A and G at position 3667,
(vi) T and C at position 4427, and
(vii) A and G at position 4956; and
(f) determining any sequence differences between
said individual's BRCA1 coding sequences and a BRCA1(omi) DNA
sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
5, SEQ ID NO: 3 and SEQ ID NO: 5, wherein the presence of said polymorphic
variations and the absence of a variation outside of positions 2201, 2430,
2731, 3232, 3667, 4427 and 4956 is correlated with an absence of increased
genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
mutation in the BRCA1 coding sequence;
wherein codon variations occur at the following
frequencies, respectively, in a Caucasian population of individuals with no
family history of breast or ovarian cancer:
(i) at position 2201, C and T occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
(ii) at position 2430, T and C occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
(iii) at position 2731, C and T occur at
frequencies from about 25 to about 35%, and from about 65 to about 75%,
respectively;
(iv) at position 3232, A and G occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
(v) at position 3667, A and G occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
(vi) at position 4427, T and C occur at frequencies
from about 45 to about 55%, and from about 45 to about 55%, respectively; and
(vii) at position 4956, A and G occur at
frequencies from about 35 to about 45%, and from about 55 to about 65%,
respectively.
Claim 4. A method according to claims 2 or 3, wherein said oligonucleotide primer is labeled with a radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent label, or an enzyme label.
Claim 5. A method
of detecting an increased genetic susceptibility to breast and ovarian cancer
in an individual resulting from the presence of a mutation in the BRCA1 coding
sequence, comprising:
(a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
(b) sequencing said amplified DNA fragment by
dideoxy sequencing;
(c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
(d) comparing the sequence of said amplified DNA
fragment to a BRCA1(omi) DNA sequence selected from the group
consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
NO: 5;
(e) determining any sequence differences between
said individual's BRCA1 coding sequences and a BRCA1(omi) DNA
sequence selected from the group consisting of: SEQ. ID. NO.: 1 together with
SEQ ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together
with SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID
NO: 5, SEQ ID NO: 3 and SEQ ID NO: 5 in order to determine the presence or
absence of base changes in said individual's BRCA1 coding sequence wherein a
base change which is not any one of the following:
(i) C and T at position 2201,
(ii) T and C at position 2430,
(iii) C and T at position 2731,
(iv) A and G at position 3232,
(v) A and G at position 3667,
(vi) T and C at position 4427, and
(vii) A and G at position 4956, is correlated with
the potential of increased genetic susceptibility to breast or ovarian cancer
resulting from a BRCA1 mutation in the BRCA1 coding sequence.
Claim 6. A method
of detecting an increased genetic susceptibility to breast and ovarian cancer
in an individual resulting from the presence of a mutation in the BRCA1 coding
sequence, comprising:
(a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
(b) sequencing said amplified DNA fragment by
dideoxy sequencing;
(c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
(d) comparing the sequence of said amplified DNA
fragment to a BRCA1(omi) DNA sequence selected from the group
consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
NO: 5;
(e) determining any sequence differences between
said individual's BRCA1 coding sequences and a BRCA1(omi) DNA
sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
5, SEQ ID NO: 3 and SEQ ID NO: 5 in order to determine the presence or absence
of base changes in said individual's BRCA1 coding sequence wherein a base
change which is not any one of the following:
(i) C and T at position 2201,
(ii) T and C at position 2430,
(iii) C and T at position 2731,
(iv) A and G at position 3232,
(v) A and G at position 3667,
(vi) T and C at position 4427, and
(vii) A and G at position 4956, is correlated with
the potential of increased genetic susceptibility to breast or ovarian cancer
resulting from a BRCA1 mutation in the BRCA1 coding sequence, wherein codon
variations occur at the following frequencies, respectively, in a Caucasian
population of individuals with no family history of breast or ovarian cancer:
(i) at position 2201, C and T occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
(ii) at position 2430, T and C occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
(iii) at position 2731, C and T occur at
frequencies from about 25 to about 35%, and from about 65 to about 75%,
respectively;
(iv) at position 3232, A and G occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
(v) at position 3667, A and G occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
(vi) at position 4427, T and C occur at frequencies
from about 45 to about 55%, and from about 45 to about 55%, respectively; and
(vii) at position 4956, A and G occur at
frequencies from about 35 to about 45%, and from about 55 to about 65%,
respectively.
Claim 7. A method according to claims 5 or 6, wherein said oligonucleotide primer is labeled with a radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent label, or an enzyme label.
Eighth Claim for Relief: U.S. Patent No. 6,051,379
Claim 32. A
method of detecting a predisposition or higher susceptibility to cancer in an
individual, comprising:
(a) digesting DNA from an individual to obtain DNA
fragments;
(b) separating said DNA fragments;
(c) detecting a DNA fragment containing nucleotide
number 2192, 3772, 5193, 5374, 6495 or 6909 of the BRCA2 gene sequence or a
sequence variation at nucleotide number 2192, 3772, 5193, 5374, 6495 or 6909 of
the BRCA2 gene sequence by sequencing;
(d) comparing the sequence of said fragment with
the BRCA2 gene sequence to determine the presence or absence of a sequence
variation at nucleotide number 2192, 3772, 5193, 5374, 6495 or 6909, wherein
the presence of a sequence variation indicates a predisposition or higher
susceptibility to cancer.
Claim 33. A method according to claim 32 further comprising amplifying said DNA fragments prior to the detecting step (c).
Ninth Claim for Relief: U.S. Patent No. 6,951,721
Claim 5. A method for determining an omi haplotype of a human BRCA1 gene comprising: (a) determining the nucleotide sequence of the BRCA1 gene or fragment thereof from at least one female individual with a family history which indicates a predisposition to breast cancer, (b) comparing the determined nucleotide sequence from said female individual to SEQ ID NO: 263, and (c) determining the presence of the following nucleotide variations: thymine at nucleotides 2201 and 2731, cytosine at nucleotides 2430 and 4427, and guanine at nucleotides 3232, 3667 and 4956, wherein the presence of the nucleotide variations in the determined nucleotide sequence indicates the omi1 haplotype, further comprising comparing the determined nucleotide sequence to SEQ ID NO: 265.
Tenth Claim for Relief: U.S. Patent No. 7,250,497
Claims 3, 4, 5, 6, 7, 8, 11, 14, 17, 18, 19
[Claim 1. An isolated nucleic acid comprising SEQ ID NO:6, and the complement thereof.
Claim 2. The isolated nucleic acid of claim 1, wherein said isolated nucleic acid comprises SEQ ID NO:37, or the complement thereof.]
Claim 3. A method of making the isolated nucleic acid of claim 2 comprising amplifying genomic DNA isolated from a sample obtained from a human patient.
Claim 4. A method of making the isolated nucleic acid of claim 1 comprising amplifying genomic DNA isolated from a sample obtained from a human patient.
Claim 5. The method of claim 4, wherein said sample is a blood sample.
Claim 6. The method of claim 4, wherein said amplification is by the polymerase chain reaction.
Claim 7. The method of claim 4, wherein said patient is being evaluated for an enhanced risk of cancer.
Claim 8. The method of claim 4, wherein said cancer is breast or ovarian cancer.
Claim 11. A method of making the isolated nucleic acid of claim 9 comprising amplifying genomic DNA isolated from a sample obtained from a human patient.
Claim 14. A method of making the isolated nucleic acid of claim 12 comprising amplifying genomic DNA isolated from a sample obtained from a human patient.
Claim 17. A method of making the isolated nucleic acid of claim 15 comprising amplifying genomic DNA isolated from a sample obtained from a human patient.
Claim 18. The isolated nucleic acid of claim 1, wherein said isolated nucleic acid comprises SEQ ID NO:41, or the complement thereof.
Claim 19. A method of making the isolated nucleic acid of claim 18 comprising amplifying genomic DNA isolated from a sample obtained from a human patient.
These method claims differ from the claims invalidated by the District Court in the Myriad case and affirmed by the Federal Circuit, which recited as limitations merely "comparing" an individual's BRCA gene sequence with the "normal" one, and thus Myriad is less likely to be estopped from asserting these claims against Ambry.
Myriad's Relief Requested in its complaint includes
judgment of patent infringement, an injunction, an accounting and damages, delivery for destruction of all "products"
that infringe any of the asserted claims, a finding of willful infringement,
and a request for attorneys' fees, enhanced damages and costs of suit. Myriad also demands a jury trial.
As has been discussed in earlier posts, some of these claims (e.g., directed to oligonucleotides) may be subject to invalidation on novelty grounds (see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims"). In addition, not all assignees are named in the complaint (most notably the U.S. Government "as represented by the Secretary of Health") and insofar as any of them are adjudged to be indispensible parties, any unwillingness to be joined might cause Myriad procedural difficulties. But it is significant that Myriad has decided to assert these patents, and its continued ability to do so illustrates one of the generally unappreciated aspects of the Myriad case. Plaintiffs in that case and their supporters, the ACLU and Public Patent Foundation, chose the claims against which to assert their challenge to the validity of Myriad's patents. Which means, of course, that they chose not to challenge the claims Myriad is now asserting, leaving the plaintiffs (including breast cancer patients) without the full and complete remedy they no doubt were promised and that the press seems to believe the Supreme Court's June 13 decision gave them (see "Reaction to Supreme Court's Decision in AMP v. Myriad" and "Does the Myriad Decision Presage a Golden Age of Patent-Free Personalized Medicine?"). Instead, plaintiffs challenged claims to isolated DNA (characterized as "genes"), even though such claims are not infringed by the practice of modern genetic diagnostic methods. The result of these strategic (and ultimately political or at least public-relations focused) decisions is that Myriad owns or has licensed patents that presumptively preclude Ambry Genetics or any other provider from offering BRCA gene-directed genetic diagnostic tests until these patents expire in the next few years. In short, the parties are in exactly the same position that existed prior to the Myriad suit. While this outcome should have been expected, it raises doubts about the consensus narrative of what "everybody knows" this case was all about.
Really nice post, Kevin.
The claims are mainly the PCR-based method claims (plus the claims in the GeneLogic and OncorMed patents that include all sorts of methods), although the complaint does include the likely-invalid 15-mer claim 6 of '282.
It is indeed interesting that NIH is not included, as Myriad signed an agreement in Feb 1995 that includes obligatory consultation with NIH and a 90-day "no litigation" clause. I do not know if that agreement is still in effect (it is part of the '282 patent file wrapper: http://duke.edu/~kgm4/Myriad282/utah%20nih%20agreement.pdf). If it is, it is surprising this suit would be filed well before that 90-day no-litigation deadline and before formally notifying Ambry, which appears to be an obligatory initial action under the agreement.
If this goes to trial, perhaps we'll begin to finally learn what some of these claims mean. But for Myriad to prevail, they have to at least mean "if we find a gene, we get exclusive rights to PCR amplify that gene for the term of the patent" (including if segments from that gene are a minority among segments from many other genes being PCR-amplified and sequenced).
And perhaps you can edify us about the legal strategy. They have sued the weakest and smallest of the competitors, which of course they can do. But I'm wondering why, aside from perhaps wanting to shoot across the bow of others. Or is this likely just the first of several suits? And the only effective remedy here would be an injunction, but given the history of this case and in light of eBay v MercExchange, that seems a dicey. Is this perhaps just the opening phase of Myriad out-licensing? I would think this litigation could in fact force Myriad into just that.
We'll see.
Posted by: Bob Cook-Deegan | July 10, 2013 at 02:49 AM
Two other points.
First, I know that some of the labs were well aware of the unchallenged claims in AMP v Myriad, so it's not quite true their decision to enter the market is an unwitting risk. I presume their (supremely competent, in at least one case) lawyers have thought through this.
Second, I was surprised that Myriad brought BRCA2 into their infringement allegations. Their BRCA2 patents seem quite vulnerable, given that USPTO never declared a BRCA2 interference, so far as I can tell, and yet Myriad scientists openly acknowledge that they "got wind" of Stratton's work and rushed to do their own patent. If that was because a Nature reviewer shared the information about a pending publication, wouldn't those OncorMed and Myriad/Utah BRCA2 patents be on very thin ice?
Posted by: Bob Cook-Deegan | July 10, 2013 at 03:31 AM
"And perhaps you can edify us about the legal strategy. They have sued the weakest and smallest of the competitors, which of course they can do. But I'm wondering why, aside from perhaps wanting to shoot across the bow of others."
Bob,
The strategy is very obvious to me. What Myriad wants to do is get, as quick as possible, is a validity/infringement judgment ruling early, and the best way to do that is against the weaker/smaller competitors. With such a judgment in hand, Myriad can then push against the bigger/stronger competitors, including going for a preliminary injunction (success of which often requires having at least prior validity ruling and possibly prior infringement ruling). I could be wrong on the strategy, but that's what it looks like to me what Myriad is doing.
Posted by: EG | July 10, 2013 at 08:16 AM
A similar question was posed with Monsanto - why would they pick on a small-time independent 80+ year old farmer who obviously does not have deep pockets...
Posted by: Skeptical | July 10, 2013 at 09:23 AM
Dear Bob:
EG is correct that some litigants will pick a smaller infringer, typically with a view towards licensing as you propose. Myriad could be working on a licensing structure that would require Ambry or other genetics diagnostic test providers to obtain a Myriad test result from any prospective client, which would deal with the "second opinion" issue (and could preclude or at least forestall Congressional action if and when the long-awaited "second opinion" study is released).
And while I have no reason to question the competancy of Ambry's legal counsel, I'm not sure anyone can give advice with any certainty in this area, in view of the "know it when we see it" standard that the Supreme Court has adopted regarding testing.
I suspect the BRCA 2 claims are in the case because Ambry said it would provide this testing, and if it comes to trial I would expect Ambry to assert prior invenetion under 102(g). Because we don't know the facts it is impossible to predict whether Myriad will prevail on priority to the claims at issue directed to BRCA 2.
Thanks for the comments.
Posted by: Kevin E. Noonan | July 10, 2013 at 11:18 AM
Dear Skeptical:
I don't know about Farmer Bowman, but in earlier cases the "small farmer" was producing soybeans from tens of thousands of acres. This may be a remnant of changes from the days of the family farm, where modern technology and the economic downturn on farms in the 1980's permitted small farmers to increase their yields and holdings to levels that would not satisfy most peoples' definitions of "small."
Or maybe Monsanto had other strategic reasons (other than the "pick on the little guy" approach) that were relevant to the decision.
After all, Monsanto also sued DuPont/Pioneer and got a $1 billion judgment against them, so the company is not afriad to take on bigger opponents when need be.
Thanks for the comment.
Posted by: Kevin E. Noonan | July 10, 2013 at 11:27 AM
Next up, Gene by Gene Ltd. - 7/10/2013
Posted by: Paul San Quentin | July 10, 2013 at 02:46 PM
Thanks, Paul - see next post
Posted by: Kevin E. Noonan | July 10, 2013 at 07:11 PM
Kevin: "[P]laintiffs challenged claims to isolated DNA (characterized as "genes"), even though such claims are not infringed by the practice of modern genetic diagnostic methods."
Right, but according to Myriad, each of the primers -- in fact, every nucleic acid primer that is not modified in some specific (claimed) manner -- is ineligible in view of Myriad.
Do you really think the courts are going to find that you can turn ineligible subject matter into an eligible claim merely by reciting another ineligible composition? Can I claim a composition consisting of, say, an ineligible probe and an ineligible complementary chromosomal sequence, thereby preventing someone from using that probe to bind to the sequence (which I was the first to discover, of course)? What's the difference?
Posted by: Huong W. | July 10, 2013 at 09:31 PM
Dear Huong:
You can certainly take an unpatentably reagent and perform a test that you patent. What's the difference?
Posted by: Kevin E. Noonan | July 11, 2013 at 03:51 PM
I would hazard a guess that a product of nature judicial exception does not rule out the ability to obtain a PROCESS patent for obtaining an end result (the product of nature), that itself is not eligible for patenting.
Come up with a new way to make water? Great - have a patent on the process.
Want a patent on water? Sorry, no.
And yes I used water as a readily identifiable item - I could have used "sdfghala" and postulated that "sdfghala" was a product of nature, though just discovered (and purposefully echoing Chakrabarty at that).
Posted by: Skeptical | July 11, 2013 at 04:34 PM
Dear Skeptical:
You don't need to guess - just read the Cochrane v. Badische Anilin Soda Fabrik case
Posted by: Kevin E. Noonan | July 11, 2013 at 08:40 PM
Dr. Noonan,
The 'hazard a guess' was rhetorical.
Posted by: Skeptical | July 12, 2013 at 06:44 AM
Sorry, Skeptical - but thanks for helping to enlighten others
Posted by: Kevin E. Noonan | July 12, 2013 at 05:19 PM