Bertina et alv.Reitsma

Board of Patent Appeals and Interferences

Feb 21, 2001

08454353 (B.P.A.I. Feb. 21, 2001)

Paper No. 112
THIS OPINION IS NOT BINDING PRECEDENT OF THE BOARD.
35 U.S.C. § 135(c) Notice: Failure to file a copy of any agreement regarding the termination of this proceeding may
render the agreement and any resulting patents unenforceab le. See section 135(c) and 37 CFR § 1.661 for more details.
Trial Section Merits Panel
BOX INTERFERENCE
WASHINGTO N DC 20231
Telephone: 703-308-9797
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UNITED STATES PATENT AND TRADEMARK OFFICE
_______________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_______________
JOHN H. GRIFFIN and JUDITH GREENGARD
(08/410,488),
Junior Party,
v.
ROGIER M. BERTINA and PIETER H. REITSMA
(08/454,353),
Senior Party.
_______________
Interference No. 104,021
_______________
Before SCHAFER, LEE, and TORCZON, Administrative Patent Judges.
TORCZON, Administrative Patent Judge.
JUDGMENT
(PURSUANT TO 37 CFR § 1.658)
INTRODUCTION
After consideration of the briefs, the evidence, and the oral argument on priority, we
conclude from the preponderance of the facts before us that junior party Griffin has failed to
establish a reduction to practice before senior party Bertina's effective filing date.
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Paper No. 112
1
No evidence w as presented regarding the kit altern ative in the count, so this opinion will focus on the method
alternative.
2
Claim 80, which the examiner has deemed to be unpatentable, is:
A kit for diagnosing an inc reased risk from thr ombosis or a genetic de fect causing throm bosis
comprising a forward and a reverse primer that are capable of amplifying codon 506 within EXON 10
of the human Factor V gene.
BACKGROUND
The count and involved claims
After decision on preliminary motions (Paper No. 70), the interference was redeclared
(Paper No. 71) with the following count:
A method according to claim 62 of the Bertina application
OR
A kit according to claim 81 of the Bertina application.1
Claims 62 and 81 of the Bertina application are as follows
62. A method for diagnosing an increased risk for thrombosis of a genetic
defect causing thrombosis comprising the steps of:
(A) obtaining, from a test subject, test nucleic acid comprising codon 506
within EXON 10 of the human Factor V gene; and
(B) assaying for the presence of a point mutation in the nucleotides of
codon 506 within EXON 10 of the human Factor V gene, wherein said
point mutation correlates to a decrease in the degree of inactivation of
human Factor V and/or human Factor Va by activated protein C,
wherein the presence of said point mutation in said test nucleic acid indicates an
increased risk for thrombosis or a genetic defect causing thrombosis.
81. The kit of claim 80,[2] wherein said forward primer is selected from the
group consisting of SEQ ID NO:4, SEQ ID NO:9, and SEQ ID NO:11, and said
reverse primer is selected from the group consisting of SEQ ID NO:5, SEQ ID
NO:10 and SEQ ID NO:14.
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3
The Griffin record is paginated as "Gxxx", where "xxx" is a three-digit number. Griffin exhibits are
numbered starting with "1001". The Bertina record is paginated "Bxxxx", where "xxxx" is a four-digit number. Bertina
exhibits are numbered starting with "2001".
The count requires an appreciation of the significance of a mutation at codon 506 within
exon 10 of the human Factor V gene to the diagnosis of an increased risk of thrombosis due to a
genetic defect.
Priority cases
Junior party Griffin filed a principal brief on priority (Paper No. 94), a reply brief (Paper
No. 99), and supporting exhibits. Bertina filed an opposition brief (Paper No. 97) and supporting
exhibits, but elected to rely on its accorded benefit date rather than put on a separate priority case
(Paper No. 96).3
Counsel for each party appeared for oral argument and ably presented the views of his
client.
DISCUSSION
The only issue presented for decision is whether junior party Griffin successfully reduced
to practice the invention of the count before senior party Bertina's earliest accorded benefit date
(Paper No. 94 at 4; Paper No. 97 at 4 & 5). Reduction to practice requires the production and
recognition of an embodiment meeting all limitations of the count and the recognition of a
specific practical utility for the invention. Estee Lauder Inc. v. L'Oreal, S.A., 129 F.3d 588, 593,
44 USPQ2d 1610, 1614 (Fed. Cir. 1997). Recognition of the invention in the count cannot be
established retroactively: it must be contemporaneous with the alleged priority date. E.g., Estee
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Lauder, 129 F.3d at 593-94, 44 USPQ2d at 1614 (citing Breen v. Henshaw, 472 F.2d 1398, 1401,
176 USPQ 519, 521 (CCPA 1973)).
Facts
A junior party in an interference between co-pending applications must establish priority
by a preponderance of evidence. Cooper v. Goldfarb, 154 F.3d 1321, 1327, 47 USPQ2d 1896,
1900 (Fed. Cir. 1998). Inventor testimony must be independently corroborated. Cooper,
154 F.3d at 1330, 47 USPQ2d at 1903.
F1. John H. Griffin (Dr. Griffin) and Judith S. Greengard (Dr. Greengard) are the
named inventors of Griffin's involved 07/410,488 application.
F2. Griffin's involved application was filed 24 March 1995. Griffin has not been
accorded benefit of any other application.
F3. Bertina's involved 08/454,353 application was filed 6 June 1995. Bertina was
accorded the benefit (Paper No. 1 at 41) of Patent Cooperation Treaty (PCT) application
PCT/EP95/00553, filed 14 February 1995, and of European patent application 94-200377.3, filed
14 February 1994 (the critical date).
F4. Griffin's case is that the Griffin inventors (Drs. Griffin and Greengard) identified
the codon 506 mutation as a genetic cause of activated protein C (APC) resistance, which
increases the risk of thrombosis, no later than 2 December 1993 (Griffin's alleged priority date)
(Paper No. 94 at 15).
F5. The codon 506 point mutation is an A for G substitution at the middle nucleotide
of the codon (Paper No. 94 at 15 n.2). This mutation is also identified as nucleotide 205 of
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exon 10 or as nucleotide 1691 (nt 1691) of the complementary DNA (cDNA) (Paper No. 94 at 15
n.2). This mutation results in a substitution of glutamine (Q) for arginine (R) at amino acid 506
(hence, the nomenclature "R506Q" in Paper No. 70).
F6. Drs. Griffin and Greengard testified that in the summer of 1993 they were seeking
mutations in Factor V protein as a cause or contributing cause of APC resistance (G019-20 &
G028-29).
F7. In July 1993, Drs. Griffin and Greengard were billed for the production of the
following eight twenty-base oligonucleotides (G038; Exh. 1029):
FV1 made 07-27-93
FV2 made 07-27-93
FV3 made 07-27-93
FV4 made 07-27-93
FV5 made 07-27-93
FV6 made 07-27-93
FV7 made 07-27-93
FV8A made 07-27-93
F8. The only use of such primers apparent from the record is the amplification of the
DNA of Factor V cleavage sites (e.g., G028; Exh. 1001).
F9. As of 28 July 1993, Dr. Greengard intended to use the primers to examine
Factor V from APC-resistant patients (Exh. 1001).
F10. By 4 August 1993, Xiao Xu, a colleague of Drs. Griffin and Greengard, had
identified "best" conditions for amplifying the primers (G032; Exh. 1020).
F11. On 23 August 1993, the Centers for Disease Control and Prevention shipped to
Dr. Griffin stabilized blood samples from the "S" family (G042).
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4
Griffin's record is inconsistent in its labeling of primers. Some primers, such as FV8 variously include either
an "A" or "a" designation. We assume that, for the purposes of our decision FV8, FV8A, and FV8a are the same. The
critical sequencing gels in the record were made using only the FV7 primer in any case.
5
The primers sometimes have an "A" or "a" added to their names. If this addition indicates a different primer,
then even more primers may have been tested.
6
Exhibit 1025 is an enlarged and labeled portion of Exhibit 1023.
7
Exhibit 1026 is an enlarged and labeled portion of Exhibit 1024.
F12. Jose Fernandez, another colleague of the Griffin inventors, performed a
coagulation assay of the S family blood and determined that a sample from S family member
"LS" exhibited APC resistance, while a sample from S family member "AS" did not (G035-36;
Exhs. 1030 & 1031).
F13. On 27 August 1993, Xu amplified DNA samples from S family members,
including AS and LS, using the eight primers (FV1-FV8A)4 as well as additional primers (FV9-
FV12)5 (G032; Exh. 1021).
F14. On 18 October 1993, Xu prepared sequencing gels (Exh. 1023)6 for LS and for AS
(G033; Exh. 1022) using the FV7 primer, among others. The record copy of the 18 October 1993
gel contains no indication that the nt 1691 point mutation was recognized. Exhibit 1023
indicates that AS only has a band in the G column for nucleotide 1691.
F15. On 25 October 1993, Xu again prepared sequencing gels (Exh. 1024)7 for LS and
for AS (Exh. 1022 at 3) using the FV7 primer, among others. The record copy of the 25 October
1993 gel contains no indication that the nt 1691 point mutation was recognized. Exhibit 1024
indicates that AS only has a band in the G column for nucleotide 1691.
F16. The gels lanes are in sets of four for A, C, G, and T, respectively, running left to
right. The sequence should be read up from the bottom.
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8
In summary, Bertina's se mi-independe nt, experience d expert (van G emen) testified tha t the gels are too
unclear to read with certainty. Griffin's high ly experienced expert, who works f or Griffin's real par ty-in-interest,
(Sutcliffe) testified that the gels were typical of 1993 sequencing gels and were readily understandable although they
might be difficult for one unskilled to read. Gr iffin has not pointed us to any testimony on the level of skill of the G riffin
inventors at reading sequencing gels or any details about how they went about deciphering the gels.
9
Griffin's expert Sutcliffe distinguished between being confident that he "knew" the sequence and being
sufficiently certain to publish the result (G179).
F17. Whether the FV7 sequencing gels clearly show the nt 1691 point mutation for LS
is a point of considerable contention.8 We assume, without deciding, that Drs. Griffin and
Greengard could have read the sequencing gels and identified the nt 1691 point mutation with
reasonable9 certainty.
F18. Dr. Griffin testified (G030):
15. I recall that I discussed with Dr. Judy Greengard prior to
our weekly laboratory meeting on December 2, 1993, her findings of a G
to A nucleotide mutation at position [1691] of [LS's] genomic DNA.
F19. Dr. Greengard testified (G023):
25. I read the sequencing films, GRIFFIN EXHIBITS
1023 and 1024, after the Thanksgiving holiday in November 1993, but
before our weekly Laboratory Meeting which was held on Tuesday,
December 2, 1993.
26. During my reading of these sequencing films, GRIFFIN
EXHIBITS 1023 and 1024, I had noted a G to A mutation in the genomic
DNA of LS at nucleotide position [1691] and discussed this finding with
Dr. Griffin prior to the aforementioned weekly Laboratory Meeting on
December 2, 1993.
F20. Fernandez testified (G036):
9. That prior [to] going to the American Society of
Hematology meeting in St. Louis, MO held December 3 to December 7,
1993, he [Fernandez] learned from Dr. Greengard that a G to A mutation
had been found at nucleotide 205 of exon 10.
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10
The notes indic ate two mutations at nu cleotide 5380, one that does not change the encoded a mino acid
(silent) and one that does.
F21. While the testimony indicates that the Griffin inventors had discovered a
noteworthy mutation, none of this testimony states that the inventor's recognized that they had
discovered the mutation that caused the condition they were studying.
F22. A page of notes (Exh. 1032) for a lab meeting on 2 December 1993 attributed to
Greengard and Xu discuss the use of the FV1-FV12 primers on eight APC functional sites in the
S family. They report that "[n]ot all of these have been explored in the [S] fa[m]ily as yet." The
notes show that primers FV7/8a correspond to an N-terminal APC cleavage site (Exh. 1032).
F23. The notes report (Exh. 1032) the discovery of five10 nucleotide mutations as
follows:
Nucleotide Effect on protein
2298 Silent
2325 Silent
5380 Silent
5248 (A T) Serine Cysteine
5380 (G A) Valine Methionine
F24. Both of the protein changes caused by mutations are in the phospholipid binding
site, which is probed using primers FV3/4 (Exh. 1032).
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11
The "S1691C (nt A5248T)" mutation is a mutation at nucleotide 5248 (A T) that corresp onds to a change
at amino acid 1691 (S C).
12
Indeed, it is questionable whether there was even a conception. That issue is not before us, but the
identification of a possible cause does not seem to add up to a "a definite and permanent idea of an operative invention,
including every fea ture of the subjec t matter sought to be pate nted". Sewall v. Walters, 21 F.3d 411, 415, 30 USPQ2d
1356, 1358-59 (Fed. Cir. 1994) ; Burroughs Wellcome Co. v. Barr Lab., Inc., 40 F.3d 1223, 1228, 32 USPQ2d 1915, 1919
(Fed. Cir. 1994) ("An idea is de finite and perma nent when the inventor has a spec ific, settled idea, a pa rticular solution to
the problem at hand, not just a general goal or research plan he hopes to pursue.")
F25. The notes (Exh. 1032) do not report a mutation at nucleotide 1691,11 a G A
mutation that changes the encoded amino acid from arginine (R) to glutamine (Q), or a mutation
of any sort in the N-terminal APC cleavage site probed with primers FV7 and FV8.
F26. The notes focus on the nt 5248 (Cys) mutation, indicating that Xu would sequence
the phospholipid binding site where it occurs in other patients that week and that the mutation
does not always show up in LS sequences and may be a "sequencing artifact" (Exh. 1032).
Analysis
If we assume that Dr. Greengard could, and did, read the FV7 sequencing gels of LS and
AS on or before 2 December 1993 and then discussed her finding with Drs. Griffin and
Fernandez, the evidence still does not support a conclusion that Griffin had a reduction to
practice. At best, the evidence Griffin has adduced indicates that the Griffin inventors had, by
2 December 1993, identified a mutation of interest at an interesting place in a gene of interest in
one affected patient.12 Even the inventors' testimony does not attest to the possession of more. It
simply says, as does the corroborating testimony of Fernandez, that they had identified a
mutation. Contemporaneous documentary evidence (Exh. 1032), does not reflect this
identification, but does indicate that the search for the cause was on-going, with other possible
sites to explore and other patients to test.
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13
The test used knowledge of the disease to identify the mutation, which is the mirror image of using the
mutation to identify the disea se. Even assum ing the test could qua lify as a reduction to prac tice, Griffin would still ha ve
to show that the inventors recognized the correlation between that mutation and the disease.
This is not a case that turns on whether the test results are sufficient evidence of a
reduction to practice. Even if we assume that the testing was properly done and properly
interpreted, and if we further accept that the test was equivalent to the diagnostic method of the
count,13 we still have no basis for inferring that the inventors recognized the significance of the
test by 2 December 1993. With hindsight, one can see that the nt 1691 mutation is in a codon
that changes the coding of a critical amino acid (arginine) at a critical place (a terminal cleavage
site), which might have enhanced the significance of the identification, but the testimony of Drs.
Griffin, Greengard, and Fernandez does not even go that far. All they purport to have found was
a point mutation in one patient, while other evidence indicates that they had also
contemporaneously identified several other mutations of interest. We cannot attribute to Griffin,
nunc pro tunc, the knowledge of the significance of the nt 1691 mutation absent support in the
record. The portions of the record to which we have been pointed, including the testimony of the
inventors, does not support a finding that the Griffin inventors had a contemporaneous
understanding of the significance of their discovery.
ORDER
Upon consideration of the arguments and evidence on priority, it is
ORDERED that judgment on priority as to count 4 is awarded against junior party
Griffin;
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14
Note that the examiner has separately determined that claim 80-88 are not patentable although claims 81-88
may be redrafted in independent form to avoid unpatentability (Rule 609(b) statement). This judgment on priority does
not bar the examiner from pursuing this rejection.
FURTHER ORDERED that Griffin is not entitled to a patent containing application
08/410,488 claims 1-4, 7-11, 14, 19-28, 30-32, and 34-40, which correspond to Count 4;
FURTHER ORDERED that, based on the record before us, senior party Bertina is
entitled to a patent containing application 08/454,353 claims 62-88,14 which correspond to
Count 4; and
FURTHER ORDERED that a copy of this decision be given a paper number and be
entered in the administrative records of application 08/410,488 and application 08/454,353.
RICHARD E. SCHAFER
Administrative Patent Judge
JAMESON LEE
Administrative Patent Judge
RICHARD TORCZON
Administrative Patent Judge
BOARD OF PATENT
APPEALS AND
INTERFERENCES
INTERFERENCE
TRIAL SECTION
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15
At Akzo Nobel, N.V., 1330 PICCARD DR STE 206, ROCKVILLE MD 20850-4373, Fax: 301-948-9751.
cc (first-class mail):
Counsel for Griffin
(real party in interest, The Scripps Research Institute):
Talivaldis Cepuritis
OLSON & HIERL, LTD.
20 N WACKER DR FL 36
CHICAGO IL 60606
Fax: 312-580-1189
Counsel for Bertina
(real party in interest, Rijks Universiteit Leiden;
exclusive licensee, Azko Nobel, N.V.):
Ronald J. Kubovcik
Gregory R. Muir15
KUBOVCIK & KUBOVCIK
900 17TH ST NW STE 710
WASHINGTON DC 20006
Fax: 202-887-9093