Ex Parte Farries et al

Patent Trial and Appeal Board

Aug 30, 2016

13392570 (P.T.A.B. Aug. 30, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/392,570 03/12/2012 Timothy Parries
22925 7590 09/01/2016
PHARMACEUTICAL PATENT ATTORNEYS, LLC
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ATTORNEY DOCKET NO. CONFIRMATION NO.
Ark- GB0916997 1063
EXAMINER
HAMMELL, NEIL P
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
09/01/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
docket@LicensingLaw.net
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TIMOTHY F ARRIES and DAVID ECKLAND 1
Appeal2015-001484
Application 13/392,570
Technology Center 1600
Before JEFFREY N. FREDMAN, RYAN H. FLAX, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims 19-46 to
gene therapies for cancer, which have been rejected as anticipated, obvious
and nonenabled. We have jurisdiction under 35 U.S.C. § 6(b ).
We reverse.
STATEMENT OF THE CASE
Background
"Malignant glioma is a cancerous tumour that is confined to the brain
and only rarely spreads further." (Spec. 1: 10-11 ). "The current standard
1 Appellants identify the Real Party in Interest as Fin Vector Vision
Therapies Ltd. (App. Br. iv).
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Application 13/392,570
therapy involves surgically removing the solid tumour mass and initiating
radiotherapy and/or chemotherapy." (Id. at 1:11-13). "Currently most
available cancer medicines are generally very toxic and many do not readily
reach the brain tumour." (Id. at 1:15-16). "The present invention is based
on a study, which shows that locally administered antigens in combination
with a pre-existing immunoresponsiveness to those antigens, enhances the
efficacy of an adenoviral-based gene therapy treatment for glioma." (Id. at
2:28-31).
The Issues
A. Claims 19-24 are rejected under 35 U.S.C. § 102(b) as being
anticipated by Yla-Herttuala. 2
B. Claim 25 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Yla-Herttuala and Ulasov. 3
C. Claims 33-38 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Yla-Herttuala and King. 4
D. Claim 39 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Yla-Herttuala, King, and Ulasov.
2 U.S. Pat. No. 6,579,855 Bl, issued June 17, 2003.
3 IV Ulasov et al., Combination of adenoviral virotherapy and temozolomide
chemotherapy eradicates malignant glioma through autophagic and
apoptotic cell death in vivo, 100 BRITISH JOURNAL OF CANCER 1154--1164
(2009).
4 Gwendalyn D. King et al., High-Capacity Adenovirus Vector-Mediated
Anti-Glioma Gene Therapy in the Presence of Systemic Antiadenovirus
Immunity, 82 JOURNAL OF VIROLOGY 4680-4684 (2008).
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E. Claims 19--39 are rejected under 35 U.S.C. § 112, first paragraph, as
nonenabled.
Anticipation
ISSUE
Does the preponderance of evidence of record support the Examiner's
finding that Yla-Herttuala discloses the invention of claims 19--24?
FACTUAL FINDINGS (FF)
FF 1. The Specification teaches that
In a preferred embodiment, stimulation of the immune system
is used to increase the immunoresponsiveness of the patient that
is to be administered vector antigens to enhance the therapeutic
efficacy of the gene therapy adenoviral vector. This
immunostimulation may be achieved by either nonspecific
activation of immune reactions or by stimulation specifically
relating to the therapy by the immunogens (or antigens) of the
gene therapy vector, or the tumour.
(Spec. 4:3-9).
FF 2. Yla-Herttuala teaches that patients "underwent craniotomy and
tumour resection" after which the "diagnosis of malignant glioma
was confirmed .... " (Yla-Herttuala 3:17-30).
FF 3 Yla-Herttuala teaches that "[a]fter tumour resection, HSVtk
retrovirus packaging cells were injected into the wall of the tumour
cavity" of patients. (Id. at 3:30-34).
FF 4 Yla-Herttuala teaches that "[a]nti-virus antibodies were measured
before and two weeks after the gene transfer." (Id. at 4:9--10).
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FF 5 Yla-Herttuala teaches an increase in adenovirus antibodies in 3 of 7
Adv/tk-treated patients. (Id. at 5:48-50). These patients had a
measurable antivirus titer as opposed to the remaining four, who had
no measurable titer. (Id. at Table 1 ). Based on these data, we find
that not all the patients studied in Yla-Herttuala had measurable
baseline antiviral immunity prior to administration of the viral vector;
therefore, confirmation of measurable level of immunity was not
required to proceed to viral vector administration.
ANALYSIS
Appellants' independent claim 19 is reproduced below:
19. In a method of treating cancer in a human by partial or
complete resection of tumor from said human, the
improvement comprising:
a. Determining the level of immunity against a viral
vector,
b. Confirming said human has a measurable level of
immunity against said vector, and
c. Administering to said human said viral vector.
The Examiner finds that Yla-Herttuala teaches "resecting malignant
gliomas from human patients," "determining and confirming a measurable
level of immunity against a viral vector," and "administering the viral vector
to the patients." (Ans. 2). As Yla-Herttuala performs the step of measuring
antibodies both before and after administration of the viral vector, rather
than exclusively before administration (FF 3--4), the Examiner's rejection
requires that the steps of claim 19 be performed out of the order they are
written:
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Applicants acknowledge that Yla-Herttuala determined and
confirmed a measurable level of immunity in 3 out of the 7
Adv/tk-treated patients []. Therefore, it is clear that Yla-
Herttuala determined and confirmed a measurable level of
immunity against the vector. As discussed above, the claims do
not require that this determination and confirmation occurs
before the administration of the viral vector.
(Final Act. 15).
Appellants argue that Yla-Herrtuala cannot anticipate because the
steps of claim 19 are limited to the "specific order there specified" by the
prosecution history, the physical nature of the steps, and the literal claim
language. (App. Br. 4--5). We find that the broadest reasonable
interpretation of claim 19 requires that continuing the method to step "c,"
that is, administering the viral vector, first requires confirmation at step "b"
that the patient has a measurable level of immunity against the vector;
otherwise the method does not continue to step "c." See In re Am. A cad. of
Science Tech Center, 367 F.3d 1359, 1364 (Fed. Cir. 2004) ("The Patent and
Trademark Office ('PTO') determines the scope of claims in patent
applications not solely on the basis of the claim language, but upon giving
claims their broadest reasonable construction 'in light of the specification as
it would be interpreted by one of ordinary skill in the art."').
While Yla-Herttula does disclose measuring antibodies before and after
injecting HSVtk retrovirus, it is not disputed that Yla-Herttuala does not
disclose that one must first confirm measurable immunity before then
administering an injection. (see, e.g., Final Act. 17). Because the process
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disclosed by Yla-Herttuala does not so restrict its viral vector administration
step, it does not disclose the claimed method.
We are persuaded by Appellants' argument that the language of claim
19 mandates that the steps be implemented in the sequence as written. (App.
Br. 7). In particular, we find the claim terms "said human" and "said
vector/said viral vector" would lack antecedent basis if not read in the order
claim 19 is written. In addition, this interpretation is consistent with the
Specification, which states that "stimulation of the immune system is used to
increase the immunoresponsiveness of the patent that is to be administered
vector antigens to enhance the therapeutic efficacy of the gene therapy
adenoviral vector." (FF 1, emphasis added). In order for vector antigens to
be administered after immunoresponsiveness is increased, claim 19 must be
performed in the order as written.
Accordingly, we find Yla-Herttuala does not anticipate claim 19
because Yla-Herttuala does not perform the steps of the claimed method in
the same way as recited in claim 19. See Net MoneyIN, Inc. v. VeriSign,
Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008). ("[U]nless a [prior art] reference
discloses within the four comers of the document not only all of the
limitations claimed but also all of the limitations arranged or combined in
the same way as recited in the claim, it cannot be said to prove prior
invention of the thing claimed and, thus, cannot anticipate under 35 U.S.C.
§ 102. ") We do not find it necessary to reach Appellants' other arguments
on this issue. 5
5 Although we do not reach Appellants' other arguments, we note multiple
occasions where Appellants' counsel disparages the Examiner (See, e.g., Reply
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Obviousness
ISSUE
Does the preponderance of evidence on this record support the
Examiner's finding that Yla-Herttula and Ulasov render obvious the
invention of claim 25?
ANALYSIS
Based on the combination of Yla-Herttuala and Ulasov, the Examiner
concludes that, at the time Appellants' invention was made, it would have
been obvious to "have modified the method of Yla-Herttuala by further
administering temozolaminde ... for the advantage of treating the glioma."
(Ans. 3). The Examiner, however, has not established that Ulasov makes up
Br. 3, 7). We remind Appellants of the requirement to conduct all business
with the Office with decorum and courtesy.
Applicants and their attorneys or agents are required to conduct
their business with the United States Patent and Trademark
Office with decorum and courtesy. Papers presented in
violation of this requirement will be submitted to the Director
and will not be entered. A notice of the non-entry of the paper
will be provided. Complaints against examiners and other
employees must be made in correspondence separate from other
papers.
37 C.F.R. § 1.3 ("Business to be conducted with decorum and courtesy").
We find comments such as those do not represent Appellants' best interests,
arguably violate at least the spirit of Rule 1.3, and are not helpful in aiding the
Board to properly resolve the issues necessary to render a decision on the merits.
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for the deficiency of Yla-Herttuala, as discussed above. Accordingly, we
find the preponderance of evidence on this record does not support the
Examiner's finding on this issue.
ISSUE
Does the preponderance of evidence on this record support the
Examiner's finding that Yla-Herttula and King render obvious the invention
of claims 33-38?
FACTUAL FINDINGS (FF)
FF 6 King teaches that rats were "systemically immunized [] with a first-
generation Ad[ enovirus ]" or control saline, then "rat glioma cell line
CNS-I" was implanted into their striata. (King 4681 i-f 2). "One week
later, groups of animals received an intratumoral injection of Ad-
TKL, HC-Ad-TK, Ad-B-galactosidase [], HC-Ad- Bgal, or saline."
(Id.)
FF 7 King discloses that "only treatment with HC-Ad-TK significantly
extended the survival of preimmunized rats." (Id.)
ANALYSIS
Appellants' independent claim 33 is reproduced below:
33. A method comprising:
a. diagnosing cancer in a human, and then
b. in any sequence:
- performing a partial or complete resection of
tumor from said human, and
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- determining the level of immunity against a viral
vector, and confirming said human has a
measurable level of immunity against said
vector; and then
c. Administering to said human said viral vector.
Based on the combination of Yla-Herttula and King, the Examiner
concludes that, at the time Appellants' invention was made, it would have
been obvious to
have modified the method of Yla-Herttuala by determining and
confirming whether a patient had a measurable level of
immunity against a viral vector prior to administering to the
human the viral vector ... because this would have been
important to inform whether one should administer a first-
generation adenoviral vector or a second-generation high-
capacity adenoviral vector. 6
(Ans. 5).
The Examiner further states "[t]he claims broadly recite 'viral vector'
and therefore encompass any viral vector including first-generation and
second-generation adenoviral vectors." (Ans. 16). According to the
Examiner
The rejection argues that in the event that one determined and
confirmed a measurable level of immunity to a viral vector in a
human, one would have chosen to administer the second-
6 The Examiner's reference to a "second-generation high capacity adenoviral
vector" refers to HC-Ad-TK, which is an adenovirus but is not the same
adenovirus that was first injected into the rats in King. (King 4681 i-f 2). It
is therefore a second-generation adenovirus with respect to the injected
adenovirus.
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(Id.).
generation HC-Ad-TK viral vector as taught by King because
this would have been more likely to be able to effectively treat
the glioblastoma.
The Examiner finds
King teaches that T-cells recognize the expression of viral
epitopes from first-generation adenoviral vectors in infected
cells leading to T-cell immunity ... and further that the
presence of preexisting immune responses against first-
generation adenoviral vectors hampers therapeutic transgene
expression resulting in diminished clinical efficacy of the
treatment .... In contrast, even in the presence of a pre-existing
immune response, since second-generation adenoviral vectors
do not express viral antigenic epitopes in infected cells, anti-
adenovirus immune T cells do not have any adenovirus-derived
epitopes that they can recognize on infected cells, and thus
transgene expression from such vectors remains stable in
infected cells.
(Ans. 17, emphasis added).
The Examiner further finds "King concludes that the administration of
second-generation adenoviral vectors represents a powerful treatment for
glioblastomas even in patients who have a preexisting immune response to
the adenovirus." (Id.)
Appellants argue King "expressly teaches away from using Yla-
Herttuala's viral vector in immune incompetent patients." (App. Br. 8).
We find the Examiner has not established a prima facie case of
obviousness on these references. We have discussed the deficiency of Yla-
Herttuala above and find that King does not address that deficiency.
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King teaches success through administration of a first-generation viral
vector and treatment using a second-generation viral vector. King teaches
away from use of a first-generation viral vector as the "said viral vector" to
be administered in the last step of claim 33. Rather, King teaches the second
generation vector is a "powerful treatment for glioblastomas" and "only
treatment with HC-Ad-TK significantly extended the survival of
preimmunized rats." (Ans. 1 7; King 4 6 81 i1 2).
We find the second generation vector of King cannot be used to
perform the method of claim 33 because the recited step of "confirming said
human has a measurable level of immunity against said vector" requires that
the vector express a viral antigenic epitope, against which the detected
immune response is mounted. This "said vector" is the same vector that is
later administered to the patient in the final step "[a ]dministering to said
human said viral vector." As discussed above regarding construction of the
claims at issue, we find the "said viral vector" in the final step of claim 33
must be identical to the first referenced viral vector for the claim to make
sense.
Nor can the second generation vector disclosed by King be used in the
claimed method because it does not express a viral antigenic epitope against
which an immune response can be generated and later measured. (Ans. 17).
Accordingly, we find King does not remedy the deficiencies of Yla-
Herttuala.
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ISSUE
Does the preponderance of evidence on this record support the
Examiner's finding that Yla-Herttula, King, and Ulasov render obvious the
invention of claim 39?
ANALYSIS
Based on the combination of Yla-Herttuala, King, and Ulasov, the
Examiner concludes that, at the time Appellants' invention was made, it
would have been obvious to "have modified the method of Yla-Herttuala by
further administering temozolaminde ... for the advantage of treating the
glioma." (Ans. 6). The Examiner has not established that Ulasov remedies
the deficiencies in Yla-Herttuala and King for the reasons discussed above.
Enablement
ISSUE
Does the preponderance of evidence on this record support the
Examiner's finding that claims 19-46 are not enabled?
FACTUAL FINDINGS
FF 8 The Specification discloses
According to a second aspect, the present invention is a product
comprising an immunostimulant and a vector comprising a
transgene that promotes death of neoplastic cells, for
simultaneous, sequential or separate administration in the
treatment of cancer.
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According to a third aspect, the present invention is a method of
selecting patients for treatment with a product as defined above,
comprising determining ex vivo the level of immunity against
the vector, in a sample taken from a patient, and selecting the
patient for treatment if the level of immunity is above a
predetermined level.
(Spec. 3:1-14).
ANALYSIS
The Examiner rejected claims 19-25 and 33-39
because the specification, ... does not reasonably provide
enablement for determining the level of immunity against a
viral vector that does not comprise a transgene or comprises any
transgene and any route of administration of the viral vector.
The specification does not enable any person skilled in the art
to which it pertains, or with which it is most nearly connected,
to practice the invention commensurate in scope with these
claims.
(Ans. 7).
The Examiner finds the Specification "teaches a single example" in
which "the viral vector is injected to the brain tumor cavity resulting from
the tumor resection." (Id.) The Examiner cites a literature review in support
of the Examiner's concern regarding the safety and efficacy of the claimed
method (id. at 8-9) and finds that "the specification does not provide a
single working example of a human who had an immune response to a viral
vector 'induced' and then the administration of the viral vector treated
cancer as recited in the preamble." (Id. at 17-18). The Examiner further
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finds the claims are "sufficiently broad that they encompass treating cancer
by administering just any viral vector." (Id. at 9).
Appellants argue the Specification provides an enabling disclosure
and that the Examiner "provides no evidence to doubt the objective truth of
the inventors' disclosure." (App. Br. 9). Appellants cite to evidence in the
record provided by the Examiner that teaches "a viral vector that does not
comprise a transgene" and a method for "determining the level of immunity
against a viral vector." (Id. at 10). Appellants argue that because
"determining immunity against viral vector given by 'any route of
administration' is known," their Specification need not teach it. (Id. at 11 ).
While we share the Examiner's concern that methods of treating
patients must be made safe, the scope of our review on this issue concerns
only whether Appellants have enabled the claimed methods. Considerations
about safety are entertained by the Food and Drug Administration (FDA),
not the Patent and Trademark Office. See In re Brana, 51F.3d1560, 1567
(Fed. Cir. 1995).
We are not persuaded by the Examiner's concern that one of skill in
the art could not measure immunity relative to the vector. The Specification
describes a method of inducing an immune response using a viral vector
(FF 1, FF 8) and data reflecting success in measuring the immune response.
(Spec, Tables 1-2). Subsequent steps of the claimed methods either
represent techniques known to one of ordinary skill in the art, such as
"[a]dministering to said human said viral vector" or adding a medication
such as temozolamide, or narrow the claims by specifying the type of vector
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(e.g., transgene), type of cancer (e.g., glioma) or further describe a method
step (e.g., administering to the cavity created by resection of said tumor).
We do not find the teachings of King helpful on the issue of the scope
of enablement as that reference focused on success obtained using a second
generation vector to which there was no detected immunity due to a lack of
expressed epitopes, as discussed above.
With regard to general scope of the claims, we find the invention is
constrained by the claim language and the Specification in that an immune
response must be detected in the subject prior to administration of the viral
vector, as discussed above. Therefore, we find the claims are adequately
enabled within the provided scope. See AK Steel Corp. v. Sollac, 344 F.3d
1234, 1244 (Fed. Cir. 2003) (citation omitted). ("[A]s part of the quid pro
quo of the patent bargain, the applicant's specification must enable one of
ordinary skill in the art to practice the full scope of the claimed invention.
That is not to say that the specification itself must necessarily describe how
to make and use every possible variant of the claimed invention, for the
artisan's knowledge of the prior art and routine experimentation can often
fill gaps, interpolate between embodiments, and perhaps even extrapolate
beyond the disclosed embodiments, depending upon the predictability of the
art.")
In any event, "[i]t is well settled that patent applicants are not required
to disclose every species encompassed by their claims, even in an
unpredictable art." In re Angstadt, 537 F.2d 498, 502---03 (CCPA 1976).
Although the disclosure must provide enablement commensurate with the
scope of the claims, "[t ]he enablement requirement is met if the description
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enables any mode of making and using the invention." Johns Hopkins Univ.
v. Cellpro Inc., 152 F.3d 1342, 1361 (Fed. Cir. 1998) (quoting Engel Indus.,
Inc. v. Locliformer Co., 946 F.2d 1528, 1533 (Fed. Cir. 1991)).
We find Appellants have sufficiently described a method of making and
using the invention and that one of skill in the art could, guided by the
Specification, apply ordinary skill to practice the claimed invention without
undue experimentation. Accordingly, the preponderance of evidence does
not support the Examiner's rejection on this issue.
Conclusion of Law
The preponderance of the evidence relied upon by the Examiner fails
to support a finding of anticipation, obviousness or lack of enablement.
SUMMARY
The rejection of claims 19--24 under 35 U.S.C. § 102(b) as being
anticipated by Yla-Herttuala is reversed.
The rejection of claim 25 under 35 U.S.C. § 103(a) as unpatentable
over Yla-Herttuala and Ulasov is reversed.
The rejection of claims 33-38 under 35 U.S.C. § 103(a) as
unpatentable over Yla-Herttuala and King is reversed.
The rejection of claim 39 under 35 U.S.C. § 103(a) as unpatentable
over Yla-Herttuala, King, and Ulasov is reversed.
The rejection of claims 19--39 under 35 U.S.C. § 112, first paragraph,
as nonenabled is reversed.
REVERSED
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