Ex Parte McAllister et al

Patent Trial and Appeal Board

Nov 9, 2018

14587831 (P.T.A.B. Nov. 9, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/587,831 12/31/2014
26138 7590 11/13/2018
Joseph R. Baker, APC
Gavrilovich, Dodd & Lindsey LLP
4370 La Jolla Village Drive, Suite 303
San Diego, CA 92122
FIRST NAMED INVENTOR
Sean D. McAllister
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
00010-003US3 3013
EXAMINER
MELLER, MICHAEL V
ART UNIT PAPER NUMBER
1655
MAIL DATE DELIVERY MODE
11/13/2018 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SEAN D. MCALLISTER and PIERRE-YVES DESPREZ
Appeal2017-003707
Application 14/587,831
Technology Center 1600
Before TA WEN CHANG, JOHN E. SCHNEIDER, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
Appellants 1 submit this appeal under 35 U.S.C. § 134 involving
claims to a method of treating glioblastoma multiforme with a
therapeutically effective amount of a combination of cannabidiol (CBD) and
tetrahydrocannabinol (THC). The Examiner rejected the claims as
anticipated and obvious2. We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
1 Appellants identify the Real Party in Interest as Sutter West Bay Hospitals.
App. Br. 2.
2 We herein refer to the Specification, filed Dec. 31, 2014 ("Spec."); Final
Office Action, mailed Jun. 22, 2015 ("Final Act."); Appeal Brief, filed Mar.
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Application 14/587,831
STATEMENT OF THE CASE
Appellants' "invention relates to methods and compositions for
treating cancer." Spec. ,r 3. In embodiments, "the cancer is brain cancer,
such as glioblastoma multiforme." Id. ,rs. More specifically, the
Specification describes treating cancer in a subject by administering "a
therapeutically effective amount of a composition comprising a combination
of the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC)."
Id. ,r 8. According to the Specification, "[t]he disclosure demonstrates that
the addition of CBD to 1'19-THC improves the overall potency and efficacy of
1'19-THC in the treatment of cancer ( e.g., glioblastoma multiforme 'GBM')"
and that, in some aspects, this combination "synergistically inhibits GBM
cell growth and induces apoptosis." Id. ,r,r 13-14.
Claims 16-18 are on appeal. 3 Those claims are reproduced below:
16. A method of treating glioblastoma multiforme in a human,
consistent essentially of administering to said human in need of
such treatment a therapeutically effective amount of a
combination compnsmg cannabidiol (CBD) and a
tetrahydrocannabinol (THC).
17. The method of claim 16, wherein the CBD and THC are
in a ratio of 1: 1.
21, 2016 ("App. Br."); Examiner's Answer, mailed Oct. 7, 2016 ("Ans.");
and the Reply Brief, filed Dec. 6, 2016 ("Reply Br.").
3 Claim 19 was rejected under 35 U.S.C. § 112, second paragraph (see Final
Act. (dated June 22, 2015) 16-18), but later canceled in an after-final
amendment. See Interview Summary dated Dec. 22, 2015 ("The amendment
[canceling claim 19] is hereby entered and only claims 16-18 are pending.").
The § 112 rejection of claim 19 is, thus, moot.
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18. The method of claim 16, wherein the treatment of the
glioblastoma multiforme in a human in need thereof is to reduce
cell growth.
App. Br. 27 (Claims App'x).
The claims stand rejected as follows:
I. Claims 16-18 under 35 U.S.C. § I02(b) as anticipated by
Guzman Pastor4 as evidenced by AANS 5 ("Rejection I").
Ans. 2-3.
II. Claims 16-18 under 35 U.S.C. § I03(a) as obvious over
Guzman Pastor as evidenced by AANS ("Rejection II").
Ans. 3--4.
An oral hearing before the Board was held on November 1, 2018, and
a record of the hearing will be provided in the prosecution record.
REJECTION I - ANTICIPATION
Issue
The Examiner finds that "Guzman Pastor teaches that cannabidiol
(CBD) and tetrahydrocannabinol (THC) are both used to treat
glioblastomas," (known as glioblastoma multiforme per AARC). Ans. 2.
The Examiner focuses on Guzman Pastor's claims, finding that "it is made
clear that cannabinoids (plural) are used and in claim 3 it is specified that the
4 Guzman Pastor et al., US 2004/0039048 Al, published Feb. 26, 2004.
5 American Association of Neurological Surgeons, Glioblastoma Multiforme
(April 3, 2015) (.pdf of web pages of record) ("AANS"); see also
https://www.aans.org/Patients/Neurosurgical-Conditions-and-
Treatments/Glioblastoma-Multiforme (last visited Nov. 5, 2018).
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cannabinoids can be CBD and THC." Id. Thus, the Examiner asserts, "it
would have been inevitable that both CBD and THC were used in the same
composition since cannabinoids (plural) are used in the claims." Id. at 2-3.
Appellants argue Guzman Pastor does not describe combination
therapy, much less describe "administering of CBD in combination with
THC" as required in claim 16. App. Br. 5. Appellants argue the Examiner
misinterprets the term "cannabinoids" in Guzman Pastor's claims as
describing a combination of CBD and THC when, in fact, Guzman Pastor
"consistently used 'cannabinoids' (plural) to refer to [administering] only a
single type of cannabinoid." Id. at 7-10 (citing numerous disclosures in
Guzman Pastor). Appellants also contend that claim 3 of Guzman Pastor,
which the Examiner principally relies on, uses Markush-style claim
language to list the cannabinoids: THC (L'i9-tetrahydrocannabinol), L'i8-
tetrahydrocannabinol, cannabinol, and cannabidiol (CBD). Id. at 10;
Guzman Pastor ( claim 3). If anything, Appellants argue, this Markush
language signals a listing of alternative cannabinoids - not combinations of
them. App. Br. 10 (citing MPEP 2173.05(h) ("A 'Markush' claim recites a
list of alternatively useable species .... ") ( emaphasis by Appellants).
Insofar as the Examiner is invoking inherency by asserting that combination
therapy with THC and CBD would have been "inevitable," Appellants argue
the Examiner's position is legally and factually flawed. App. Br. 11-14. 6
6 Appellants' contentions related to a potential interference between the
presently claimed subject matter and claims in U.S. Patent No. 8,632,825 are
not germane to resolution of this appeal. App. Br. 25.
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The issue on appeal is whether a preponderance of the evidence on
this record supports the Examiner's determination that Guzman Pastor (as
evidenced by AANS) describes the subject matter of the appealed claims.
Analysis
To show anticipation, each and every claim element, arranged as in
the claim, must be found in a single prior art reference. Net MoneyIN, Inc. v.
Verisign, Inc., 545 F.3d 1359, 1369--71 (Fed. Cir. 2008) (holding "it is not
enough that the prior art reference ... includes multiple, distinct teachings
that the artisan might somehow combine to achieve the claimed invention.").
We are unpersuaded that Guzman Pastor describes administration of a
therapeutically effective amount of a combination of CBD and THC to treat
glioblastoma multiforme as claimed. Appellants' reading of Guzman Pastor
is more persuasive on this record. The use of plural "cannabinoids" in claim
3 does not require or describe the administration of combinations of the four
natural cannabinoids listed as suggested by the Examiner. When read in
light of Guzman Pastor's entire description - including the copious
citations and text pointed out by Appellants (App. Br. 7-10)-claim 3
suggests picking one of the listed cannabinoids for treatment. The use of the
plural "cannabinoids" does not override the entire description of Guzman
Pastor, none of which expressly describes treatment with combinations of
cannabinoids. The use of Markush-style claim format in claim 3 also
reinforces Appellants' interpretation of Guzman Pastor, reflecting that the
cannabinoids listed are contemplated as alternatives, not combinations.
The Examiner's assertion that combination therapy is "inevitable"
from Guzman Pastor fares no better in establishing that the pending claims
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are anticipated. 7 From a reading of Guzman Pastor, it is not necessarily or
inevitably the case that compositions comprising a combination of CBD and
THC are administered to a subject. To the contrary, as Appellants note,
there are no examples, experiments, or data described where any
combination was administered and no instance where CBD was given even
by itself. App. Br. 11-15. Hence, Appellants contend, Guzman Pastor
"clearly and unequivocally shows that the 'inevitable' did not in-fact
happen." App. Br. 11. "Probabilities or possibilities" do not suffice to show
that a claim limitation is present. In re Oelrich, 666 F .2d 578, 581 (CCP A
1981) ("The mere fact that a certain thing may result from a given set of
circumstances is not sufficient.").
Inasmuch as the Examiner meant to assert that the ordinarily skilled
person would immediately "envisage" treatment with combinations of CBD
and THC because both agents are in a preferred list, we disagree. Ans. 17.
It is true that anticipation may sometimes be found even when specific
subject matter is not explicitly combined in the reference if the person of
ordinary skill in the art would "at once envisage" that subject matter from
the reference's description. See In re Petering, 301 F.2d 676, 681 (CCPA
1962). We are not, however, persuaded that is the case here. We reject the
Examiner's interpretation of the plural "cannabinoids" as indicating
combination therapy for reasons discussed above. Also, this is not a case
7 For claim 17, the Examiner asserts that "[i]t is also inevitable that a ratio of
1: 1 was used with respect to both CBD and THC since they were both noted
to have equal importance in the claims [of Guzman Pastor]." Ans. 3. As
Appellants point out, the Examiner provides no legal or scientific basis for
this assertion. App. Br. 9-10.
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where combination therapy using certain active agents is expressly set out in
a working example, with a short list of substitute active agents also listed -
a fact pattern more in line with the notion that a skilled artisan would at once
envisage a substitute agent being used in place of an exemplified agent.
Here, as already explained, there is simply no therapy using combinations of
natural cannabinoids described whatsoever in Guzman Pastor. That change
to Guzman Pastor, to the extent it could or would be made, raises the issue
of obviousness, not anticipation. 8
Conclusion
For the above reasons, we conclude that the preponderance of the
evidence on this record does not support the Examiner's finding that
Guzman Pastor anticipates claims 16 ( or dependent claims 17 and 18).
REJECTION II- OBVIOUSNESS
Issue
The Examiner alternatively concludes that claims 16-18 would have
been obvious over Guzman Pastor. Ans. 3--4. According to the Examiner:
In the event it is seen that it would not have been inevitable that
both CBD and THC were used at the same time in the same
composition ... then it would have been obvious for one having
8 Appellants also contend the ordinarily skilled person would not have
"envisaged" therapy with CBD in combination with THC because CBD was
(contrary to Guzman Pastor's suggestion) a known antagonist of the CB 1 and
CB2 receptors that Guzman Pastor was seeking to agonize with THC and
synthetic agents. App. Br. 15-17; see, e.g., Guzman Pastor ,r,r 20, 34, 36;
McAllister Deel. (dated Sept. 21, 2015) ,r,r 4--7 ("CBD and THC work in
conflict (really, opposite to each other) on CBI and CB2 receptors"). We
address this evidence below related to the rejection for obviousness.
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ordinary skill in the art at the time the invention was made to use
both CBD and THC at the same time to treat glioblastomas since
the claims clearly state that both CBD and THC can be used to
treat glioblastomas.
Id. at 4; see also Final Act. 14--15 ("It would have been obvious to one of
ordinary skill in the art ... to combine the components for their known
benefit since each is well known in the art for the same purpose") ( citing
KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398 (2007) and In re Kerkhoven,
626 F.2d 846,850 (CCPA 1980)).
Although we agree with Appellants that Guzman Pastor does not
expressly or inherently describe combination therapy with THC and CBD,
that is not dispositive for the obviousness inquiry. Guzman Pastor teaches or
suggests that cannabinoids including either THC or CBD can be used to treat
glioblastomas. See, e.g., Guzman Pastor, ,r,r 2, 20, claims 1-3. This is true
regarding Guzman Pastor's disclosure even under the interpretation
advanced by Appellants - where "cannabinoids" should be interpreted as
requiring a selection of one of the cannabinoid agents in Guzman Pastor's
claim 3, for example, which lists both THC and CBD. App. Br. 7-11.
Given that Guzman Pastor suggests that compositions including either
THC or CBD may provide treatment for glioblastomas, it follows from logic
and the law that it is generally obvious to combine such compositions to
form a third composition used for the same purpose. In re Kerkhoven, 626
F.2d 846, 850 (CCPA 1980) ("It is prima facie obvious to combine two
compositions each of which is taught by the prior art to be useful for the
same purpose, in order to form a third composition which is to be used for
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the very same purpose .... [T]he idea of combining them flows logically
from their having been individually taught in the prior art.").
But that analysis also does not end the inquiry, because Appellants
have provided further evidence that directly bears on the issues of a skilled
person's motivation for giving combination therapy and the reasonable
expectation of success with such therapy. In order to sustain the § 103
rejection, the preponderance of the evidence must demonstrate that the
ordinarily skilled person would have been motivated to administer
combinations of CBD and THC to subjects with a reasonable expectation of
success in treating glioblastoma. On these issues, and notwithstanding
Guzman Pastor's disclosure, the evidence on this record tilts in Appellants'
favor.
As discussed above, Guzman Pastor describes no examples,
experiments, or data to back up its suggestion that CBD is capable of
treating glioblastoma. That suggestion is provided in Guzman Pastor's
claims. Guzman Pastor, claims 2-3. The only other mention of CBD
("cannabidiol") is in paragraph 20, where it states that the invention is
applicable to CBD and suggests that CBD will behave like other natural
cannabinoids (i.e., THC)- as an agonist of the CB1 and CB2 receptors.
Guzman Pastor ,r 20.
Evidence submitted by Appellants, however, demonstrates that this
may be scientifically inaccurate in that CBD is not a CB 1 and CB2 agonist.
App. Br. 20-21. Rather, it was apparently well known prior to the invention
that CBD was a potent antagonist to CB1 and CB2 activation. McAllister
Deel. ,r,r 4--7 ("CBD does not efficiently interact nor activate CBI and CB2
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receptors, and therefore would antagonize the effects of drugs activating
CBI and CB2 receptors."); Schowalter9 (showing that CBD's affinity for
CB 1 and CB2 receptors is approximately 100-fold lower than those
receptors affinity for THC). Indeed, in a study by Thomas, 10 the researchers
found that cannabidiol (CBD) displays unexpectedly high potency as an
antagonist of CB1 and CB2 receptor agonists. So, as one of the inventors
testifies:
[O]ne of ordinary skill in the art in 2007 would not have used
CBD in combination with THC as alleged by the Office, as the
two compounds were recognized as having opposite effects on
the antiproliferative effects of CB 1 and CB2 receptors identified
as being important for the methods of Guzman Pastor.
McAllister Deel. ,r 7. When other CB 1 and CB2 antagonists were
administered in Guzman Pastor "an effective prevention was observed of the
cell death induced by THC (FIG. 5a)." Guzman Pastor ,r 16; see also id.
,r 36 (describing THC's antiproliferative and cell-death inducing effect,
which effect was prevented upon the addition of CB1 and CB2 antagonists);
Reply Br. 8. Put differently, because killing the cancer cells with THC is
desired in Guzman Pastor, this antagonist activity is the opposite of the
effect desired. Appellants therefore argue that "one of skill in the art,
9 Vincent M. Schowalter et al., Evaluation of Binding in a Transfected Cell
Line Expressing a Peripheral Cannabinoid Receptor (CB2): Identification of
Cannabinoid Receptor Subtype Selective Ligands, 278:3 THE JOURNAL OF
PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 989--96 (1996).
10 A Thomas et al., Cannabidiol displays unexpectedly high potency as an
antagonist of CB1 and CB2 receptor agonists in vitro, 150 BRITISH JOURNAL
OF PHARMACOLOGY 613-23 (2007).
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knowing that CBD is an antagonist and reading the fact that Guzman Pastor
et al. teach antagonists inhibit cancer cell death caused by THC would not
have combined CBD with THC as posed by the Examiner." Id. (bold font
deleted). When balanced against Guzman Pastor's unsubstantiated
suggestion that CBD is a CB 1 and CB2 receptor agonist for treating
glioblastoma, Appellants' argument and cited evidence is more persuasive. 11
And, on this record, the Examiner has not established a sufficient evidentiary
basis to support the finding that the ordinarily skilled person would have
been motivated to administer combination therapy with both CBD and THC
with a reasonable expectation of success.
Because we find the evidence on the issues of motivation to modify
the prior art and the reasonable expectation of success insufficient to support
a prima facie conclusion of obviousness, we decline to reach Appellants'
evidence of alleged unexpected synergy with the claimed combination
therapy.
Conclusion of Law
The preponderance of the evidence on this record fails to support the
Examiner's conclusion that claims 16-18 would have been obvious over
Guzman Pastor (as evidenced by AANS).
11 The Examiner never squarely rebuts this evidence beyond reiterating
Guzman Pastor's teachings. Ans. 36-38 ("That teaching [in Guzman Pastor]
is not negated because of what others may teach about the activities of the
two cannabinoids in a different context"). But, as noted, the lack of
supporting detail in Guzman Pastor is outweighed by the testimony and
multiple publications in the scientific literature cited by Appellants.
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SUMMARY
We reverse the rejections for anticipation and obviousness on appeal.
REVERSED
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