MERCK & CIE

Patent Trials and Appeals Board

Mar 19, 2021

2020004905 (P.T.A.B. Mar. 19, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
16/212,056 12/06/2018 Rudolf MOSER MERCK-4424-C01 1228
23599 7590 03/19/2021
MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BLVD.
SUITE 1400
ARLINGTON, VA 22201
EXAMINER
KIFLE, BRUCK
ART UNIT PAPER NUMBER
1624
NOTIFICATION DATE DELIVERY MODE
03/19/2021 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):
docketing@mwzb.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte RUDOLF MOSER, VIOLA GROEHN, THOMAS EGGER,
and THOMAS AMMANN1
____________

Appeal 2020-004905
Application 16/212,056
Technology Center 1600
____________

Before FRANCISCO C. PRATS, JEFFREY N. FREDMAN, and
JOHN G. NEW, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies Merck & Cie as the real party-in-
interest. App. Br. 1.

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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 18, 24, and 26 as unpatentable under
35 U.S.C. § 112(a) as lacking written descriptive support.
Claim 18 also stands rejected as unpatentable under 35 U.S.C.
§ 112(a) as lacking enablement.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to the hemisulfate salt of
5,10-methylene-(6R)-tetrahydrofolic acid, preferably in substantially
crystalline form, as well as pharmaceutical compositions and uses thereof in
therapy, preferably chemotherapy. Abstr.

REPRESENTATIVE CLAIM
Claim 18 is representative of the claims on appeal and recites:
18. A method for lowering the risk of cancer, comprising
administering an effective amount of a hemisulfate salt of 5,10-
methylene-(6R)-tetrahydrofolic acid or a solution prepared from
said hemisulfate salt or a lyophilisate prepared from said
hemisulfate salt or a reconstituted solution of said lyophilisate to
a subject in need thereof.

App. Br. 7.

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ISSUES AND ANALYSIS
We agree with, and expressly adopt, the Examiner’s findings,
reasoning, and conclusion that claims 24 and 26 lack written descriptive
support and that claim 18 is not enabled by Appellant’s Specification. We
reverse the Examiner’s conclusion that claim 18 lacks written descriptive
support. We address below the arguments raised by Appellant.

A. Rejection of claims 18, 24, and 25 for lack of written description

Issue 1: claim 18
Appellant argues that the Examiner erred in concluding that the
limitation of claim 18 reciting “lowering the risk of cancer” is new matter.
App. Br. 2.

Analysis
The Examiner finds that claims 18, 24, and 26 each contain subject
matter that was not described in Appellant’s Specification in such a way as
to reasonably convey to one skilled in the relevant art that the inventor had
possession of the claimed invention at the time the application was filed.
Final Act. 2. Specifically, the Examiner concludes that the preamble of
claim 18 reciting a “method for lowering the risk of cancer” was not
previously disclosed or present in the Specification, and is therefore is new
matter. Id.
Appellant argues that the Examiner has failed to establish a prima
facie case supporting the written description rejection of claim 18, because
the Examiner failed to provide any evidence or rationale beyond a bare lack
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of literal support allegation in support of such a rejection. App. Br. 2.
Appellant points to the Specification’s disclosure that “[l]ikewise the term
‘treatment’ as used herein refers to (i) prevention of the disease; and/or (ii)
inhibition of the disease (e.g.[,] arresting further development of the
pathology and/or symptomatology); and/or (iii) amelioration of the disease
(e.g.[,] reversing the pathology and/or symptomatology).” Id. (quoting Spec.
13). Appellant further contends that the Specification discloses that “[i]n a
further aspect, the present invention is directed to the use of a hemisulfate
salt of (6R)-5,10-CH2-THF (or pharmaceutical compositions thereof) in
therapy, preferably in cancer chemotherapy.” Id. at 2–3 (quoting Spec. 4).
Appellant argues that the Specification thus describes the use of the
compound recited in the claims for use in therapy and lists cancer
chemotherapy as a preferred embodiment. App Br. 3. According to
Appellant, a person of ordinary skill in the art would have clearly understood
therapy as being inclusive of lowering the risk of disease, and especially in
view of the definition of therapy provided in the disclosure. Id. Appellant
argues further that a skilled artisan would have understood that “treatment,”
as disclosed by the Specification, would include prevention, inhibition, and
amelioration of the disease. Id.
Appellant asserts that the term “prevention” in this art would have
been understood to mean that the risk of cancer would be decreased; i.e., that
prevention is supportive of the claimed “lowering the risk of disease.” App.
Br. 3. Appellant argues that cancer prevention is inclusive of a variety of
things one can do, e.g., avoiding the use of tobacco, using sunblock, etc. Id.
Appellant asserts that these preventive measures would have been
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understood by a person of ordinary skill in this particular art to be measures
taken to reduce the risk of cancer. Id.
Similarly, argues Appellant, the additional terms cited, such as
“inhibition,” would also have conveyed “lowering the risk of cancer” to
those of ordinary skill in the art. Id. Similarly, Appellant contends, the term
“amelioration” is inclusive of reversing the pathology and/or
symptomatology, and therefore inclusive of lowering the risk of the
pathology and/or symptomology. Id.
The Examiner acknowledges that behaviors such as avoiding tobacco,
or using sunblock, are known to reduce the risk of certain cancers. Ans. 4.
The Examiner finds, however, that Appellant’s Specification does not
support administering a hemisulfate salt of 5,10-methylene(6R)-
tetrahydrofolic acid to lower the risk of cancer. Id.
We are not persuaded by the Examiner’s reasoning. Claim 18 recites,
in relevant part: “A method for lowering the risk of cancer, comprising….”
Appellant’s Specification does not define the term “lowering the risk of
cancer,” and so we employ the broadest reasonable interpretation of the term
consistent with Appellant’s Specification, and as it would be interpreted by
one of ordinary skill in the art. See Phillips v. AWH Corp., 415 F.3d 1303,
1316 (Fed. Cir. 2005). Consequently, we do not construe this broad
language to mean only “lowering the risk of developing cancer,” but rather
interpret it to mean lowering any risk associated with cancer, including
developing cancer and, additionally, those risks associated with having
cancer, including mortality.
The written description requirement of Section 112(a) requires that
the Specification must “clearly allow persons of ordinary skill in the art to
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recognize that [the inventor] invented what is claimed.” Ariad Pharms., Inc.
v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (alteration in
original) (quoting Vas–Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed.
Cir. 1991)). The test for the sufficiency of the description is “whether the
disclosure of the application relied upon reasonably conveys to those skilled
in the art that the inventor had possession of the claimed subject matter as of
the filing date.” Id. Specifically, the Specification “must describe an
invention understandable to that skilled artisan and show that the inventor
actually invented the invention claimed.” Id.
Appellant’s Specification discloses that “in a further aspect, the
present invention is directed to the use of a hemisulfate salt of (6R)-5,10-
CH2-THF (or pharmaceutical compositions thereof) in therapy, preferably in
cancer chemotherapy.” Spec. 4. The Specification further discloses that:
The term “therapeutically effective amount” refers to the amount
of active compound that elicits the biological or medicinal
response in a tissue, system, animal, individual or human that is
being sought by a skilled practitioner (e.g.[,] researcher,
veterinarian, medical doctor or other clinician or caregiver),
which includes (i) prevention of the disease; and/or (ii) inhibition
of the disease (e.g.[,] arresting further development of the
pathology and/or symptomatology); and/or (iii) amelioration of
the disease (e.g.[,] reversing the pathology and/or
symptomatology). Likewise the term “treatment” as used herein
refers to (i) prevention of the disease; and/or (ii) inhibition of the
disease (e.g. arresting further development of the pathology
and/or symptomatology); and/or (iii) amelioration of the disease
(e.g.[,] reversing the pathology and/or symptomatology).

Spec. 13. Appellant’s Specification thus teaches not only prevention of
cancer, but also inhibition and/or amelioration of cancer, both with respect to
the disease’s pathology and/or symptoms. We agree with Appellant that the
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Specification thus provides sufficient written descriptive support of the term
“lowering the risk of cancer” because it discloses that administering an
effective dose of the claimed composition: (1) prevents development of
cancer; and (2) inhibits or ameliorates the progress of the pathology and/or
symptoms of the disease. We consequently reverse the Examiner’s rejection
of claim 18.

Issue 2: claims 24 and 26
Appellant argues that the Examiner erred in concluding that the
Specification fails to provide adequate written descriptive support for the
limitations reciting: “A method of treating … osteosarcoma,” because it is
new matter. App. Br. 3.

Analysis
Appellant points to the Specification’s disclosure that “[i]n a further
aspect, the present invention is directed to the use of a hemisulfate salt of
(6R)-5,10-CH2-THF (or pharmaceutical compositions thereof) in therapy,
preferably in cancer chemotherapy.” App. Br. 4 (quoting Spec. 4).
Appellant asserts that the Specification thus describes the use of the
composition for use in therapy and lists cancer chemotherapy as a preferred
embodiment. Id. According to Appellant, a person of ordinary skill in the
art would understand “cancer therapy” as including therapy for
osteosarcoma, and that Appellant was in possession of the claimed invention
at the time of filing. Id.
Appellant argues further that the Specification discloses methotrexate,
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doxorubicin, and cisplatin as drugs that are suitable for combination therapy
with the claimed composition. App. Br. 4 (citing Spec. 11). According to
Appellant, these drugs are three primary drugs approved for osteosarcoma
therapy, as a person of ordinary skill in the art would have known. Id.
(citing, e.g., W.S. Ferguson et al., Current Treatment of Osteosarcoma,
19(3) CANCER INVEST. 292–315 (2001)2 (“Ferguson”)). Appellant points out
that the Specification subsequently discloses that:
The compounds of the invention or pharmaceutical compositions
thereof may be used for therapy, specifically in cancer
chemotherapy, i.e.[,] in a method for treatment of cancer, which
comprises administering a therapeutically effective amount of a
hemisulfate salt of the invention or pharmaceutical compositions
thereof to a subject in need of such treatment.

Id. (quoting Spec. 11).
Appellant contends that these disclosures of the Specification indicate
to one of ordinary skill in the art that Appellant was in possession of the
claimed invention at the time of filing. App. Br. 4. Appellant asserts that
this is particularly so because a skilled artisan would have been aware that
the drugs disclosed for combination with the claimed compositions include
three primary drugs approved for osteosarcoma therapy. Id.
We disagree. The Specification makes no express or implicit
disclosure of osteosarcoma. In the Non-Final Action, filed March 27, 2019,
the Examiner found that:
Cancer is not a single disease, or cluster of closely related
disorders. There are hundreds of proliferative diseases, which
have in common only some loss of controlled cell growth.

2 Not of record in this appeal.
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Cancers are highly heterogeneous at both the molecular
and clinical level, something seen especially in, for example, the
cancers of the breast, brain and salivary glands. They can occur
in pretty much every part of the body. For example, leukemia
is any malignant neoplasm of the blood-forming tissues.
Leukemia can arise from many different sources. These include
viruses such as EBV, which causes Burkitt’s lymphoma, and
HTLV-1, linked to certain T cell leukemias. Others are linked to
genetic disorders, such as Fanconi’s anemia, which is a familial
disorder, and Down’s syndrome. Other leukemias are caused by
exposure to carcinogens such as benzene, and some are actually
caused by treatment with other neoplastic agents. Still other
leukemias arise from ionizing radiation, and many are idiopathic.

Non-Final Act. 5–6. Because the genus of cancers is so capacious and
heterogeneous, the Specification’s mere disclosure of using the claimed
composition “in therapy, preferably in cancer chemotherapy,” (see Spec. 4)
is insufficient to demonstrate that Appellant was in possession of a “method
of treating … osteosarcoma,” as recited in the claims.
Nor are we persuaded by Appellant’s argument that, because the
Specification discloses three chemotherapeutic agents that are used in the
treatment of osteosarcoma as agents that can be co-administered with the
claimed composition, Appellant was in possession of a method of treating
osteosarcoma. The relevant disclosure in the Specification states:
Optionally, a pharmaceutical composition of the invention may
further comprise at least one additional therapeutic agent. In
specific embodiments the at least one additional therapeutic
agent may be selected from bactericides, antibiotics, antivirals,
antiseptics, antineoplastics, anticancer compounds such as
chemotherapeutic agents, antifungals, and/or anti-inflammatory
agents or other bioactive or therapeutic agents that are suitable
for human use, in particular anticancer compounds such as
chemotherapeutic agents. An anticancer drug such as a
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chemotherapeutic agent, may include but is not limited to
chemotherapeutic agents that comprise specific binding
members, proteins, nucleic acids or nucleic acid analogs (such
as, but not limited to antisense molecules, ribozymes, and
siRNAs), lipids, steroids, large molecules, small molecules, or
metals. The one or more anticancer drugs can comprise one or
more chemotherapeutic agents, such as but not limited to: nucleic
acids, in particular fluorinated nucleic acids (e.g.[,] 5-flurouracil
or an analog or prodrug thereof), antifolates (e.g.[,] pemetrexed,
raltitrexed, lometrexol), topoisomerase inhibitors (e.g.[,]
irinotecan, topotecan), antimetabolite drugs (e.g.[,]
methotrexate, gemcitabine, tezacitabine), 5-FU modulators,
alkylating agents (e.g.[,] cyclophosphamide, carmustine),
nucleic acid biosynthesis inhibitors (such as mitomycin,
anthracyclines (e.g.[,] epirubicin, doxorubicin), platinum
derivatives (e.g.[,] cisplatin, oxaliplatin, carboplatin),
microtubule disrupting drugs (e.g.[,] paclitaxel, docetaxel,
vinolrebine, vincristine), hormone blocking drugs (e.g.[,]
tamoxifen), inhibitors of kinases, including but not limited to
receptor and nonreceptor tyrosine kinases (e.g.[,] Iressa,
Tarceva, SU5416, PTK787, Gleevec), proteosome inhibitors
(e.g.[,] bortezomib), immune modulators (e.g.[,] levamisole),
anti-inflammatory drugs, vascularization inhibitors, cytokines
(e.g.[,] interleukins, tumor necrosis factors), and drugs that
inhibit the activity of cytokines, hormones, or receptors for
cytokines or hormones (e.g.[,] the anti- VEGF antibody
bevacizumab or “Avastin”). Anticancer drugs may also include
monoclonal antibodies, such as but not limited to monoclonal
antibodies that bind cytokines, hormones, or hormone receptors
(e.g.[,] antibodies that block activation of EGF or VEGF growth
factors, such as Avastin, Erbitux, herceptin), etc.

Spec. 11. This large and exceedingly diverse genus of additional active
agents, which incidentally discloses three drugs used in the treatment of
osteosarcoma, is insufficient to “reasonably convey[ ] to those skilled in the
art that the inventor had possession of the claimed subject matter as of the
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filing date,” particularly in view of the highly diverse constellation of cancer
causes and mechanisms. Ariad, 598 F.3d at 1351. We consequently affirm
the Examiner’s rejection of these claims.

B. Rejection of claim 18 for lack of enablement
Issue
Appellant argues that the Examiner erred in finding claim 18 lacks
enablement because the Examiner has failed to meet the burden of showing
that the Specification is not commensurate in scope with the claims. App.
Br. 5 (citing MPEP § 2164.04).

Analysis
The Examiner finds that claim 18 contains subject matter that was not
described in the Specification in such a way as to enable one skilled in the
art to which it pertains, or with which it is most nearly connected, to use the
invention. Final Act. 2. The Examiner points to the Non-Final Action, in
which the relevant factors set forth in In re Wands, 858 F.2d 731, 737 (Fed.
Cir. 1988), were reviewed. With respect to Wands factor 1, the breadth of
the claims and, specifically, the scope of the diseases covered, we have
already explained that the Examiner finds that cancers are a highly diverse
genus, both with respect to causes (many of which are unknown),
pathologies, target tissues, malignancy, etc. See Non-Final Act. 5–6.
With respect to Wands factor 2, the nature of the invention and
predictability in the art, the Examiner points to In re Hozumi, 226 USPQ 353
(Comm’r Pat., 1985) as finding the “fact that the art of cancer chemotherapy
is highly unpredictable,” and notes that the predecessor to our reviewing
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court has held that “the scope of enablement varies inversely with the degree
of unpredictability of the factors involved.” Non-Final Act. 6–7 (quoting In
re Fisher, 427 F.2d 833, 839 (C.C.P.A. 1970)).
With respect to Wands factor 3, the direction or guidance provided by
the Specification, the Examiner finds that the guidance is very limited,
noting that the Specification does not indicate how one skilled in the art can
reliably identify a subject that will develop cancer, or whether prevention
has occurred. Non-Final Act. 7. The Examiner finds that prevention outside
of the infectious diseases is generally not enabled. Id.
With respect to Wands factor 4, state of the prior art, the Examiner
finds that there is no evidence of record that the claimed composition has
been used in the prevention of cancer. The Examiner also finds that there
are no working examples in the Specification demonstrating the prevention
of cancer generally (Wands factor 5), and that the skill of those in the art is
such that it is known that there never has been a compound capable
of treating cancers generally (Wands factor 6). Id. (citing Hozumi, 226
USPQ at 355 (finding that “[i]n spite of the vast expenditure of human and
capital resources in recent years, no one drug has been found which is
effective in treating all types of cancer”). The Examiner therefore finds that
the balance of the Wands factors weighs against enablement of claim 18. Id.
at 7–8.
Appellant argues that the Examiner has adduced no evidence to
demonstrate why a person skilled in the art would not be able to identify
subjects in need of reduction of risk of cancer, or how one would determine
whether the risk of cancer has been reduced. App. Br. 5. Appellant asserts
that determining enablement requires, in addition to the disclosures of the
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Specification, taking into account the knowledge of one of ordinary skill in
the art. Id. (citing, e.g., DeGeorge v. Bernier, 768 F.2d 1318, 1323 (Fed.
Cir. 1985)). Appellant contends that it is within the ability of a person of
ordinary skill in the art to identify patients in need of risk reduction or
patient populations who are at an elevated risk, e.g., patients who have been
exposed to carcinogens, certain viruses, asbestos, cigarette smoke, etc. Id.
With respect to determining whether the risk of cancer has been
reduced, Appellant notes that such a step is not recited in the claim. App.
Br. 5. Appellant argues that the claims do not recite any such determination
and, therefore, no such step requires enablement. Id. at 5–6. Nevertheless,
argues Appellant, determining whether the risk of cancer has been reduced
or not, e.g., in a patient population, is known in the art, and the Examiner has
adduced no evidence to the contrary. Id. at 6.
Finally, Appellant argues that the Specification provides express
guidance on how to achieve the reduction or lowering of risk of cancer, e.g.,
by providing clear guidance on: (1) routes of administration; (2) dosage
information; (3) examples of specific dosage forms; (4) preclinical/clinical
results; (5) animal data that includes high dose levels safety determination;
and (6) data on humans, including cancer patients, determining the
pharmacokinetic and pharmacodynamic properties of (6R)-5,10-CH2-THF
hemisulfate. App. Br. 6 (citing Spec. 12–14, Ex. 5, Ex. 6).
We are not persuaded. Section 112 requires that the patent
specification enables “those skilled in the art how to make and use the full
scope of the claimed invention without ‘undue experimentation’” in order to
extract meaningful disclosure of the invention and, by this disclosure,
advance the technical arts. Koito Mfg. Co., Ltd. v. Turn-Key-Tech, LLC, 381
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F.3d 1142, 1155 (Fed. Cir. 2004) (quoting Genentech, Inc. v. Novo Nordisk
A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997)). Furthermore:
The scope of [patent] claims must be less than or equal to the
scope of the enablement. The scope of enablement, in turn, is that
which is disclosed in the specification plus the scope of what
would be known to one of ordinary skill in the art without undue
experimentation.

Nat’l Recovery Techs., Inc. v. Magnetic Separation Sys., Inc., 166 F.3d
1190, 1196 (Fed. Cir. 1996); see also In re Goodman, 11 F.3d 1046, 1050
(Fed. Cir. 1993) (holding that “the specification must teach those of skill in
the art ‘how to make and how to use the invention as broadly as it is
claimed’”). Furthermore, “the scope of the claims must bear a reasonable
correlation to the scope of enablement provided by the specification to
persons of ordinary skill in the art.” In re Fisher, 427 F.2d 833, 839
(C.C.P.A. 1970).
Claim 18 recites, in relevant part: “A method for lowering the risk of
cancer, comprising….” As such, the method relates to lowering the risk of
all forms of cancer. The scope of enablement, then, must at least match the
scope of the claims, i.e., the disclosures of the Specification should inform a
person of ordinary skill in the art how to determine that administration of the
claimed composition risk of cancer “lower[s] the risk of cancer” for all
cancers. The Specification makes no such disclosure. Indeed, and as the
Examiner has shown by analysis of the Wands factors, the fact that cancers
can have a very wide variety of causes (many as yet unknown) and effects,
as well as the very high level of unpredictability of the art with respect to the
causes of cancers, makes enabling “lowering the risk of [all] cancer[s]”
virtually impossible. Appellant’s argument that such knowledge would be
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within the skill of an ordinary artisan is not supported by any evidence of
record concerning the knowledge or level of skill in the art, and therefore
constitutes no more than attorney argument, to which we accord little
probative value. See In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997).
Finally, Appellant’s arguments that the Specification discloses
methods of making and administering the drug safely does not demonstrate
that administering the drug in accordance with the requirements of the claim
and the disclosures of the Specification actually “lower[ ] the risk of [all]
cancer[s].” See App. Br. 6. We consequently agree with the Examiner that
claim 18 is not enabled by Appellant’s Specification, and we affirm the
Examiner’s rejection.

CONCLUSION
The rejection of claim 18 as unpatentable under 35 U.S.C. § 112(a)
for lack of written description is reversed.
The rejection of claims 24 and 26 as unpatentable under 35 U.S.C.
§ 112(a) for lack of written description is affirmed.
The rejection of claims 18 as unpatentable under 35 U.S.C. § 112(a)
for lack of enablement is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).

AFFIRMED

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Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
18, 24, 26 112(a) Written Description 24, 26 18
18 112(a) Enablement 18
Overall
Outcome
18, 24, 26