MERCK & CIEDownload PDFPatent Trials and Appeals BoardMar 19, 20212020004905 (P.T.A.B. Mar. 19, 2021) Copy Citation 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. Appeal 2020-004905 Application 16/212,056 2 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. Appeal 2020-004905 Application 16/212,056 3 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 Appeal 2020-004905 Application 16/212,056 4 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 Appeal 2020-004905 Application 16/212,056 5 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 Appeal 2020-004905 Application 16/212,056 6 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 Appeal 2020-004905 Application 16/212,056 7 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, Appeal 2020-004905 Application 16/212,056 8 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. Appeal 2020-004905 Application 16/212,056 9 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 Appeal 2020-004905 Application 16/212,056 10 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 Appeal 2020-004905 Application 16/212,056 11 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 Appeal 2020-004905 Application 16/212,056 12 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 Appeal 2020-004905 Application 16/212,056 13 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 Appeal 2020-004905 Application 16/212,056 14 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 Appeal 2020-004905 Application 16/212,056 15 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 Appeal 2020-004905 Application 16/212,056 16 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 Copy with citationCopy as parenthetical citation