Fr¿d¿ric Sedel et al.Download PDFPatent Trials and Appeals BoardMay 14, 202013639752 - (D) (P.T.A.B. May. 14, 2020) 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. 13/639,752 11/14/2012 Frédéric Sedel 4279-102 9412 6449 7590 05/14/2020 ROTHWELL, FIGG, ERNST & MANBECK, P.C. 607 14TH STREET, N.W. SUITE 800 WASHINGTON, DC 20005 EXAMINER PARAD, DENNIS J ART UNIT PAPER NUMBER 1612 NOTIFICATION DATE DELIVERY MODE 05/14/2020 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): PTO-PAT-Email@rfem.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte FRÉDÉRIC SEDEL and AGNÈS BELLANGER __________ Appeal 2019-005635 Application1 13/639,752 Technology Center 1600 __________ Before DONALD E. ADAMS, ERIC B. GRIMES, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a biotin composition for oral administration, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE Biotin is a “water-soluble vitamin which is naturally found in many foods.” (Spec. 1.) “In mammals, biotin acts as a cofactor for four 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as Assistance Publique-Hopitaux De Paris and Medday Pharmaceuticals. (Appeal Br. 2.) Appeal 2019-005635 Application 13/639,752 2 metabolism” enzymes and “it has also been shown that biotin can regulate the expression of many genes.” (Id. at 1–2.) Commercially available oral dosage forms of biotin exist. (Id. at 4.) However, many contain other active ingredients and “less than 1 mg of biotin.” (Id.) One dosage form “contains only biotin, as active ingredient” but includes only “5 mg of biotin per unit dose.” (Id.) Appellant’s invention is an oral dosage form of biotin that provides “a large amount of biotin for each unit dose.” (Id.) Claims 23, 25–27, 29, and 30 are on appeal. Claim 23 is representative and reads as follows: 23. A composition for oral administration in unit dosage form, wherein said composition is formulated for human administration and consists of at least 100 mg biotin per unit dose as sole active ingredient, and one or more excipients, wherein said unit dosage form is a gel capsule, a tablet, a film- coated tablet, a lozenge or a pill. (Appeal Br. 26.) The prior art relied upon by the Examiner is: Name Reference Date McCarty US 5,929,066 July 27, 1999 A. Reddi et al., Biotin Supplementation Improves Glucose and Insulin Tolerances in Genetically Diabetic KK Mice, 42 Life Sciences 1323–30 (1988) C. Revilla-Monsalve et al., Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia, 60 Biomedicine & Pharmacotherapy 182–185 (2006) Diverse Populations Collaborative Group, Weight-Height Relationships and Body Mass Index: Some Observations From the Diverse Populations Collaboration, 128 Am. J. Phys. Anthropol. 220–29 (2005) (“DPCG”) FMC, Avicel® PH Microcrystalline Cellulose, Material Safety Data Sheet, 2014. Appeal 2019-005635 Application 13/639,752 3 The following ground of rejection by the Examiner is before us on review: Claims 23, 25–27, 29, and 30 under 35 U.S.C. § 103(a) as unpatentable over Revilla-Monsalve, Reddi, McCarty, DPCG, and FMC. DISCUSSION The Examiner finds that Revilla-Monsalve teaches a pharmaceutical composition that contains 5 mg of biotin as the sole active ingredient, as well as including the excipient Avicel® in an oral administration dosage form that is used to reduce hyperglycemia and hypertriglyceridemia in a “diabetic state.” (Non-Final Action2 3–4, 6.) The Examiner finds that FMC teaches that Avicel® is microcrystalline cellulose (MCC). The Examiner further finds that Revilla-Monsalve “cited a study of ‘rats consuming a diet containing 100 mg/kg of biotin during 21 days’ (page 184, col 2, third full paragraph).” (Ans. 9.) The Examiner recognizes that the amount of biotin exemplified in Revilla-Monsalve is less than the minimum amount required by the claims. (Non-Final Action 4.) However, the Examiner concludes that it would have been obvious to optimize the amount of biotin in the Revilla-Monsalve dosage form to at least 100 mg of biotin in light of the combined teachings of Reddi, McCarty, and DPCG. (Id. at 4–6; Ans. 11.) In particular, the Examiner finds that Reddi, an article cited in Revilla-Monsalve, “discovered that high dose biotin treatment[, 2mg of biotin/kg,] is also useful for non- insulin dependent diabetes by lowering post-prandial glucose levels and 2 The Non-Final Action is dated October 1, 2018. Appeal 2019-005635 Application 13/639,752 4 improving tolerance to glucose and insulin resistance” besides being useful for treating insulin-dependent diabetes. (Id.) The Examiner relies on DPCG for its teaching of average weight in human populations and concluding that the human equivalent dosage in Reddi is about 153 mg for males and about 134 mg for females.3 (Non-Final Action 5, 6.) The Examiner further finds that “McCarty teaches a unit dosage” of biotin for oral administration of up to 200 mg per day in human patients to treat diabetes. (Id. at 4.) In addition, McCarty teaches “no side effects or toxicities were noted in clinical studies with oral biotin intakes of up to 200 mg daily.” (Id. at 4–5.) In light of the foregoing, the Examiner concludes that the prior art teaches that “the dosage amount of biotin is a result- effective variable” for treating diabetes (Non-Final Action 7) and that, in combination, the prior art “provides a motivation and reasonable expectation of success for formulating high dosages of biotin for treating diabetes” of at least 100 mg (Ans. 10; Non-Final Action 6–7) and that doing so is a matter of “determining optimum or workable ranges by routine experimentation” (Non-Final Action 5–6; Ans. 12). Regarding McCarty, which the Examiner acknowledges also teaches administering chromium in a range of from about 50–1000 micrograms per day (Ans. 13), the Examiner explains “whether or not additional actives are taught by McCarty, this does not teach away from the fact that the reference suggests that administering higher doses of biotin [as compared to the dosage of Revilla-Monsalve] is well known and has pharmacological utility, 3 The Examiner arrived at this amount by multiplying the dosage (mg/kg) in Reddi by the average weight for human males or females. (Id.) Appeal 2019-005635 Application 13/639,752 5 which is dose-dependent.” (Ans. 14.) The Examiner explains that “[t]here is no evidence in the cited references or in any of Appellant’s data that teach away from formulating a unit dosage form having a high dose of biotin, including 100 mg or more.” (Ans. 14.) The Examiner further finds that the Specification “makes no mention of the criticality of 100 mg or more biotin.” (Ans. 7.) We agree with the Examiner’s conclusion of obviousness, but rely only on McCarty. In affirming a multiple reference rejection under 35 U.S.C. § 103, the Board may rely on fewer than all of the references relied on by the Examiner in an obviousness rationale without designating it as a new ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961). McCarty teaches two compounds “administered orally or parenterally in daily dosages which provide between 50 and 1,000 μg of chromium and between 25 μg and 200 mg biotin” for treating Type II diabetes. (McCarty Abstract.) In addition, as the Examiner noted, McCarty teaches a preferred dosage range for biotin in the combination therapy is between 1 mg to 100 mg. (Id. at 3: 9–12.) McCarty teaches that “[f]or oral administration, the chromic picolinates and biotin may be provided as a tablet . . . [or] hard or soft capsule.” (Id. at 3:13–16.) Regarding the oral dosage form, McCarty further teaches that the composition is a pharmaceutically acceptable composition and may include excipients, including “lubricating agents such as magnesium stearate, stearic acid or talc.” (Id. at 3:16–34.) Furthermore, as the Examiner noted, McCarty teaches that no side effects or toxicities were noted in previous clinical studies with oral biotin intakes of up to 200 mg daily. (Id. at 1:63–66.) Appeal 2019-005635 Application 13/639,752 6 Although McCarty does teach that the amounts of chromium and biotin are selected so that the chromium and biotin together “provide a greater than additive effect” in treating diabetes (id. Abstract; Appeal Br. 23 (“McCarty stresses the importance of the synergistic effects of chromic tripicolinate and biotin.”)), McCarty does not require that these two compounds must be administered as a combination of active ingredients in a single dosage form for combination therapy to be achieved. (Compare McCarty 2:34–47 (noting the compounds individually), with id. at 2:48–50 (noting the use of the two compounds combined in a pharmaceutical composition).) Indeed, McCarty suggests that commercially available forms of these drugs sold separately could be used in the method so long as they were used in the dosage range. (Id. at 3:1–13.) The claims of McCarty indicating that biotin is administered orally (claim 7) and chromic tripicolinate is administered parenterally (claim 8) further support the conclusion that McCarty does not require biotin and chromic tripicolinate to be combined into a single dosage form to administer the combined therapy. Thus, we do not find persuasive Appellant’s argument that McCarty “suggests only a combination of biotin and chromic tripicolinate” as a single dosage form (Reply Br. 10; Appeal Br. 23–24). We note that taking the minimum amount of pills is generally more desirable for a patient than taking numerous pills to obtain the same dosage amount. With that, and McCarty’s suggestion that 100 mg is part of a preferred range for administration to a diabetic patient but that up to 200 mg can be used, and its teaching that dosage forms can be tablets or capsules, making a dosage form of biotin in a capsule or tablet to include 100 mg biotin and at least one excipient would have been obvious to one of ordinary Appeal 2019-005635 Application 13/639,752 7 skill in the art with a reasonable expectation of success.4 “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the . . . workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955). “It is well-established that the Board is free to affirm an examiner’s rejection so long as ‘appellants have had a fair opportunity to react to the thrust of the rejection.”’ In re Jung, 637 F.3d 1356, 1365 (Fed. Cir. 2011) (citing In re Kronig, 539 F.2d 1300, 1302–03 (CCPA 1976)). We find this to be the case given the arguments Appellant made and discussed below. Appellant argues that McCarty only explicitly discloses a 3 mg unit dosage form of biotin (Appeal Br. 18), much like the many prior art articles cited by Appellant describing unit dosages of biotin administered (Appeal Br. 19–21), and is another reason, combined with the fact that it “discloses an extraordinarily broad range of daily dosages (to be combined with chromic tripicolinate),” that McCarty does not provide a motivation to 4 Regarding the requirement of claims 25 and 29 that the excipient be talc or MCC, we note that talc is a lubricating agent taught in McCarty. The selection of this excipient would have been obvious to one having ordinary skill in the art. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 335 (1945) (“Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put into the last opening in a jig-saw puzzle. It is not invention.”); see also Merck & Co. Inc. v. Biocraft Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). Furthermore, Revilla-Monsalve teaches that it was known in the art that biotin is compatible with an excipient such as MCC and in an oral dosage form. It would have been obvious to include MCC in an oral dosage form of 100 mg of biotin that includes an excipient suggested by McCarty. Appeal 2019-005635 Application 13/639,752 8 prepare a high-unit dose composition “wherein biotin is the sole active ingredient” (id. at 19). We disagree with Appellant’s conclusion. The prior art referenced in McCarty using low doses of biotin, at or below the range of Revilla-Monsalve, along with the other prior art studies Appellant cites, does not detract from McCarty’s teaching that a daily dosage of up to 200 mg of biotin, and preferably up to 100 mg, is within the scope of McCarty’s teachings. That McCarty itself does not make such a composition (Reply Br. 4) does not evidence non-obviousness of such a unit dosage form. “It is well settled that a prior art reference is relevant for all that it teaches to those of ordinary skill in the art.” In re Fritch, 972 F.2d 1260, 1264 (Fed. Cir. 1992). We also do not find persuasive Appellant’s argument that McCarty teaches away from an oral dosage form of biotin as the only active ingredient and at a high dosage level (Appeal Br. 24; Reply Br. 11). A reference teaches away from a claimed invention if it “criticize[s], discredit[s], or otherwise discourage[s]” modifying the reference to arrive at the claimed invention. In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). The fact that McCarty promotes the use of biotin together with chromic tripicolinate is not evidence that McCarty criticizes, discredits, or discourages a single dosage form of biotin. And, indeed, as discussed above McCarty suggests combination therapy in which each compound is administered as a separate dosage form. Moreover, the fact that McCarty does not provide an exemplification of a dosage at the high end of the disclosed range, does not evidence criticism, discrediting or discouragement from making a single dosage form in this disclosed acceptable range. Appeal 2019-005635 Application 13/639,752 9 Appellant argues that “the present application . . . disclose[s] unexpected advantages of high-unit dose biotin compositions” (Appeal Br. 22) and “McCarty provides no examples whatsoever describing the actual production of a composition, much less its effectiveness upon administration to a patient” (id. at 23) which supports a conclusion that “a person of ordinary skill in the art would not have been motivated to, nor would have had a reasonable expectation of successfully formulating a unit dose of at least 100 mg biotin as sole active ingredient” (id. at 24). We do not find Appellant’s argument persuasive of non-obviousness. We have addressed motivation above regarding a reason to make a single dose formulation of biotin that has at least 100 mg biotin therein. That McCarty does not provide an example of the effectiveness of such a composition is not persuasive of non-obviousness of the composition, which has no efficacy limitations. See Catalina Mktg. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002) (“[T]he patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure.”). Furthermore, regarding a reasonable expectation of success, the prior art teaches that oral dosage forms of biotin are known and the Examiner’s position is that one of ordinary skill in the art using routine experimentation would have found it obvious to formulate and achieve an oral dosage form that includes 100 mg biotin. (See, e.g., Ans. 8, 10.) Appellant does not provide any argument or evidence that formulating such a dosage form would have required extraordinary skill or would have been unexpectedly difficult. Rather, Appellant provides the Declaration of Dr. Frédéric Sedel that “demonstrates the significant unexpected advantages of administering Appeal 2019-005635 Application 13/639,752 10 high-dose biotin to patients suffering from multiple sclerosis.” (Appeal Br. 22.) Such evidence regarding unexpected effectiveness in use with multiple sclerosis patients does not establish the formulation containing 100 mg biotin itself was unexpectedly achieved. Thus, we affirm the Examiner’s rejection of claims 23, 25–27, 29, and 30 under 35 U.S.C. § 103(a) as unpatentable over Revilla-Monsalve, Reddi, McCarty, DPCG, and FMC. DECISION SUMMARY Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 23, 25–27, 29, 30 103 Revilla-Monsalve, Reddi, McCarty, DPCG, FMC 23, 25–27, 29, 30 TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED Copy with citationCopy as parenthetical citation