NESTEC S.A.

Patent Trials and Appeals Board

Mar 22, 2022

2021002876 (P.T.A.B. Mar. 22, 2022)

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. 15/892,078 02/08/2018 Christophe Moinard 3712036-03080 6140 29157 7590 03/22/2022 K&L Gates LLP-Nestec S.A. P.O. Box 1135 Chicago, IL 60690 EXAMINER BAKSHI, PANCHAM ART UNIT PAPER NUMBER 1623 NOTIFICATION DATE DELIVERY MODE 03/22/2022 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): USpatentmail@klgates.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CHRISTOPHE MOINARD, GABRIELLE VENTURA, DENIS BREUILLE, CHRISTIAN DARIMONT-NICOLAU, and LUC CYNOBER Appeal 2021-002876 Application 15/892,078 Technology Center 1600 Before JEFFREY N. FREDMAN, JOHN E. SCHNEIDER, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims to a method of treating hyperglycemia by administering a therapeutically effective amount of citrulline and leucine as being obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 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 Société Des Produits Nestlé S.A. (Appeal Br. 2.) Appeal 2021-002876 Application 15/892,078 2 STATEMENT OF THE CASE Appellant’s Specification states that “[i]nsulin resistance is associated with a number of disease states and conditions and is present in approximately 30-40% of non-diabetic individuals.” (Spec. 3.) The conditions include pre-diabetes which “is a state of abnormal glucose tolerance characterized by either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG).” (Id.) “Patients with pre-diabetes are insulin resistant and are at high risk for future progression to overt Type 2 diabetes.” (Id.) The Specification states that the inventors surprisingly and unexpectedly found that administration of citrulline and leucine (or a metabolite thereof) has a synergistic effect and is able to reduce fasting glucose levels and fasting insulin plasma levels below the level of reduction obtained with individual administration of citrulline or leucine. (Id. ¶ 4.) Claims 1, 4-6, and 8-14 are on appeal.2 Claim 1, reproduced below, is illustrative of the claimed subject matter: 1. A method of treating a condition selected from the group consisting of prediabetes, metabolic syndrome, hyperglycemia, and diabetes in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of citrulline and a therapeutically effective amount of leucine, wherein the subject is administered a weight-based dose of the citrulline and the leucine. (Appeal Br. 14.) 2 Claim 2 remains pending but is withdrawn from consideration as being drawn to a non-elected species. Appeal 2021-002876 Application 15/892,078 3 In response to a species election requirement, Appellant elected hyperglycemia as the condition to be treated. (See Final Action 2.) Accordingly, as to the appealed obviousness rejection, we limit our analysis to the patentability of the elected species and the extent to which the rejected claims read on it. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (BPAI 1987). The prior art relied upon by the Examiner is: Name Reference Date Petrus US 8,017,657 B1 Sept. 13, 2011 Greenberg et al. WO 2012/143403 A1 Oct. 26, 2012 Salim Bastaki Diabetes mellitus and its treatment, 13 Int. J. Diabetes & Metabolism, 111-34 2005 The following ground of rejection by the Examiner is before us on review: Claims 1, 4-6, and 8-14 under 35 U.S.C. § 103 as unpatentable over Petrus, Greenberg, and Bastaki. DISCUSSION The Examiner found that Petrus teaches a method of treating “diseases related to endothelial dysfunction such as hypertension, diabetes (causing hyperglycemia), cardiovascular diseases,” which method involves orally administering a composition that includes citrulline and leucine. (Final Action 4.) The Examiner further found that Example 10 of Petrus teaches a composition that includes 50 mg of citrulline and 25 mg of leucine. (Id.) The Examiner found that Petrus does not teach: the end result of the process such as reduction in fasting sugar Appeal 2021-002876 Application 15/892,078 4 level, decrease in insulin resistance etc.; process may comprise administration of other treatment with agents such as insulin (protein) etc.; and total amount of dose or a weight-based dose, such as g/Kg of the instant claims. (Id. at 5.) The Examiner found that Greenberg teaches a composition for oral administration that can be used to treat “diseases such as glucose tolerance, insulin sensitivity etc.,” which composition includes “an effective amount of alpha-hydroxyisocaproic acid (HIC) (metabolite of leucine) and an effective amount of citrulline.” (Final Action 4.) The Examiner noted that Greenberg teaches that a “subject in need” may be provided with 0.15-10 g per day of HIC, and 1-15 g citrulline per day that may be dosed on a g/Kg basis. (Id.) The Examiner found, however, that Greenberg does not teach the end result of the process such as reduction in fasting sugar level, decrease in insulin resistance etc.; process may comprise administration of other treatment with agents such as insulin (protein) etc.; dose of 1g/Kg of citrulline and 1g/Kg of leucine. (Id. at 5.) The Examiner relied on Batsaki for its teaching of treating diabetes mellitus “with insulin (a protein) or oral therapeutic agents such as sulfonyl urea, thazolidine etc.” and noted that “diabetes mellitus causes hyperglycemia” (Id.) According to the Examiner, from the foregoing teachings, it would have been obvious to one of ordinary skill in the art that (1) the treating method may be practiced with both leucine or its metabolite HIC (as leucine once consumed will produce HIC as a metabolite), absent any evidence to the contrary; (2) the dose given to humans, animals etc. is customarily given in a weight based form, i.e. dependent on weight of the subject, such as mcg/Kg, mg/Kg, g/Kg etc. in fixed doses; (3) the Appeal 2021-002876 Application 15/892,078 5 composition of Petrus may be given one time (of two or three tablets of the composition) or several times in a day as Greensburg teaching also suggests that it is safe to give higher doses of metabolite of leucine and citrulline and (4) dose may be adjusted based on the age, sex and condition of the subject absent any evidence to the contrary. (Id. at 6.) Regarding achieving a reduction in fasting sugar level or a decrease in insulin resistance, the Examiner stated that such would have been an obvious result since Petrus teaches that the composition of example 10 (columns 15-16) is effective in treating diseases related to endothelial dysfunction such as hypertension, diabetes, cardiovascular diseases etc. and Greenberg teaches that the composition is effective in treating diseases related to metabolism such as glucose tolerance, insulin sensitivity etc. (related to diabetes). (Id. at 7.) We do not agree with certain of the Examiner’s findings, and as a consequence, we also do not agree with the Examiner’s conclusion of obviousness. “[T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting a prima facie case of unpatentability. If that burden is met, the burden of coming forward with evidence or argument shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). We do not agree with the Examiner that Petrus teaches that citrulline and leucine will treat diabetes. Petrus teaches a method of treating and/or preventing endothelial dysfunction. (Petrus Abstr.) Petrus characterizes endothelial dysfunction as follows: Endothelial dysfunction is characterized by a loss of barrier function and an infiltration of cellular material into the vascular wall and loss of physiological vascular tone. There is a loss of Appeal 2021-002876 Application 15/892,078 6 nitric oxide mediated physiological vasodilation, increased endothelial adhesion and migration of leucocytes and macrophages into the subendothelial vascular wall. (Id. at 1:40-45.) Petrus further notes that triggering events for endothelial dysfunction are “[h]ypoxia, shear forces and oxidative stress.” (Id. at 1:46- 47.) Petrus states that “[t]he vascular endothelium modulates blood vessel tone by secreting a variety of dilating and constricting substances” and that “[t]hese agents not only control and alter vascular tone, but also can affect platelet adhesion and aggregation, influence thrombogenicity of the blood, and participate in cell proliferation and the development and progression of atherosclerosis.” (Id. at 2:21-25.) Petrus further indicates that “disorders associated with endothelial dysfunction may occur in any endothelial cells and include; hypertension, atherosclerosis, diabetes, immune system dysfunction, infections, inflammations, macular degeneration, cardiovascular disease and stroke.” (Id. at 1:47-51.) However, Petrus does not teach that any of the foregoing diseases are caused by endothelial dysfunction. Moreover, Petrus does not teach that all of the named compounds it discusses will be useful to treat all the diseases that it lists as being associated with endothelial dysfunction. Nor does the Examiner point to anything in Petrus to indicate any of the compounds mentioned would inhibit or prevent the presence of too much sugar in the blood, which is what leads to hyperglycemia. The only mention of hyperglycemia in Petrus is the following: The combined effects of Vitamin C and E prevented endothelial dysfunction during transient hyperglycemia after oral glucose loading in healthy subjects. (Id. at 11:13-15.). Appeal 2021-002876 Application 15/892,078 7 Moreover, there is nothing even similar to Petrus’s disclosure of effects seen with the use of Vitamin C and E for citrulline and leucine. We provide our further reasoning below as to why we do not conclude that the disclosure in Petrus would lead one to conclude that any amount of citrulline and leucine would be effective to treat hyperglycemia. Petrus states that an object of the invention is to incorporate a nonsteroidal anti-inflammatory agent (NSAID) such as acetylsalicylic acid (ASA, aspirin), “to provide pain relief and anti-inflammatory and anti- thrombotic benefits to prevent and treat endothelial dysfunction.” (Petrus 8:41-44.) In addition, Petrus explains that glucosamine, in a variety of forms, is another important part of the invention because (1) it helps form the electrostatic barrier in the glucoaminoglycan (GAG) layer of the GI tract “located in the pre-endothelial and sub-endothelial area in the arterial network” and helps to improve GI and vascular inflammatory disorders (id. at 8:45-66, 9;41-43) and (2) is “an essential component of cell membranes and cell surface proteins as well as interstitial structural molecules that hold cells together” and has been reported to be used in a composition for the repair of connective tissue and for treating osteoarthritis (id. at 9:1-12, 46- 51). Petrus also indicates that including a zinc compound is an object of the invention, as it is known (1) to have gastroprotective effects, such as preventing mucosal ulcerations (id. at 9:53-64), and (2) an inhibitory effect on the release of histamine from mast cells, which cells are present in atherosclerotic plaques (id. at 9:65-10:1-2, 12-14). Appeal 2021-002876 Application 15/892,078 8 Petrus also explains that Zinc and glucosamine can help alleviate problems caused by the administration of NSAIDs, e.g., aggravating or initiating colitis type disorders, as well as tinnitus. (Id. at 8:45-50, 9:48-52, 10:15-25, 38-42.) After the extensive discussion of the foregoing compounds, Petrus notes that people are known to add dietary supplements to their diet and states that: Dietary supplements . . . have been associated with improving exercise tolerance and recovery, lowering blood pressure and improving endothelial dysfunction and immune dysfunction. (Petrus 10:57-64.) Then Petrus lists a number of known dietary supplements-e.g., vitamins, minerals, amino acids, and fatty acids-, and within that list are citrulline and leucine, as are Vitamin C and E. (Petrus 10:65-11:7.) Petrus indicates that citrulline is a “vasoprotective supplement[]” and that it “can be converted into nitric oxide” and that it “is transformed in the kidneys to arginine and [is] necessary for endothelial health.” (Petrus 11:17- 18; 12:3-5.) However, nothing in Petrus links the use of citrulline to prevention of hyperglycemia, such as a description of a process that leads to hyperglycemia that citrulline’s vasoprotective activity or conversion to nitric oxide or conversion to arginine would be important in preventing. The disclosure regarding leucine is even less than that for citrulline. It is simply stated to be a supplement that is a branched-chain amino acid. (Id. at 11:4.) In contrast, as we noted above, Petrus specifically teaches Vitamins C and E have been shown to have positive effects in diabetics and or in hyperglycemia. In particular, Petrus states: Appeal 2021-002876 Application 15/892,078 9 Vitamin C improved vascular dysfunction in diabetics. The combined effects of Vitamin C and E prevented endothelial dysfunction during transient hyperglycemia after oral glucose loading in healthy subjects (Id. at 11:12-15.) Notably, however, even as to these supplements, Petrus does not teach that diabetes or hyperglycemia itself was treated, just that endothelial or vascular dysfunction that can presumably result from these diseases/disorders was prevented or improved. Thus, although it is true that Petrus provides an explicit example of a composition that includes citrulline and leucine (Petrus Example 10), we do not agree with the Examiner that Petrus can be fairly said to teach the use of citrulline and leucine in any composition in any amount to treat diabetes, much less hyperglycemia. As Appellant states, supported by the Declaration Under 37 § 1.132 of Denis Breuillé3, there is “no teaching in Petrus [that]would have suggested to one skilled in this art that citrulline and leucine could have any effect on hyperglycemia.” (Appeal Br. 6; Breuillé Declaration ¶ 4.) Greenberg also does not teach that citrulline or leucine would have any benefit in treating diabetes or hyperglycemia. As Appellant and the Declarant explain, Greenberg teaches compositions for muscle protein synthesis and reduction in lean body mass leading to metabolic instability. (Greenberg Abstr. ¶ 3; Appeal Br. 7; Breuillé Declaration ¶ 6.) The only mention of diabetes is in paragraph 113 of Greenberg, in which it is stated that phytochemicals appear to play beneficial roles in diabetes. (Greenberg ¶ 113.) Consequently, Greenberg also does not teach a method in which a 3 The Declaration of Dr. Breuillé is dated July 22, 2019. Appeal 2021-002876 Application 15/892,078 10 composition is provided with an effective amount of citrulline or leucine to treat diabetes or hyperglycemia. Bastaki does not cure the deficiencies noted. In light of the foregoing, we do not affirm the Examiner’s rejection of the claims as being obvious over the teachings of Petrus, Greenberg, and Bastaki. As noted above, we limit our analysis to the patentability of the elected species, hyperglycemia, and the extent to which the rejected claims read on it. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 4-6, 8-14 103 Petrus, Greenberg, Bastaki 1, 4-6, 8-14 REVERSED