Ex Parte Buck et alDownload PDFPatent Trials and Appeals BoardMay 7, 201913840825 - (D) (P.T.A.B. May. 7, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/840,825 03/15/2013 23117 7590 05/09/2019 NIXON & V ANDERHYE, PC 901 NORTH GLEBE ROAD, 11 TH FLOOR ARLINGTON, VA 22203 FIRST NAMED INVENTOR Neil Robert Buck 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. ES-4662-2801 5107 EXAMINER QAZI, SABIHA NAIM ART UNIT PAPER NUMBER 1621 NOTIFICATION DATE DELIVERY MODE 05/09/2019 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): PTOMAIL@nixonvan.com pair_nixon@firsttofile.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte NEIL ROBERT BUCK, WOUTER CLAERHOUT, BRUNO H. LEUENBERGER, ELISABETH STOECKLIN, KAI URBAN, and SWEN WOLFRAM 1 Appeal2018-004569 Application 13/840,825 Technology Center 1600 Before RICHARD M. LEBOVITZ, JOHN G. NEW, and ROBERT A. POLLOCK, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 Appellants identify DSM IP Assets B.V. as the real party-in-interest. App. Br. 3. Appeal2018-004569 Application 13/840,825 SUMMARY Appellants file this appeal under 35 U.S.C. § I34(a) from the Examiner's Final Rejection of claims 1, 7-13, 15-23, and 25 as unpatentable under 35 U.S.C. § I03(a) as being obvious over the combination of Chung et al. (WO 2007/020042 Al, February 22, 2007) ("Chung"), Krammer et al. (US 2007/0082089 Al, April 12, 2007) ("Krammer"), Bishop et al. (US 8,361,488 B2, January 29, 2013) ("Bishop"), A.G. Pittas et al., The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults, 30(4) DIABETES CARE 980-86 (2007) ("Pittas"), and R. Scragg et al., Serum 25-Hydroxyvitainin DJ Levels Decreased in Impaired Glucose Tolerance and Diabetes Mellitus, 27 DIABETES RES. AND CLIN. PRACT. 181-88 (1995) ("Scragg"). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. NATURE OF THE CLAIMED INVENTION Appellants' invention is directed to a method of treating hyperglycemia in a human with 25-hydroxyvitamin D3 ( calcifediol). Abstr. REPRESENTATIVE CLAIM Claim 1 is illustrative of the claims on appeal and recites: 1. A method of treating a human in need of maintaining blood plasma glucose at a level between 4 mmol/L and 7 mmol/L comprising the steps of: identifying the human in need of maintaining blood plasma glucose at a level between 4 mmol/L and 7 mmol/L; 2 Appeal2018-004569 Application 13/840,825 administering 25-hydroxyvitamin D3 (25-0H D3) and vitamin D3 to the human in an amount sufficient to maintain blood plasma glucose at a level between 4 mmol/L and 7 mm o 1/L. App. Br. 34. Depending from claim 1, claim 9 recites a ratio of vitamin D3 to 25-0H D3 of from about 6:1 to 1:6. See also, claim 19. Claims 10 and 11, respectively, recite periodic dosages of 7 to 350 and 30 to 1500 micrograms each of the two compounds. See also, claims 20, 21. ISSUES AND ANALYSES We are persuaded by, and expressly adopt, the Examiner's findings, reasoning, and conclusion that Appellants' claims are prima facie obvious over the combined cited prior art. We address the arguments raised by Appellants below. A. Rejection of claims 1, 7, 8, 12, 13, 15-18, 22, 23, and 25 under 35 U.S.C. § 103(a) Issue Appellants argue these claims together. App. Br. 9. Appellants contend that the Examiner erred because the cited references provide no basis for a person of ordinary skill in the art "to assume, or even conjecture, that administration of the claimed combination of 25-hydroxyvitamin D3 3 Appeal2018-004569 Application 13/840,825 (25-0H D3) and vitamin D3 would have any effect on bringing glucose levels to the claimed desirable level." App. Br. 14. Analysis The Examiner finds that Chung teaches combination of both 25- hydroxyvitamin D3 and vitamin D3 in a ratio as recited in Appellants' claims. Final Act. 4. The Examiner finds that Chung teaches the combination as a dietary supplement for consumption by humans and animals, and also teaches the food product prepared in packaged human food. Id. at 5 (citing Chung 5, Ex. 3). The Examiner finds that Krammer teaches the ratio of 25- hydroxyvitamin D3 and vitamin D3 in a ratio range from 1 :9 or 9: 1 which overlaps with Appellants' claimed ratios of 1: 6 or 6: 1, and a preferred range 1: 1. Final Act. 6. The Examiner finds that Krammer teaches compositions comprising 25-hydroxycholecalciferol (25-0H D3) for preventing and treating joint diseases in pets. Id. ( citing Krammer ,r,r 2-9, 11, 12). The Examiner finds that Pittas teaches that a daily intake of greater than 800 IU vitamin D and greater than 1200 mg calcium was associated with a 33% lower risk of type 2 diabetes as compared with a daily intake of less than 400 IU and 600 mg calcium and vitamin D, respectively. Final Act. 7 ( citing Pittas ,r 20). The Examiner finds that Pittas teaches an inverse association between calcium and vitamin D status, as measured by serum 25-hydroxyvitamin D3 concentration and calcium intake, respectively, and prevalence of type 2 diabetes, namely that low levels are associated with a high prevalence of type 2 diabetes. Id. The Examiner notes that Pittas teaches that consumption of dairy products, a rich source of both calcium 4 Appeal2018-004569 Application 13/840,825 and vitamin D, has also been associated with decreased risk of type 2 diabetes. Id. The Examiner finds that Bishop teaches administration of 25- hydroxyvitamin D3 for maintaining restoring and maintaining blood concentration of 25-hydroxyvitamin D3 at optimal levels. Final Act. 7. The Examiner concludes that it would have been obvious to a person of ordinary skill in the art to reduce or maintain the blood plasma glucose level of a patient by administering 25-hydroxyvitamin D3 and vitamin D3 sufficient to reduce or maintain blood plasma glucose level at a desired level. Final Act. 13. The Examiner also find that Pittas and Scragg teach that there is a relationship between 25-hydroxyvitamin D3 and the glycemic index, therefore, the Examiner reasons a skilled artisan would have had a reasonable expectation of success in a method of treating a human comprising administering 25-hydroxyvitamin D3 and vitamin D3 in an amount sufficient to reduce or maintain blood plasma glucose level between 4 mmol/L and 7 mmol/L, as recited in Appellants' claims. Id. Appellants argue that none of the cited references, individually or combined, relates to a method for controlling glucose level in blood. App. Br. 10. Appellants argue that Chung is directed to a fertility treatment for boars using 25-0H D3 and vitamin D3, and does not teach a method of maintaining a blood plasma glucose level in humans. Id. Appellants contend that Krammer is directed to methods of using of 25-0H D3, either alone or in combination with 25-0H D3, for use in pet food, particularly for large dogs, to prevent and treat joint diseases, such as osteochondrosis, degenerative arthritis or arthropathy. App. Br. 10-11. 5 Appeal2018-004569 Application 13/840,825 Appellants assert that the methods taught by Krammer are unrelated to controlling glucose levels in a human. Id. at 11. With respect to Bishop, Appellants argue that the reference is directed to methods of using a pharmaceutical composition comprising vitamin D3 and/or vitamin D2 to treat vitamin D deficiency, i.e., 25-hydroxy vitamin D insufficiency or deficiency. App. Br. 11. Appellants note that Bishop teaches that 25-hydroxy vitamin D3 is a pro-hormone, which is metabolized into the hormone 1, 25-dihydroxy vitamin D3. Id. Appellants contend that Bishop teaches that vitamin D hormones are required for normal bone formation and metabolism. Id. ( citing Bishop ,r,r 9, 11 ). Appellants assert that there is no teaching or suggestion in Bishop that 25-hydroxy vitamin D3 should be administered together with vitamin D3 and/or D2 for controlling blood glucose levels. Id. at 11-12. To the contrary, Appellants argue, Bishop teaches against the use of 25-0H D3 as an immediately available form. Id. at 12 (citing Bishop col. 11, 11. 27-31). Appellants argue that Pittas is directed to studies in which participants (1) have a normal fasting glucose level of less than 5.6 mmol/L; or (2) have glucose levels of between 5.6 to 6.9 mmol/L. App. Br. 12 (citing Pittas 980). Appellants contrast this study to Appellants' claims, the claimed goal of which is to reduce glucose levels and bring them to between 4 mmol/L and 7 mmol/L. Id. Appellants assert that none of the test subjects of Pittas are within this group, because they are already able to maintain their blood glucose levels between 5.6 to 6.9 mmol/L. Id. at 12-13. Appellants argue that a skilled artisan would not have consulted Pittas to determine how to maintain a claimed glucose level, because the test subjects of Pittas could already do this without outside intervention. Id. at 13. 6 Appeal2018-004569 Application 13/840,825 With respect to Scragg, Appellants argue that the reference provides no evidence with which to form a basis for treatment, because Scragg teaches that its study cannot determine whether levels of hydroxyvitamin D3 can be a cause of, or have any effect on, the underlying disease. App. Br. 13 ( citing Scragg 186). Appellants also note that Scragg teaches that further studies are required to make that determination. Id. ( citing Scragg 187). Appellants contend that the Examiner has not explained how a combination of the cited references would have rendered obvious a first step of identifying a human in need of maintaining blood plasma glucose at a level between 4 mmol/L and 7 mmol/L because a combination of the references is not related to controlling blood glucose levels. App. Br. 14. Finally, Appellants argue that their invention has exhibited unexpected results. App. Br. 14. Appellants point to the Examiner's finding that a high level of 25-0H D3 is indicative of disease. App. Br. 14--15 (quoting Final Act. 15). Therefore, Appellants argue, the claims on appeal Appellants' claims are patentable, because the administration of 25-0H D3 is counterintuitive because, according to the Examiner, a high level of 25-0H D3 is indicative of disease. Id. at 15. Appellants' further point out that the Examiner's observations with respect to both high and low levels of 25-0H D3 are not material to the claims on appeal, which are instead directed to the maintenance of blood glucose levels: there are no claims reciting the levels of 25-0H D3. Id. We are not persuaded by Appellants' arguments. Scragg teaches a study designed: [T]o determine whether serum concentrations of 25- hydroxyvitamin D3 are altered in people with newly diagnosed diabetes mellitus and impaired glucose tolerance (IGT). Serum 7 Appeal2018-004569 Application 13/840,825 25-hydroxyvitamin D3 concentration was significantly lower in newly detected cases with diabetes and IGT (n = 238) compared with controls individually matched by sex, age [ ... ], ethnicity, and date of interview [ .... ] Scragg Abstr. Scragg summarizes the results of its study thus: The main issue is whether low levels of 25-hydroxyvitamin D3 are causal of IGT and diabetes or a consequence of the disease process. Clearly, our paper cannot decide on the issue of causation since the data are cross-sectional. Intervention or prospective studies are required to decide on this issue. However, our results, when combined with previous reports, do support a possible causal role from decreased vitamin D for the following reasons. Firstly, the IGT cases in our study represent an early stage in the disease process which is reversible, and therefore their decreased vitamin D levels seem unlikely to be a consequence of the disease process. Secondly, evidence from other human studies suggests that neither hyperglycaemia nor treatment with insulin affects serum 25-hydroxyvitamin D levels in the short term .... Thirdly, a growing body of both human and animal experimental work has shown that vitamin D deficiency decreases insulin secretion, while vitamin D supplementation improves it. Id. at 186 ( emphasis added, internal citations omitted). We agree with the Examiner that Scragg thus teaches that decreased levels of 25- hydroxyvitamin D3 are coincident with diabetes and IGT, and suggests that their evidence supports the contention that there may be a causal link between the decreased level of 25-hydroxyvitamin D3 and diabetes and/or IGT. Scragg also directly suggests that intervention studies, i.e., the administration of 25-hydroxyvitamin D3 ( or its metabolic precursor vitamin D3) could ameliorate diabetes or IGT. Pittas teaches that: 8 Appeal2018-004569 Application 13/840,825 [W]e found that daily supplementation with 500 mg calcium citrate and 700 IU vitamin D3 for 3 years prevented increases in plasma glucose and insulin resistance in the subgroup of participants with IFG [impaired fasting glucose] at baseline but had no apparent effect among those with NFG [ normal fasting glucose]. Pittas 983. Pittas thus similarly teaches that administration of, inter alia, vitamin D3 prevented increases in plasma glucose and insulin resistance in patients with IFG [impaired fasting glucose]. We acknowledge that Pittas states these individuals did not suffer directly from diabetes (see Pittas Abstr.), nevertheless, administration of vitamin D3 to IFG patients prevented increases in blood glucose compared to control groups, which reported blood glucose levels of greater than or equal to 7 mmol/L. Id. This exceeds the blood glucose levels recited as acceptable in the claims, and, furthermore, the claims are not limited to patients with diabetes, but are more broadly directed to those "in need of maintaining blood plasma glucose at a level between 4 mmol/L and 7 mmol/L. " We find that the IFG patients of Pittas fall within the scope of this limitation. The test of obviousness is what the combined teachings of the references would have suggested to those of ordinary skill in the art. In re Keller, 642 F.2d 413,425 (C.C.P.A. 1981). In the appeal presently before us, the combination of Scragg and Pittas suggests a causative link between lowered levels of 25-hydroxyvitamin D3 and elevated blood glucose levels and insulin resistance. Furthermore, we agree with the Examiner that the combined references also suggest that administration of a combination of 25-hydroxyvitamin D3 and vitamin D3 could lower blood glucose and decrease insulin resistance in patients in need thereof. We conclude that, 9 Appeal2018-004569 Application 13/840,825 upon comprehending the teachings of the cited prior art, a person of ordinary skill in the art would understand that administration of a combination of 25- hydroxyvitamin D3 and vitamin D3 to a person in need could reasonably be expected to be successful in maintaining blood glucose levels at a level between 4 mmol/L and 7 mmol/L. Appellants contend that their invention has exhibited unexpected results because the Examiner finds that a high level of 25-hydroxyvitamin D3 is indicative of disease. See App. Br. 14. However, Scragg teaches that: "We have shown that raised serum levels of 25-hydroxyvitamin D3 are associated with a significantly decreased risk of IGT and NIDDM [ non- insulin-dependent diabetes mellitus] after adjusting for possible confounders such as BMI [body mass index], leisure physical activity and hypertension." Scragg 186 ( emphasis added). We find that this teaching, although contradicting the Examiner's unsupported finding (see Final Act. 15), is entirely consonant with the other teachings of the art and that Appellants' argument of unexpected results are, consequently, without merit. We consequently affirm the Examiner's rejection of claims 1, 7, 8, 12, 13, 15-18, 22, 23, and 25. B. Rejection of claims 9 and 19 under 35 U.S.C. § 103(a) Appellants argue these claims separately. App. Br. 15. In addition to relying upon their arguments presented supra, Appellants argue that the combined references neither teach nor suggest the limitation reciting: "wherein the ratio of Vitamin D3 to 25-0H D3 is from about 6:1 to 1:6." Id. at 17. Appellants contend that, contrary to the Examiner's findings, Chung 10 Appeal2018-004569 Application 13/840,825 does not teach or suggest the claimed ratio of 25-0H D3 and Vitamin D3 as a composition for human consumption. Id. We are not persuaded. Chung expressly teaches that: "In the framework of the invention, with animals is meant animals, including mammals, examples of which include humans." Chung 1. Example 3 of Chung teaches a premix for boar food with a 1: 1 ratio of vitamin D3 to 25- 0H D3. Spec. 5. Although Chung does not expressly teach a composition within the claimed range of vitamin D3:25-0H D3 ratios, Chung teaches that its compositions can also be administered to humans. See id. We consequently affirm the Examiner's rejection of claims 9 and 19. DECISION The Examiner's rejection of claims 1, 7-13, 15-23, and 25 under 35 U.S.C. § 103(a) 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)(l). See 37 C.F.R. § 1.136(a)(l)(iv) (2010). AFFIRMED 11 Copy with citationCopy as parenthetical citation