Ex Parte Pollentier et alDownload PDFPatent Trial and Appeal BoardAug 30, 201311039991 (P.T.A.B. Aug. 30, 2013) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE ________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ________________ Ex parte STEPHANE POLLENTIER, ANDREAS RASCHIG, JUERGEN REESS, OLE GRAFF, BIRGIT OHRT MIKKELSEN, and MORTEN PRISKORN ________________ Appeal 2011-009669 Application 11/039,991 Technology Center 1600 ________________ Before FRANCISCO C. PRATS, ERICA A. FRANKLIN, and JOHN G. NEW, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL1 1 Appellants identify NEUROSEARCH A/S of Ballerup, Denmark as the real party in interest. (App. Br. 1.) Appeal 2011-009669 Application 11/039,991 2 SUMMARY Appellants file this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 1, 12, 27, 30, 32, and 39-60. Specifically, claims 1, 12, 27, 30, 32, 39-50 and 55-60 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over Scheel-Krüger et al. (WO 97/30997, August 28, 1997) (“Scheel-Krüger”). Claims 51-54 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Scheel-Krüger and George A. Bray, Drug treatment of obesity, 55 AM. J. CLIN. NUTR. 538S-544S (1992) (“Bray”). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. NATURE OF THE CLAIMED INVENTION Appellants’ invention is directed “to the use of a monoamine neurotransmitter re-uptake inhibitor comprising a 2,3-disubstituted tropane moiety, or a tautomer, a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof for a medicament for the for the [sic] sustained reduction of body weight.” Abstract. GROUPING OF CLAIMS Appellants argue that the Examiner erred for essentially the same reasons with respect to claims 1, 12, and 27, 39, and 41-49. App. Br. 9, 46, 47, 48, 49; see also 37 C.F.R. § 41.37(c)(1)(vii) (“A statement which merely points out what a claim recites will not be considered an argument for separate patentability of the claim”). We therefore select claim 1 as App App repre fall w App 43, 4 recit eal 2011-0 lication 11 sentative ith claim Claim 1 1. comprisi ad of body ab 1A or said dail compoun . Br. 53. Appellan 5, 46, 47. es: 32 compoun thereof i 1.0 mg d 09669 /039,991 of these cl 1. See 37 recites: A metho ng: ministerin weight a d out 0.1 m a pharm y dose is d. ts select c We select . The m d of form s administ aily based aims. Cla C.F.R. § 4 d for a su g to a hum aily dose o g to about aceutically calculated laims 30, independ ethod acc ula 1A or ered in a on the fre 3 ims 12, an 1.37(c)(1) stained re an in nee f a compo 2.0 mg o acceptab based on 32 and 40 ent claim 3 ording to a pharma weight of e base for d 27, 39, a (vii). duction o d of susta sition com f a compo le salt th the free ba as a single 2 as repre claim 1 ceutically about 0.12 m of said c nd 41-49 s f body w ined redu prising: und of for ereof; wh se form o group. A sentative. , wherein acceptable 5 mg to a ompound tand or eight ction mula erein f the pp. Br. Claim 32 the salt bout . App App recit App selec App recit eal 2011-0 lication 11 Appellan es: 50. Th to said h . Br. 56. Appellan t independ 56 comprisi or reductio comprisi or said dail compoun . Br. 57-58 Appellan es: 58 formula in the fo 09669 /039,991 ts select c e method uman dail ts select c ent claim . A meth ng: ally admi n of bod ng: 0.1 mg a pharm y dose is d. . ts select c . The met 1A or sai rm of a cit laim 50 as of claim 1 y for at lea laims 55-6 56 as repr od for a s nistering y weight to 2.0 mg aceutically calculated laim 58 as hod of cla d pharmac ric acid sa 4 a single g , wherein st 28 days 0 as a sin esentative ustained r to a huma a daily of a com acceptab based on a single g im 56, wh eutically lt of said c roup. App said dose . gle group. . Claim 56 eduction o n in nee dose of pound of f le salt th the free ba roup. App erein said acceptable ompound. . Br. 44. is adminis App. Br. 4 recites: f body w d of susta a compos ormula lA ereof, wh se form o . Br. 45. compoun salt there Claim 50 tered 4. We eight ined ition erein f the Claim 58 d of of is Appeal 2011-009669 Application 11/039,991 5 App. Br. 58. Appellants argue that the Examiner erred for substantially the same reasons with respect to claims 51-54. App. Br. 49-51. We select claim 51 as representative. Claim 51 recites: 51. The method of claim 1, wherein said daily dose is administered to said human every morning for 28 days. App. Br. 57. ISSUES AND ANALYSES A. Claim 1 Issue 1 Appellants argue that the Examiner erred in finding that it would have been obvious to select the claimed compound from amongst the compounds taught by Scheel-Krüger. App. Br. 22. We therefore address the issue of whether the Examiner so erred. Analysis Appellants argue that, because the field of monoamine reuptake inhibitors is broad, and encompasses a large number of compounds of heterogenous structure, the Examiner erred by finding it would be obvious to select the claimed compound in the absence of clear directions or reasons for making such selection. App. Br. 11-12, 21 (citing Padwal Decl.2 2, 12- 14). Appellants argue that, in focusing only on the Scheel-Krüger reference, and in ignoring all of the other art of record, as well as the 2 Second Declaration of Raj Padwal, submitted May 11, 2009. Appeal 2011-009669 Application 11/039,991 6 comments on that prior art by Dr. Raj Padwal, the Examiner is improperly concluding that there is a “very short list of preferred compounds.” App. Br. 22 (citing Padwal Dec.3 3, ¶¶ 11, 16). Furthermore, argue Appellants, even if one skilled in the art were to focus solely on Scheel-Krüger and ignore all of the other prior art, the invention recited in the claims on appeal involves the use of one single specific compound, whereas Scheel-Krüger discloses numerous specific compounds. App. Br. 22. Appellants contend that the Scheel-Krüger disclosure provides no nexus between 2-ethoxymethyl-3-(3,4 dichlorophenyl)-tropane (“tesofensine”) and any treatment of obesity, much less between that specific compound and “sustained reduction of body weight” by the method of use specified in Appellants' claim 1. Appellants argue further that, even if there is in fact a list of preferred compounds in the prior art for treating obesity, tesofensine is not on that list. App. Br. 23. Appellants point to the testimony of Dr. Padwal, who opined: I have also been asked to comment on what compounds I would 'short-list' to be lead candidates for sustained reduction of body weight in early 2004, based upon all of the literature and patents discussed in this Declaration, as well as my two previous Declarations …. When considering drug classes that have a similar mechanism of action to that of sibutramine (monoamine reuptake inhibition), one must understand that numerous therapeutic classes are thought to act in this manner, including selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, tricyclic antidepressants and tropane derivatives. Additionally, I would consider the drugs listed in Section C (zonisamide, bupropion and topiramate) or 3 Third Declaration of Raj Padwal, submitted Feb. 28, 2010. Appeal 2011-009669 Application 11/039,991 7 structurally related drugs as lead candidates because they already were in use as anti[-]epileptics and, therefore, safety profiles were less of an unknown. Third, of the drugs listed in Section D, I would consider the endocanabinoid receptor antagonists as the most promising in early 2004. Padwal Decl. 3, ¶ 16. Appellants also argue that the Examiner incorrectly selected tesofensine as the “lead compound” from among the compounds taught by Scheel-Krüger. App. Br. 25. Appellants contend that, in the pharmaceutical field, a prima facie case of obviousness generally begins with identification of a “lead” compound. App. Br. 24 (citing Eisai Co. Ltd. v. Dr. Reddy's Laboratories, Ltd., 533 F.3d 1353, 1359 (Fed. Cir. 2008) and Takeda Chemical Industries, Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007)). Appellants argue that the Examiner is impermissibly focusing on tesofensine as the “lead compound” (based on hindsight) while ignoring what Appellants allege is much more relevant prior art, as well as the Declarations of Appellants’ experts, which have interpreted all of the prior art (and not just Scheel-Krüger). App. Br. 25. Appellants insist that the Examiner must consider all of the relevant teachings of the prior art and select a lead compound without the use of hindsight. Id. Appellants contend that, based upon their experts review of the prior art, the most suitable “lead” compound at the time the invention was made would have been sibutramine, which has been approved for long term treatment of obesity. Id. (citing Diana Rucker, Raj Padwal, Stephanie K Li, Cintia Curioni and David C W Lau, Long term pharmacotherapy for obesity and overweight: updated meta-analysis, 335 BMJ, 1194-99 (2007) Appeal 2011-009669 Application 11/039,991 8 (Exhibit 3C); Padwal Decl. 3, p. 7, l. 5-7; and Padwal Decl.4 1, p. 3, last paragraph). The Examiner responds that Scheel-Krüger teaches that Appellants’ preferred tropane compounds are selected from one of thirteen compounds. Ans. 8 (citing Scheel-Krüger, Abstract). The Examiner finds that Scheel- Krüger teaches that these monoamine neurotransmitter reuptake inhibitor compounds are useful for the treatment of disorders responsive to the inhibition of monoamine neurotransmitter reuptake, such as “Parkinson's disease, depression, obsessive compulsive disorders, panic disorders, dementia, memory deficits, attention deficit hyperactivity disorder, obesity, anxiety, eating disorders and drug addiction or misuse.” Ans. 8-9 (citing Scheel-Krüger, p. 1). The Examiner also finds that a lead compound analysis, as proposed by Appellants, is unnecessary, because Scheel-Krüger provides sufficient motivation to bypass such an analysis. Ans. 9. The Examiner finds that Scheel-Krüger teaches that the disclosed tropane compounds have the ability to inhibit monoamine reuptake, and that this property is particularly useful in the treatment of obesity and eating disorders, among other diseases not related to the instant application. Id. We agree with the Examiner. As an initial matter, Appellants’ “lead compound” analysis is inapposite. Such an analysis is employed, as it is in both Takeda and Eisai, when determining whether it would have been obvious to modify a compound to produce a related compound as a means of potentially enhancing its properties. See Takeda, 492 F.3d at 1357. In 4 First Declaration of Raj Padwal, submitted May 11, 2009. Appeal 2011-009669 Application 11/039,991 9 the instant appeal, the Examiner finds, and Appellants do not dispute, that Scheel-Krüger explicitly teaches the same compound recited in claim 1. Consequently, a “lead compound” analysis is neither necessary nor appropriate. With respect to Appellants’ arguments that the Examiner erred by not considering the entire field of monoamine reuptake inhibitors when determining whether it would have been obvious to select tesofensine as a compound with anti-obesity properties; we are not persuaded. The Examiner finds that tesofensine is one of a limited number (thirteen) of novel tropane derivatives for the treatment of disorders responsive to the inhibition of monoamine neurotransmitter re-uptake including, inter alia, obesity. Scheel-Krüger, p.1; see Ans. 9. Given the restricted number of tropane derivatives, including tesofensine, taught by Scheel-Krüger, and its teachings that such compounds are effective in the treatment of disorders responsive to monoamine reuptake inhibitors, we agree with the Examiner that it would have been obvious to select tesofensine as a compound for the treatment of obesity. See Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (“Disclos[ure of] a multitude of effective combinations does not render any particular formulation less obvious.”). With respect to Appellants’ arguments concerning the large breadth of the prior art’s scope, such extensive prior art does not preclude a finding of obviousness if the prior art expressly teaches the claimed compound. See In re Susi, 440 F.2d 442, 445 (C.C.P.A. 1971) (obviousness rejection affirmed where the disclosure of the prior art was “huge, but it undeniably include[d] at least some of the compounds recited in appellant’s generic Appeal 2011-009669 Application 11/039,991 10 claims and it is of a class of chemicals to be used for the same purpose as appellant's additives”). We therefore conclude that the Examiner did not err in finding claim 1 obvious over the prior art reference. Issue 2 Appellants argue that the Examiner erred in finding that an artisan of ordinary skill would have had a reasonable expectation that the present invention would work as recited in claim 1. App. Br. 32. We therefore address the issue of whether the Examiner so erred. Analysis Appellants argue that the unpredictability of monoamine reuptake inhibitors preclude the possibility that a person of ordinary skill would have had a reasonable likelihood of success in treating obesity. App. Br. 32. Appellants point to the Declaration of Dr. Padwal, who opined: Monoamine reuptake inhibitors are not a homogeneous class of drugs, but rather represent a loose collection of different drugs that have substantially different chemical structures and non-obesity treatment indications. App. Br. 11 (quoting Padwal Decl. p.2, ll. 12-14). Appellants also adduce the testimony of Dr. Arne Astrup,5 who opined: I have reviewed the disclosure of Scheel-Krüger and considered the state of the art in early 2004 in view of the obtained results and meta-analysis regarding tesofensine as discussed above. Scheel-Krüger discloses a host of compounds regarding many possible diseases and conditions. However, the 5 Declaration of Arne Astrup, submitted June 19, 2009. Appeal 2011-009669 Application 11/039,991 11 state of the art is so unpredictable that an individual assessment of any particular compound would be needed. In other words, despite the comprehensive listing of treating diseases or conditions such as dementia, panic disorders, cocaine abuse, and Parkinson's disease, there is no way to reasonably predict which particular compound disclosed in Scheel-Krüger would lead to a particular property, including a sustained reduction of body weight. This is because any change in the chemical structure of a compound, wherein the compound is a gastrointestinal lipase inhibitor (i.e., orlistat), cannabinoid receptor antagonist (i.e., rimonabant) or a neurotransmitter reuptake inhibitor (i.e., sibutramine), would give unpredictable results. There is no method to reasonably predict the extent to which the drug will reduce weight (or have some other value or side effect) prior to clinical testing in animal and human models. App. Br. 13 (quoting Astrup Decl., pp. 7-8). Appellants argue further that Scheel-Krüger teaches that tesofensine and the other disclosed tropane derivatives may be useful in the treatment of obesity, but also a number of other possibly contradictory disorders, or combination of disorders. App. Br. 33. Appellants argue that the Examiner is therefore impermissibly using hindsight to arrive at the combination of using the claimed compound to treat obesity. Id. The Examiner responds that, at the time Appellants’ invention was made, it was well-known in the art that monoamine neurotransmitter re- uptake inhibitors are useful for treating diseases such as obesity and over- eating. Ans. 10 (citing well known anti-obesity drug, sibutramine). The Examiner finds that the compounds disclosed by Scheel-Krüger are taught to have the same biological property of inhibiting monoamine re-uptake as other well-known anti-obesity agents. Id. The Examiner finds that Scheel- Appeal 2011-009669 Application 11/039,991 12 Krüger explicitly teaches that the disclosed tropane compounds are useful for treating obesity and over-eating. Id. (citing Scheel-Krüger, p. 1). The Examiner also finds that the prior art explicitly teaches the elected compound and the genus of compounds for the same claimed method. Ans. 10. The Examiner finds that, although the prior art teaches the treatment of several diseases, the diseases taught are linked by one mechanism of action which is disclosed by the prior art. Id. The Examiner therefore finds that there would have been sufficient motivation for any person to select the instantly claimed tropane compound with a reasonable expectation for success in treating obesity. Ans. 10-11. We agree with the Examiner. “The fact that some … compounds function more effectively, and that the exact magnitude of the increased … activity might not be predictable, does not preclude a conclusion of obviousness. Only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness.” In re Longi, 759 F.2d 887, 897 (Fed. Cir. 1985). We find that Scheel-Krüger teaches the use of the claimed compound, an effective monoamine reuptake inhibitor, for the treatment of disorders that are treatable by the administration of monoamine reuptake inhibitors. Scheel-Krüger, p.1; see Ans. 11. We therefore conclude that the Examiner did not err in finding that a person of ordinary skill in the contemporary art would have had a reasonable expectation of success in using the claimed invention to treat obesity and find that the Examiner did not impermissibly employ hindsight. Appeal 2011-009669 Application 11/039,991 13 Issue 3 Appellants next argue that Scheel-Krüger teaches away from the limitation of claim 1 reciting “a daily dose of a composition comprising about 0.1 mg to about 2.0 mg.” App. Br. 36. We therefore address the issue of whether the Examiner so erred. Analysis Appellants contend that Scheel-Krüger teaches a broad range of suggested dosages of 0.1-500 mg/day, with a preferred dosage range of 10- 70 mg/day, whereas their claimed invention teaches a broad and preferred dosage range of 0.1-2.0 (approximately) mg/day. App. Br. 35. Appellants argue that the range recited in Appellants’ claim 1 falls at the very bottom of the broad dosage range recited in Scheel-Krüger, and emphasize that it falls completely below the preferred dosage range taught by Scheel-Krüger. Id. (citing Scheel-Krüger, p. 20, l. 5). Appellants argue that a person of ordinary skill in the art would not be motivated to arrive at the daily dose comprising about 0.1 mg to about 2.0 mg of the compound, as recited in the limitation, from a teaching of a preferred dose of 10-70 mgs daily. App. Br. 36. Appellants contend that, because the upper end of the claimed range (2.0 mg) is only 20% of the lower end of the preferred range disclosed in Scheel-Krüger (10 mg), the prior art therefore teaches away the dosage range recited in claim 1. Id. at 36-37 (citing Ex parte Whalen, 89 USPQ2d 1078, 1083 (B.P.A.I. 2008). The Examiner responds that it is not inventive to discover the optimum or workable ranges by routine experimentation when the general conditions of a claim are disclosed in the prior art. Ans. 11 (citing In re Appeal 2011-009669 Application 11/039,991 14 Aller, 220 F.2d 454, 456 (C.C.P.A. 1955); MPEP 2144.05(11)). The Examiner finds that the determination of an optimum dosage regimen between about 0.1 to 2.0 mg or about 0.125 to 1 mg per day with the presently claimed active agent would have been a matter well within the knowledge and ability of one of ordinary skill in the art and such a determination could have been made in accordance with a variety of factors, including such factors as the age, weight, sex, diet, and medical condition of the patient, severity of the disease, the route of administration, pharmacological considerations (i.e., the activity, efficacy, pharmacokinetics and toxicology profiles of the particular compound employed), whether a drug delivery system is utilized and whether the compound is administered a part of a drug combination. Ans. 11. The Examiner finds that, because it was well-known in the contemporary art and also well within the ability of a skilled artisan to modify or perform routine optimization of a drug dosage for administration to a specific patient population, one of ordinary skill would have been motivated to experiment with dosage ranges by a reasonable expectation in providing a weight loss benefit. Id. The Examiner also finds that, in cases where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. Ans. 11-12 (citing MPEP 2144.05). We agree with the Examiner. As an initial matter, we find that Scheel-Krüger does not teach away from the claimed invention. A reference may be said to teach away when “a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that Appeal 2011-009669 Application 11/039,991 15 was taken by the applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). In the instant appeal, the broad range of dosages taught by Scheel- Krüger directly overlaps the dosage range recited in claim 1. Appellants do not point to, nor can we find, any teaching of Scheel-Krüger that would discourage or divert an artisan of ordinary skill from arriving at the dosage range recited in claim 1. Furthermore, “[i]n cases involving overlapping ranges, …even a slight overlap in range establishes a prima facie case of obviousness.” In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003); see also In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997); In re Woodruff, 919 F.2d 1575, 1578 (C.C.P.A. 1990); In re Malagari, 499 F.2d 1297, 1303 (C.C.P.A. 1974); see also In re Antonie, 559 F.2d 618, 620 (C.C.P.A. 1977) (“[T]he discovery of an optimum value of a variable in a known process is normally obvious”). In the instant appeal, the broad range of dosages taught by Scheel-Krüger completely encompasses the range of dosages recited in claim 1. We therefore conclude that the Examiner did not err in finding that it would have been obvious to one of ordinary skill in the art, in view of the teachings and suggestions of Scheel-Krüger, to arrive at the dosages recited in claim 1. Issue 4 Appellants argue that secondary considerations of nonobviousness, viz., the experimental results cited in the Astrup Declaration, are unexpected and rebut the Examiner’s prima facie case of obviousness. App. Br. 37. We therefore address the issue of whether the allegedly unexpected results are sufficient to rebut the Examiner’s findings. Appeal 2011-009669 Application 11/039,991 16 Analysis Appellants argue that, in his Declaration, Dr. Astrup opines that Appellants’ claimed invention achieved unexpected results. App. Br. 38. Dr. Astrup testified that, in clinical studies, the weight loss produced by tesofensine was at least twice that of expectations: tesofensine at 0.25 mg, 0.5 mg and 1.0 mg and diet induced weight loss of 4.5%, 9.2% and 10.6% greater than diet and placebo (p < 0.000l) for a period of 24 weeks. Id. (citing Astrup Decl. pp. 4-5). Dr. Astrup avers that these results were seen either over a 24 week period (6 months) or 58 weeks (for dosage of 0.5 mg of tesofensine versus placebo). App. Br. 38 (citing Astrup Decl. pp. 5-6). Dr. Astrup states that the weight loss produced by tesofensine for six months was very effective and surprisingly better than that of orlistat, sibutramine or rimonabant, the currently approved drugs on the market. App. Br. 38 (citing Astrup Decl. pp. 6-7). Appellants also argue that the Examiner, with respect to Dr. Padwal’s Declaration, accepted only Dr. Padwal’s statements that acknowledge that monoamine reuptake inhibitors should be considered as potential anti- obesity agents and ignores his conclusions that the results of the claimed invention are unexpected. App. Br. 39, 43 (quoting Padwal Decl. 3, ¶ 19). Appellants contend, therefore, that since both of their experts opine that Appellants’ claimed invention has provided significant unexpected results, and the Examiner’s finding of a prima facie case of obviousness is effectively rebutted. App. Br. 39, 43. The Examiner responds that, although the record may establish evidence of secondary considerations which are indicia of nonobviousness, the record also establishes such a strong prima facie case of obviousness Appeal 2011-009669 Application 11/039,991 17 that the objective evidence of nonobviousness is not sufficient to outweigh the evidence of obviousness. Ans. 12 (citing Newell Cos. v. Kenney Mfg. Co., 864 F.2d at 769. The Examiner finds that Scheel-Krüger would motivate any ordinary person to optimize the dosage of tesofensine being administered as well as teaches a dosage range that overlaps with dosages currently being claimed. Ans. 12. The Examiner finds that, if an ordinary person arrived at a dose of 0.5 or 1.0 mgs, the resulting composition would have been a product of ordinary skill and common sense, as would the benefits stemming therefrom. Id. We are not persuaded by Appellants’ arguments that the effectiveness of tesofensine in the treatment of obesity is sufficient to overcome the Examiner’s prima facie case of obviousness that we have related supra. The teachings of Scheel-Krüger would lead an artisan of ordinary skill to employ the disclosed compound in the treatment of obesity. We acknowledge the apparent expertise of Appellants’ experts and accept their statements to the effect that tesofensine is effective in the treatment of obesity. However, the treatment of obesity by Appellants’ claimed compound is what is taught or suggested by Scheel-Krüger, because it was then well-known in the art that monoamine reuptake inhibitors, of which the claimed composition is one, may be effective in the treatment of obesity. See Scheel-Krüger, p. 1. Moreover, although tesofensine demonstrates superior efficacy in the treatment of obesity, that secondary consideration is not, in itself, sufficient to overcome the strong prima facie case of obviousness established by the Examiner. See Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1372 (Fed. Cir. 2007) (“[W]e hold that even if Pfizer showed that [the claimed compound] exhibits unexpectedly superior results, Appeal 2011-009669 Application 11/039,991 18 this secondary consideration does not overcome the strong showing of obviousness in this case. Although secondary considerations must be taken into account, they do not necessarily control the obviousness conclusion”); see also Newell Cos., Inc. v. Kenney Mfg. Co., 864 F.2d at 768. We therefore conclude that the Examiner did not err in finding that the secondary considerations of nonobviousness did not overcome the Examiner’s prima facie evidence of obviousness. B. Claim 32 Issue Appellants argue that the narrower dosage range of about 0.125 to about 1.0 mg recited in claim 32 is outside the preferred dose mentioned in Scheel-Krüger and that the Examiner erred in finding it to be obvious over Scheel-Krüger. App. Br. 43-44. Analysis We have related supra how the range of dosages taught by Scheel- Krüger entirely overlaps Appellants claimed range of dosages. Those findings apply equally to claim 32, and we affirm the Examiner’s findings. C. Claim 50 Issue Appellants argue that the Examiner erred in finding that the cited prior art reference teaches or suggests the limitation of claim 50 reciting “The method of claim 1, wherein said dose is administered to said human Appeal 2011-009669 Application 11/039,991 19 daily for at least 28 days.” App. Br. 44, 49. We therefore address the issue of whether the Examiner so erred. Analysis Appellants argue that the experimental results reported by Dr. Astrup demonstrate that when administration occurs daily for 28 days or longer, significant and unexpected sustained reduction of body weight can be obtained. App. Br. 44. Appellants argue that these data further distinguishes claim 50 from the cited art. Id. We have related above our findings that the secondary considerations of nonobviousness are not sufficient to overcome the strong evidence of obviousness found by the Examiner. We therefore affirm the Examiner’s rejection of claim 50. D. Claim 55 Issue Appellants argue that the Examiner erred in finding that the cited prior art references teach or suggest the limitation of claim 56 reciting “orally administering to a human in need of sustained reduction of body weight a daily dose of a composition comprising: 0.1 mg to 2.0 mg of a compound of formula 1A.” App. Br. 44. We therefore address the question of whether the Examiner so erred. Analysis Appellants argue that, although the active ingredient of the present invention can be administered in a variety of different forms, oral Appeal 2011-009669 Application 11/039,991 20 administration is very convenient to patients and is the preferred mode of administration. App. Br. 44. Appellants argue further that the data regarding the effectiveness of tesofensine when orally administered is presented in the Declarations of Drs. Padwal and Astrup. App. Br. 44-45. Scheel-Krüger teaches that “[p]harmaceutical formulations include those suitable for oral, rectal, nasal, topical (including buccal and sub- lingual), vaginal or parenteral (including intramuscular, subcutaneous and intravenous) administration or in a form suitable for administration by inhalation or insufflation.” Scheel-Krüger 15 (emphasis added); see Final Rej. 7. We have related supra why we affirm the Examiner’s finding of obviousness with respect to the composition in claim 1 (which is the same as recited in claim 56), and we conclude the Examiner did not err in finding that Scheel-Krüger teaches or suggests the disputed limitation. E. Claim 58 Issue Appellants argue that the Examiner erred in finding that Scheel- Krüger discloses the limitation of claim 58 reciting “wherein said compound of formula 1A or said pharmaceutically acceptable salt thereof is in the form of a citric acid salt of said compound.” App. Br. 45. We address the issue of whether the Examiner so erred. Analysis Appellants argue that the active ingredient is in the form of the citric acid salt. App. Br. 45. Appellants contend that this salt is the preferred salt Appeal 2011-009669 Application 11/039,991 21 and is the salt form that was used in the clinical trials described by Dr. Astrup. See Exhibit 4E. The Examiner responds that Scheel-Krüger teaches the administration of the disclosed monoamine reuptake inhibitors (including Appellants’ claimed compound) as a citrate salt. Ans. 4. We agree with the Examiner. Scheel-Krüger teaches that: Examples of pharmaceutically acceptable addition salts include inorganic and organic acid addition salts such as … citrate, …. Such salts are formed by procedures well known in the art. Scheel-Krüger, 7; see Ans. 4. We therefore affirm the Examiner’s rejection. F. Claim 51 Issue Appellants argue that the Examiner erred in finding that claim 51 is obvious over the combination of Scheel-Krüger and Bray. App. Br. 49. We therefore address the issue of whether the Examiner so erred. Analysis Appellants argue that the Examiner erred because, in addition to the arguments advanced by Appellants with respect to claim 1, claim 51 is distinct from claim 1 in that administration is timed for the morning and for at least 28 days. App. Br. 49. The Examiner responds that Bray is directed to drug treatments for obesity. Ans. 6. The Examiner finds that Bray lists different types of agents known at the time to be useful for treating obesity. The Examiner finds that Bray teaches that clinical trials to measure the efficacy of such Appeal 2011-009669 Application 11/039,991 22 drugs last 3, 4, 8, or more weeks for the non-adrenergic agents and up to 52 weeks for the drugs affecting the serotonin neurotransmitter. Id. (citing Bray, 538S, 540S). The Examiner therefore finds that it would have been obvious to one of ordinary skill in the contemporary art to combine the teachings of Scheel-Krüger with Bray with a reasonable expectation for success in arriving at a method stimulating weight loss in a subject by administering the claimed tropane compound for at least 70 days. Id. We agree with the Examiner’s findings and adopt them as our own. Bray teaches or suggests the administering of monoamine re-uptake inhibitors for at least 70 days. See Bray, Fig. 2. We therefore affirm the Examiner’s rejection of claim 51. DECISION The Examiner’s rejection of claims 1, 12, 27, 30, 32, and 39-60 under 35 U.S.C. § 103(a) is affirmed. 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)(1). See 37 C.F.R. § 1.136(a)(1)(iv) (2011). AFFIRMED cdc Copy with citationCopy as parenthetical citation