13954834 (P.T.A.B. May. 25, 2018)

Ex Parte Song

Patent Trial and Appeal BoardMay 25, 2018

13954834 (P.T.A.B. May. 25, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/954,834 07/30/2013 127350 7590 05/30/2018 Steptoe & Johnson LLP 1330 Connecticut Avenue NW Washington, DC 20036 FIRST NAMED INVENTOR Jiasheng Song 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. 023849.US003 1155 EXAMINER BARSKY, JARED ART UNIT PAPER NUMBER 1628 NOTIFICATION DATE DELIVERY MODE 05/30/2018 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): hfox@steptoe.com rgreenfeld@steptoe.com ipdocketing@steptoe.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JIASHENG SONG 1 Appeal2017-005899 Application 13/954,834 Technology Center 1600 Before FRANCISCO C. PRATS, RYAN H. FLAX, and DAVID COTTA, Administrative Patent Judges. FLAX, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal under 35 U.S.C. Â§ 134(a) involving claims directed to a method of cancertreatment. 2 Claims 1, 2, 5-7, 10, 12- 14, and 16-18 are on appeal as rejected under 35 U.S.C. Â§ 103. We have jurisdiction under 35 U.S.C. Â§ 6(b ). We affirm-in-part. 1 "AhR Pharmaceuticals, Inc." is identified as the Real Party in Interest. Appeal Br. 2. 2 We have considered and herein refer to the Specification filed July 30, 2013 ("Spec."); Final Rejection mailed Aug. 27, 2015 ("Final Action"); Appeal Brief filed Mar. 25, 2016 ("Appeal Br."); Examiner's Answer mailed Jan. 3, 2017 ("Answer"); and Reply Brief filed Feb. 28, 2017 ("Reply Br."). Appeal2017-005899 Application 13/954,834 STATEMENT OF THE CASE The Specification states "[t]he endogenous ligand, or physiological ligand, or natural hormone, for the AhR was identified as 2-(1 'H-indole-3'- carbonyl)-thiazole-4-carboxylic acid methyl ester( ... ITE)," which is "derived from indole." Spec. ,r,r 4--5. Further, The presently disclosed invention relates to a method of cancer treatment using 2-(1 'H-indole-3'-carbonyl)-thiazole-4- carboxylic acid methyl ester ("ITE") or one of its structural analogs. More particularly, the present invention provides a method by administering a therapeutically effective amount of ITE or one of its structural analogs to treat cancer in a subject in need thereof including skin, colorectal, stomach, pancreatic, kidney, bladder, soft tissue, and cervical cancer. Independent claim 1 is representative and is reproduced below: 1. A method of cancer treatment comprising administering a therapeutically effective amount of 2-(l'H- indole-3 '-carbonyl)-thiazole-4-carboxylic acid methyl ester or one of its structural analogs at a dose of between 1 mg/kg and 200 mg/kg to a subject in need thereof, wherein the cancer is selected from a group consisting of skin, colorectal, stomach, pancreatic, kidney, bladder, soft tissue, and cervical cancer, wherein the said structural analog of 2-(l'H-indole-3'-carbonyl)- thiazole-4-carboxylic acid methyl ester has the formula: Structural Formula 4 2 Appeal2017-005899 Application 13/954,834 wherein: X and Y are independently selected from either O ( oxygen) or S (sulfur); R1, R2, R3, Ri, RN, Rs, and R7 are independently selected from hydrogen or halo (F, Cl, Br, or I); and R6 is: 0 11 -C-R10 wherein Rio is selected independently from -OCH3 (methoxy), -C2Hs (ethyl), -NHCH3 (methylamino), or-SCH3 (thiomethoxy). Appeal Br. (Claims App'x A-1). The following rejections are appealed: Claims 1, 2, 5-7, 10, 12-14, and 16-18 stand rejected under 35 U.S.C. Â§ I03(a) over DeLuca3 and Consumer Reports. 4 Answer 3. Claims 1, 2, 5-7, 10, 12-14, 17, and 18 stand rejected under 35 U.S.C. Â§ I03(a) over Ahn5 and Consumer Reports. Id. at 7. DISCUSSION Only those arguments made by Appellant in the Appeal Brief and properly presented in the Reply Brief have been considered in this Decision. Arguments not so presented in the Briefs are waived. See 37 C.F.R. Â§ 4I.37(c)(l)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474 3 US 7,419,992 B2 (issued Sept. 2, 2008) ("DeLuca"). 4 Philip Wilson, Fruit juice and medications don 't mix, Consumer Reports News (2008) ("Consumer Reports"). 5 WO 2009/070645 Al (pub. June 4, 2009) ("Ahn"). 3 Appeal2017-005899 Application 13/954,834 (BP AI 2010) (informative) ("Any bases for asserting error, whether factual or legal, that are not raised in the principal brief are waived."). "[T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting aprimafacie case ofunpatentability. 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). "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "[T]he analysis need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418. "In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid underÂ§ 103." Id. at 419. Where claimed subject matter has been rejected as obvious in view of a combination of prior art references, a proper analysis underÂ§ 103 requires, inter alia, consideration of two factors: (1) whether the prior art would have suggested to those of ordinary skill in the art that they should make the claimed composition or device, or carry out the claimed process; and (2) whether the prior art would also have revealed that in so making or carrying out, those of ordinary skill would have had a reasonable expectation of success. Both the suggestion and the reasonable expectation of success must be founded in the prior art, not in the applicant's disclosure. In re Vaeck, 947 F.2d 488,493 (Fed. Cir. 1991) (citation omitted). However, the "case law is clear that obviousness cannot be avoided simply 4 Appeal2017-005899 Application 13/954,834 by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007). Rejection over DeLuca The Examiner determined that the rejected claims would have been obvious over DeLuca and, regarding claim 7, combined with Consumer Reports. Final Action 2-11 and Answer 3-7, 14--34 ( collectively citing DeLuca3:9-10, 5:30-60, 5:67, 6:63---64, 10:3-24, 10:32-33, 11:30, 11:42- 55, 12:50; and citing Consumer Reports). Except as otherwise indicated below, we agree with and adopt the Examiner's findings of fact and discern no error in the Examiner's determinations. We address Appellant's arguments below. Appellant argues that DeLuca et al. in view of Consumer Reports News does not teach or suggest ITE or one of its structural analogs could predictably be used to treat skin, colorectal, stomach, pancreatic, kidney, bladder, soft tissue, or cervical cancer from the mere teaching of the genera "cancer" or "solid tumors." Appeal Br. 5. Appellant contends DeLuca merely teaches a genus of cancer treatment, which is not sufficient to teach the specific cancers claimed. Id. (citing In re Baird, 16 F.3d 380, 382 (Fed. Cir. 1994)). Also, Appellant cites the Song Declaration6 as evidencing that, contrary to DeLuca's affirmations at 11 :48-50, the skilled artisan would not have expected DeLuca's disclosed ITE dosage of 2-10 mg/kg to be efficacious to treat cancer. Id. at 6. Appellant argues that the Song Declaration is evidence that "[ t ]he teachings 6 Declaration of Inventor Jiasheng Song, Ph.D., Under 37 C.F.R. Â§ 1.132, dated May 13, 2015 ("Song Declaration"). 5 Appeal2017-005899 Application 13/954,834 of DeLuca are not enabled or operable for treating all cancers or even all solid tumors." Id. Appellant argues that the effect of AhR agonists on cancer is unpredictable and contends the art discloses that activating AhR with an agonist may promote tumor growth, initiation, and progression. Appeal Br. 6-7 (citing Dietrich). 7 Appellant contends the art teaches AhR agonists, e.g., TCDD, promote tumor formation/development and, specifically, cause pancreatic cancer, or accelerate metastasis. Id. at 7-8 ( citing Ray, 8 Knerr,9 Nyska, 10 and Ebos 11). Therefore, Appellant argues, "a practitioner in the art would not view ITE or its analogs as predictably being capable of treating all cancers, all solid tumors, or skin, colorectal, stomach, pancreatic, kidney, bladder, soft tissue, or cervical cancer." Id. at 7-8. Appellant argues that DeLuca does not resolve the unpredictability illustrated by the above-identified references, even with regard to treating 7 Kaina B. Dietrich, The Ary! Hydrocarbon Receptor (AhR) in the Regulation of Cell-Cell Contact and Tumor Growth, 31 (8) CARCINOGENESIS 1319-28 (2010) (only abstract provided) ("Dietrich"). 8 S. Ray, Activation of the Ary! Hydrocarbon Receptor by TCDD Inhibits Senescence: a Tumor Promoting Event?, 77(4) BIOCHEM PHARMACOL. 681- 8 (2009) ( only abstract provided) ("Ray"). 9 S. Knerr & D. Schrenk, Carcinogenicity of 2,3, 7,8-tetrachlorodibenzo-p- dioxin in Experimental Models, 50(10) MOL NUTR FOOD RES 897-907 (2006)( only abstract provided) ("Knerr"). 10 A. Nyska et al., Exocrine Pancreatic Pathology in Female Harlan Sprague-Dawley Rats After Chronic Treatment with 2,3, 7,8- tetrachlorodibenzo-p-dioxin and Dioxin-like Compounds, 112(8) ENVIRON HEALTH PERSPECT 903-9 (2004)(only abstract provided) ("Nyska"). 11 JM Ebos et al., Accelerated Metastasis After Short-term Treatment with a Potent Inhibitor of Tumor Angiogenesis, 15(3) CANCER CELL 232-39 (2009) ( only abstract provided) ("Ebos"). 6 Appeal2017-005899 Application 13/954,834 pancreatic cancer with ITE, which Appellant argues DeLuca merely mentions and indicates an expectation that such treatment would be possible. Appeal Br. 9. On balance, we find the evidence of record favors the Examiner's position and are unpersuaded by Appellant's arguments concerning this rejection. DeLuca ( on which present inventor Song is listed as a joint inventor) acknowledges prior research into artificial AhR ligands such as TCDD, and teaches that natural, isolated ITE is useful in treating cancer (as well as other angiogenesis-implicated disorders) and has the advantages of being less prone to induce acquired drug resistance and presenting fewer side-effects than dioxins (like, e.g., TCDD). DeLuca 1 :58-2:6, 5:45---6:5. Further, DeLuca explains that ITE and its analogs, as angiogenesis- inhibiting AhR ligands, "are useful in the treatment of primary and metastatic cancers," intuitively so for solid tumors, but are also expected to be applicable to "virtually[] all types of cancer." Id. at 10:3-15, 10:33-35. Moreover, DeLuca immediately thereafter suggests applying ITE and its analogs to inhibit pancreatic cancer, specifically, because ITE is an AhR agonist and AhR agonists were understood to inhibit pancreatic cancer cell lines with high AhR expression. Id. at 10:24--33 (citing Koliopanos). 12 DeLuca does not merely instruct using ITE and its analogs to treat cancer, but it also teaches proper dosing regimens "can be routinely determined in accordance with pharmacological activity data from in vivo 12 Alexander Koliopanos et al., Increased Ary/hydrocarbon Receptor Expression Offers A Potential Therapeutic Target for Pancreatic Cancer, 21 ONCOGENE 6059-70 (2002) ("Koliopanos"). 7 Appeal2017-005899 Application 13/954,834 experimental models," and that ITE can be paired with pharmaceutically acceptable carriers and administered in essentially any customary way. Id. at 11 :25--41. More specifically, DeLuca disclosed ITE dosages so as to provide patient blood concentrations of 2-10 mg/kg body weight, which can be administered, for example twice daily, are to be continued until the patient is free from the disorder, e.g., cancer, and thereafter can be provided as maintenance dosing. Id. at 11 :48-55. DeLuca disclosed that a dose of 10 mg/kg of body weight was shown to be effective to inhibit angiogenesis, which the reference equates to treating cancer. Id., generally, but specifically 12:50-51. Regarding Appellant's argument that a disclosed genus cannot render a claimed species obvious, the Federal Circuit's holding in In re Baird was premised on a finding that a prior art reference, over which the claims were rejected as obvious, disclosed a generic chemical formula with over 100 million possible species and "there [was] nothing in the disclosure of [ the reference] that one should select such [claimed] variables." Baird, 16 F.3d at 3 83. Here, it is not clear how large the genus of cancers actually is ( the NIH indicates there are more than 100 types), 13 but whatever the number, it is far fewer than 100 million. Further, as contrasted with the facts of Baird, here DeLuca, in addition to discussing using ITE and its analogs for cancer treatment, mentions that AhR agonists, which includes ITE and it analogs, were shown to inhibit pancreatic cancer cell lines with high AhR expression. DeLuca 10:24--33. Thus, unlike Baird, there is a direct suggestion in the reference to treat one of the expressly claimed cancers. 13 NIH, Cancer Types, www.cancer.gov/types (visited May 21, 2018). 8 Appeal2017-005899 Application 13/954,834 Regarding the Song Declaration, we note the inventor is attacking his own prior statements because DeLuca is Dr. Song's own patent. Also, while the Song Declaration addresses a failed attempt to treat lymphoma using ITE, it is not evidence that those of ordinary skill in the art would have even been aware of such a failure or possible shortcoming of ITE so as to be dissuaded from the explicit teachings of DeLuca. Appellant's arguments regarding DeLuca's enablement of cancer treatment are unpersuasive because "a prior art printed publication cited by an examiner is presumptively enabling barring any showing to the contrary by a patent applicant." In re Antor Media Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012). In any event, a reference need not be enabled to qualify as prior art forÂ§ 103 purposes: "UnderÂ§ 103, ... a reference need not be enabled; it qualifies as a prior art, ... for whatever is disclosed therein." Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1357 (Fed. Cir. 2003). The Federal Circuit explained that proof of efficacy is not required for a prior art reference to be enabling for purposes of [ unpatentability] .... [T]he proper issue is whether the [prior art] is enabling in the sense that it describes the claimed invention sufficiently to enable a person of ordinary skill in the art to carry out the invention. Impax Labs., Inc. v. Aventis Pharms. Inc., 468 F.3d 1366, 1383 (Fed. Cir. 2006). Here, DeLuca says ITE will treat cancer and explains why and how. Regarding Appellant's arguments concerning and evidence of unpredictability in the art, we are unpersuaded that the prior art's indicated "failures" or unpredictability with non-ITE compounds, e.g., TCDD (as disclosed by, e.g., Ray, Knerr, and Nyska) or VEGFR/PDGFR, overcome the explicit teaching of DeLuca that ITE and its analogs can be used to treat 9 Appeal2017-005899 Application 13/954,834 cancer at the claimed dosages. Again, without evidence to the contrary, we presume DeLuca enables treating cancer using ITE as it discloses, and treating pancreatic cancer, specifically, as it suggests. Antor Media Corp., 689 F.3d at 1288. Appellant has not presented persuasive evidence to the contrary. Some degree of unpredictability in the art, generally, does not establish there was not a reasonable expectation of success regarding a compound expressly disclosed in the prior art as effective. See Pfizer, 480 F.3d at 1364. Regarding claim 18, Appellant argues "[ c ]laim 18 does not recite pancreatic cancer" and, therefore, the claim is not obvious over DeLuca (in view of Consumer Reports). Appeal Br. 18. This argument is not persuasive. As discussed above, while DeLuca suggests treating pancreatic cancer with ITE or an analog thereof, it expressly discloses treating cancer. Thus, DeLuca's disclosure of treating cancer with ITE is not restricted to only pancreatic cancer, but includes "all types of cancer" because all types of cancer involve angiogenesis. See DeLuca 10: 14--15. Regarding claim 7, Appellant argues: DeLuca et al. in view of Consumer Reports News does not teach or suggest orally administering a dose of water in an amount sufficient to reduce feces hardening due to the administration of ITE or one of its structural analogs. DeLuca et al. in view of Consumer Reports News is completely silent regarding feces hardening due to the administration of ITE or one of its analogs and, accordingly, is also completely silent regarding administering water in an amount sufficient to reduce feces hardening. Appeal Br. 18. 10 Appeal2017-005899 Application 13/954,834 We note the Specification illuminates what is meant by the claimed "administering orally a dose of water to the subject in addition to normal water uptake by the subject in an amount sufficient to reduce feces hardening." At paragraph 45, the Specification states, "extra water is administered orally, in addition to normal daily water drinking, to alleviate an ITE dosing complication due probably to the hardening of feces. A daily dose of 20 ml/kg of water administered orally in a short period of time is proposed preliminarily." We note that, for a human subject weighing about 70 kg ( about 154 lbs), this amounts to about 1.4 L ( about 4 7 fluid ounces) of water. While we do not interpret the claim to be limited to this specific amount of water, it indicates generally what amount falls within the scope of claim 7. We agree with the Examiner that Consumer Reports suggests drinking water to take medications orally, even "plenty of water" if taking bisphosphonates, but conclude it is not reasonable that one would drink an amount such as claimed based on the reference. Other than drinking a sufficient amount of water to take medication, Consumer Reports does not suggest drinking significant amounts of water and DeLuca is silent on any need to do so. For the reasons above, we affirm the rejection as to claims 1, 2, 5, 6, 10, 12-14, and 16-18. However, we conclude the Examiner has not established a prima facie case that claim 7 would have been obvious and we reverse the rejection as to this claim. Re} ection over Ahn The Examiner determined the rejected claims would have been obvious over Ahn and, as to claim 7, also combining Consumer Reports. 11 Appeal2017-005899 Application 13/954,834 Final Action 6-7, 11-15 and Answer 7-11, 34--38 (collectively citing Ahn at 1--4, 6, 9, 15, 28, 36, Figure 4). Appellant argues Ahn does not teach ITE, at 200 mg/kg, would predictably treat skin, colorectal, stomach, pancreatic, kidney, bladder, soft tissue, or cervical cancer ( or any type of cancer). Appeal Br. 21. Appellant contends that the "high ICso levels" (58,500 and 90,400 nM) indicated in Ahn Table 1 (at 32) for ITC doses for cancer treatment are confirmed by Ahn as too high to be efficacious (as compared to the ICso of 859.3 nM for K562/DOX regarding doxorubicin resistance and compared to Ahn's compound 13's IC50 of0.0011---0.35 ÂµM for cancer efficacy). 14 Id. at 21-22; see also id. at 27 (Appellant also argues compound 13 is "very different than ITE"). Appellant argues Ahn does not teach administering ITE at a dosage as low as 200 mg/kg, given its high indicated ICso. Id. at 22-23 (also citing the Song Declaration as evidence that such a low dosage of ITC would not provide adequate ICso according to Ahn). Appellant contends that, because Ahn discloses "excessively high ECso [sic, ICso] for ITE," Appellant has "presented objective evidence showing that the claimed concentrations achieve unexpected results" relative thereto. Id. at 26. Appellant argues the Examiner's reasoning relies on compounds (e.g., 13 and 28, rather than ITE) that are very different from ITE or its analogs to show treating of cancer (via tubulin inhibition). Id. at 27. Appellant argues Ahn "nowhere provides any evidence that ITE would 14 We note, Appellant appears to be confusing the compound 13 IC50 results with their deviation ranges, but the results and deviations are similarly comparatively low values, in context. See Ahn 33 (Table 1 ). 12 Appeal2017-005899 Application 13/954,834 be efficacious against colon cancer" ( even while other compounds may be). Id. at 28. Appellant argues that, while Ahn may teach using its disclosed compounds for treating cancer, e.g., colon cancer, it does not include ITE among those compounds that would be efficacious for doing so (e.g., no claim identifies ITE, while reciting many other compounds). Id. We initially note there is a dispute as to whether and how Ahn discloses ITE or an analog thereof. The Examiner determined that Ahn's compound 13 is an analog of ITE because it is "similar in structure to ITE." Answer 35. This is in conflict with Appellant's arguments, which are generally premised on the contention that compound 13 is not ITE or an analog thereof, as Appellant contrasts the performance of a disclosed I-8 compound !TE/analog (the IC50) with that of compound 13 to distinguish between ITE and non-ITE compounds as disclosed by Ahn. The Specification expressly defines what is meant by the claimed ITE or one of its "structural analogs" at paragraph 37, which states "the term 'structural analog' or simply 'analog' of ITE is defined as a compound with chemical structure similar to that of Ah receptor endogenous ligand ITE and with a capability of binding to the Ah receptor." Whether or not a compound can be said to have a chemical structure similar to another compound is somewhat subjective, but, here, the Examiner has not presented any evidence that Ahn's compound 13, or any other compound of Ahn, has the "capability of binding to the Ah receptor." Therefore, we agree with Appellant that the Examiner has not satisfied the burden of demonstrating that Ahn's compound 13 falls within the scope of the claims. In re Oetiker, 977 F .2d at 1445 ("[T]he examiner bears the initial burden ... of presenting 13 Appeal2017-005899 Application 13/954,834 a prima facie case of unpatentability. "). Appellant, however, concedes that Ahn's compound I-8 is (within the scope of) the claimed ITE or an ITE analog. Appeal Br. 21; Reply 6. Regarding Appellant's arguments that Ahn does not teach or suggest the claimed dosage of 1-200 mg/kg of !TE/analog to treat cancer, we find Appellant's arguments persuasive. While Ahn discloses ITE as compound 59 at page 26 and also discloses an ITE analog as compound I-8 at page 32, Ahn indicates ITE was "not yet tested" and provides no data on whether it inhibits cancer cells. Ahn also indicates that for the I-8 compound ITE analog, its IC50 for inhibiting two types of prostate cancer ( cells LNCaP and PC-3) was 58.5 ÂµM (58,500 nM) and 90.4 ÂµM (90,400 nM), respectively. Ahn 32 (Table 1 ). Appellant argues that these IC50 results, especially compared to the orders-of-magnitude-lower ICso results for compound 13, would have suggested to the skilled artisan that !TE/analog I-8 was not effective to treat (at least prostate) cancer. See Appeal Br. 21-22. The Examiner's position is that an ICso result indicates some inhibition effectiveness at some concentration/ dosage and, thus, means that the compound is effective at treating cancer to some degree, thus meeting the claim. See Answer 36. The Examiner's determination that the claimed dosage would have been obvious over Ahn is premised on a conclusion that the skilled artisan could have easily optimized the dosage, as indicated by Ahn at 15 ("It is well within the skill of an artisan to determine dosage .... "). Answer 36. Appellant argues that the Ahn I-8 compound ICso results (Table 1) would especially indicate to a skilled artisan that a dosage as low as claimed (i.e., 14 Appeal2017-005899 Application 13/954,834 no more than 200 mg/kg) would not be effective. Appeal Br. 22. Appellant presents evidence in the Song Declaration that even at a dosage level 50% higher than claimed, i.e., 300 mg/kg, the maximum blood levels of ITC observed in test subjects only reached 3.6 ÂµM (3,600 nM), which was far lower (by orders of magnitude) than the IC50 results for the I-8 compound ITE analog of Ahn. Appeal Br. 22-23; Song Declaration ,r,r 6-9. We conclude that even if Ahn suggests that some dosage of ITE or an ITE analog may treat cancer and also discloses that dosage is an optimizable variable, the evidence supports that it would not have been obvious for the skilled artisan to modify (optimize) dosages to effect a blood concentration of ITE/ analog toward the range of the claims, but it would suggest just the opposite. Appellant's evidence supports that only a much higher dosage of the compound than the 300 mg/kg dosage tested (as discussed in the Song Declaration) and the 200 mg/kg claimed would be expected to achieve some efficacious result in cancer treatment based on the Ahn disclosure, so Ahn would provide little motivation to modify a dosage to be lower and within the claimed range. For the reasons above, we find the balance of evidence supports Appellant's position and reverse the rejection over Ahn. 15 Appeal2017-005899 Application 13/954,834 SUMMARY The rejection of claims 1, 2, 5, 6, 10, 12-14, and 16-18 under 35 U.S.C. Â§ 103(a) over DeLuca and Consumer Reports is affirmed. The rejection is reversed as to claim 7. The rejection of claims 1, 2, 5-7, 10, 12-14, 17, and 18 under 35 U.S.C. Â§ 103(a) over Ahn and Consumer Reports is reversed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. Â§ 1.136(a)(l )(iv). AFFIRMED-IN-PART 16