Ex Parte Hyde et alDownload PDFPatent Trial and Appeal BoardJul 11, 201611900051 (P.T.A.B. Jul. 11, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 111900,051 0910712007 Roderick A. Hyde 80118 7590 07112/2016 Constellation Law Group, PLLC P.O. Box 580 Tracyton, WA 98393 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. SEl-0907-US 1624 EXAMINER BRUSCA, JOHNS ART UNIT PAPER NUMBER 1631 MAILDATE DELIVERY MODE 07/12/2016 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte RODERICK A. HYDE, MURIEL Y. ISHIKAWA, ERIC C. LEUTHARDT, DENNIS J. RIVET, and LOWELL L. WOOD, JR. Appeal2014-005452 Application 11/900,051 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and TA WEN CHANG, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal 1 under 35 U.S.C. § 134 involving claims to a method of determining, in a computing device, a similarity or a dissimilarity between at least one aspect of epigenetic information of a first individual and at least one aspect of epigenetic information of a second individual. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 Appellant identifies the Real Party in Interest as Searete LLC (see App. Br. 5). Appeal2014-005452 Application 11/900,051 Statement of the Case Background "Epigenetic information may include, for example, information regarding DNA methylation, histone states or modifications, DNA structure, transcriptional activity, RNAi, protein binding or other molecular states" (Spec. 8:8-10). "Epigenetic phenotype information may be stable over time in multiple assays or it may alter over time" (Spec. 9: 16-17). The Claims Claims 1, 3---6, 14, 15, 17-20, 24, 25, 28, 29, 31-34, 38, 39, 43--48, 50, 51, 53, 55, 56, 59 and 61---64 are on appeal. Independent claim 1 is representative and reads as follows: 1. A method comprising: determining, in a computing device, a similarity or a dissimilarity between at least one aspect of epigenetic phenotype information regarding at least one first individual and at least one aspect of epigenetic phenotype information regarding at least one second individual, wherein the at least one second individual had been previously influenced by at least two epigenetic influencing events including both a medical radiation therapy and an environmental event including exposure to one or more pollutants; statistically correlating the at least one aspect of epigenetic phenotype information regarding at least one second individual with previous epigenetic information regarding the at least one second individual, wherein the previous epigenetic information was ascertained prior to both of the at least two epigenetic-influencing events; and communicating the similarity or the dissimilarity and the statistical correlation to at least one user. 2 Appeal2014-005452 Application 11/900,051 The Issues A. The Examiner rejected claims 1, 3, 5, 6, 14, 15, 17, 19, 20, 24, 25, 28, 29, 31, 33, 34, 38, 39, 43--46, 48, 50, 51, 53, 55, 56, 59, 61 and 62 under 35 U.S.C. 103(a) over Esteller 20092, Hegi3, Esteller 20004 and Sutherland5 (Ans. 3-8). B. The Examiner rejected claims 1, 4, 15, 18, 29 and 32 under 35 U.S.C. 103(a) over Esteller 2009, Hegi, Esteller 2000, Sutherland and Li6 (Ans. 8- 10). C. The Examiner rejected claims 63 and 64 under 35 U.S.C. 103(a) over Esteller 2009, Hegi, Esteller 2000 and Digel7 (Ans. 10-14). Because the same issues are dispositive for all three rejections, we will consider them together. The issue with respect to these rejections is: Does the evidence of record support the Examiner's conclusion that Esteller 2009, Hegi and 2 Esteller, US 2009/0047214, published Feb. 19, 2009. 3 Hegi et al., MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma, 352 NEW ENGLAND J. MED. 997- 1003 (2005). 4 Esteller et al., Inactivation of the DNA-Repair Gene MGMT and the Clinical Response of Gliomas to Alkylating Agents, 343 NEW ENGLAND J. MED. 1350-1354 (2000). 5 Sutherland et al., Epigenetics and the Environment, 983 ANNALS NEWYORKACAD. SCI. 151-160 (2003). 6 Li et al., Epigenetic Changes in Prostate Cancer: Implication for Diagnosis and Treatment, 97 J. NAT'L CANCER INST. 103-115 (2005). 7 Digel et al., DNA methylation disturbances as novel therapeutic target in lung cancer: Preclinical and clinical results, 55 CRITICAL REV. ONCOLOGY/ HEMATOLOGY 1-11 (2005). 3 Appeal2014-005452 Application 11/900,051 Esteller 2000, combined with either Sutherland, Sutherland and Li, or Digel, render the claims obvious? Findings of fact 1. The Specification teaches that "epigenetic phenotype information includes information regarding DNA methylation, histone states or modifications" (Spec. 9: 12-13). 2. The Specification teaches that an "epigenetic-influencing event" includes an event that influences the epigenetic phenotype of at least one cell within at least one individual ... An epigenetic-influencing event may be part of a medical therapy, for example an epigenetic- influencing event may include one or more medications, or one or more treatments. An epigenetic-influencing event may include at least one medical therapy including one or more energy-based procedures, for example radiation therapy ... An epigenetic-influencing event may include one or more environmental events, such as but not limited to, exposure of an individuai to radiation, one or more poHutants, or one or more toxins. (Spec. 8: 16-23). 3. The Specification teaches that "'mosaicism' ... denotes ... situations where two or more subtypes originate with the first cell of an organism" (Spec. 11 :27-28). 4. Esteller 2009 teaches that for cancers such as colorectal cancer, the presence of aberrant methylation at the WRN promoter predicts improved survival in those patients treated with topoisomerase inhibitors such as irinotecan, a treatment commonly used in this neoplasm. These findings, as discussed in the experimental section below, underline the significance of WRN as a caretaker of our 4 Appeal2014-005452 Application 11/900,051 genome with tumor suppressor activity, and identify epigenetic silencing of WRN as one key step in cancer development that may have an important clinical impact for the treatment of these patients .... Accordingly, in a first aspect, the invention provides a method for predicting the likelihood of successful treatment of cancer with a topoisomerase inhibitor and/or a DNA damaging agent and/or a DNA methyltransferase inhibitor and/or a HDAC inhibitor comprising determining the methylation status of a RecQ helicase family gene in a sample obtained from a subject, wherein if the RecQ helicase family gene is hypermethylated the likelihood of successful treatment is higher than if the RecQ helicase family gene is unmethylated, or methylated to a lesser degree. Preferably, the methylation status of at least the WRN gene is determined. (Esteller 2009 i-fi-1 7-8). 5. Esteller 2009 teaches that we assessed if the presence of WRN promoter hypermethylation was a predictive marker of response to irinotecan in colorectal cancer patients treated with this drug. We selected a similar number of WRN-hypermethylated (n=45) and unmethylated (n=43) primary colorectal tumors from patients treated with irinotecan where a long clinical follow-up was available. We found that the median time to the death of the patient was 39.4 months for WRN methylated colon tumors and just 20. 7 months for WRN unmethylated colon tumors. Thus, the presence of WRN CpG island promoter hypermethylation was a significant strong predictor of increased overall survival in colon cancer patients treated with irinotecan (Kaplan-Meier p=0.00005; 95% confidence interval 25.4-35.2) (Esteller 2009 i-fi-1209-210). 5 Appeal2014-005452 Application 11/900,051 6. Esteller 2009 teaches that "[a]ll statistical analyses were performed using the SPSS version 10.1 program" (Esteller 2009 ii 196). 7. Esteller 2000 teaches that: In our study, methylation of the MGMT promoter was associated with responsiveness to carmustine and an increase in overall survival at the time to progression of disease. Moreover, the methylation status of the promoter was more predictive of the outcome of carmustine treatment than the grade of tumor, the Kamofsky performance status, or the patient's age. (Esteller 2000 1353, col. 1 ). 8. Figure 3 of Esteller 2000 is reproduced below: A B h '!!I \~ ... Me~hyia!ed ~ .!':! 60 .____,___, a ro 5 P<0.001 '1_ ~ °' 0 i .0...<.i- AA ~ ~ .£- 20 l ~ ; ~ ;;j L.t',nmethyl;rt.,d ~ j- 1 ; • > • • t i t t t t • , b < , t t t t • , , t t '> ! • • • ' • t () 5 12 18 u 30 36 Months Months No. oF SueJECTs No. o~ Su SJEtTs Methylat~ci 18 19 19 18 1:'l Meihy1~1ed 19 1s 18 14 9 3 Unmethyloteci 28 28 16 19 5 U"methyla!ed 28 lZ 7 Figure 3 depicts: Overall Survival (Panel A) and Time to the Progression of Disease (Panel B) among Patients with Gliomas Treated with Carmustine, According to the Methylation Status of the MGMT Promoter. Both overall survival and the time to the progression of disease were significantly greater in the group of patients with methylation of the MGMT promoter than in the group without methylation. (Esteller 2000 1353, col. 2). 6 Appeal2014-005452 Application 11/900,051 9. Esteller 2000 teaches Statistical Analysis ... In univariate analyses, methylation of the promoter was positively correlated with the clinical response and with overall and disease-free survival ... The lack of methylation was associated with a much higher risk of death (hazard ratio, 9.5; 95 percent confidence interval, 3.0 to 42.7; P<0.001) (Fig. 3A). In univariate analysis, no other factor had a statistically significant relation with survival. (Esteller 2000 1352, col. 1-2). 10. Esteller 2000 teaches that "Analyses were performed with the use of JMP software (version 3.1, SAS Institute, Cary, N.C.) and Stata software" (Esteller 1352, col. 2). 11. Esteller 2000 teaches that "[t]umor specimens were obtained by resection or biopsy peformed before the initiation of treatment with radiation and chemotherapy ... The response to treatment was evaluated after the patients had completed therapy" (Esteller 2000 1351, col. 1-2). 12. Hegi teaches that Our data suggest that the methylation status of the MGMT promoter may have prognostic value and, in addition, may be a clinically significant predictor of benefit from temozolomide chemotherapy ... Determination of MGMT promoter methylation status by methylation-specific PCR may allow the selection of patients most likely to benefit from temozolimide treatment; patients whose tumors are not methylated at the MGMT promoter appear to derive little or no benefit from the addition of temozolimide to radiotherapy ... Stratification according the MGMT promoter methylation status may be considered in future trials in which temozolomide or other alkylating agents are used. (Hegi 1002, col. 1-2). 7 Appeal2014-005452 Application 11/900,051 13. Hegi teaches that among patients with promoter methylation who were assigned to receive both temozolomide and radiotherapy ... two-year survival rate was 46.0 percent, as compared with 22.7 percent among those with MGMT promoter methylation who were assigned to radiotherapy alone. Kaplan-Meier estimates of overall survival in these two subgroups were significantly different (P=0.007 by the log-rank test) ... In the group of patients whose tumors contained a methylated MGMT promoter, those who received temozolomide and radiotherapy had a median progression-free survival of 10.3 months, as compared with 5.9 months for patients who received radiotherapy alone (P=0.001). Among the patients whose tumors contained an unmethylated MGMT promoter, those who received temozolomide and radiotherapy had a median progression-free survival of 5.3 months, as compared with 4.4 months for patients who were treated with radiotherapy alone (P=0.02) (Hegi 1000, col. 1-2). 14. Sutherland teaches "[ n ]ickel is a potent human carcinogen that has been shown to alter DNA methylation patterns and affect histone acetylation ... it has been proposed that arsenic metabolism may deplete intracellular methyl group stores and thereby lead to changes in DNA methylation that may be involved in carcinogenesis." (Sutherland, abstract). 15. Table 1 of Li teaches that "epigenetic aberrations in prostate cancer" include "[h ]istone methylation" (Li 104, Table 1 ). 16. Digel teaches that "[ e ]xposure to tobacco carcinogens has been associated with DNA methylation .... Tobacco-specific carcinogens further induced methylation of the p 16 promoter region in adenocarcinomas . . . In this experimental rat model, the prevalence of p 16 methylation increased 8 Appeal2014-005452 Application 11/900,051 with disease progression from cell hyperplasia to metaplasia and then to carcinoma in situ" (Digel 4, col. 1-2). Principles of Law "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR!nt'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability." Id. at 417. Analysis We adopt the Examiner's findings of fact and reasoning regarding the scope and content of the prior art (Ans. 3-14; FF 1-15) and agree that the claims are rendered obvious by Esteller 2009, Hegi and Esteller 2000, combined with either Sutherland, Sutherland and Li, or Digel. We address Appellants' arguments below. Claim 1 We have considered, but are not persuaded by Appellants' arguments that "the Examiner did not establish a prima facie case of obviousness against independent claim 1 for the reason that he failed to show that the entirety of all three clauses of the claims are taught by any of the five cited references, taken alone or in combination" (App. Br. 21 ). Esteller 2009 teaches comparing at least one aspect of epigenetic information (FF 4). Specifically, Esteller 2009 teaches determining hypermethylation by analyzing "a similar number of WRN-hypermethylated (n=45) and unmethylated (n=43) primary colorectal tumors from patients treated with irinotecan" (FF 5) and statistically finding that "promoter 9 Appeal2014-005452 Application 11/900,051 hypermethylation was a significant strong predictor of increased overall survival" (FF 5). Esteller 2009 teaches that these statistical analyses were performed using a computer software program (FF 6). Esteller 2009 communicates the result and statistical correlation to the reader (FF 4---6). Thus, Esteller 2009 performs a method with a "determining" step, a "statistically correlating" step, and a "communicating" step that analyze epigenetic phenotype information regarding multiple individuals (FF 4---6). As the Examiner notes, Esteller 2009 differs from claim 1 in the specific "epigenetic-influencing events" and in making an analysis prior to the "epigenetic-influencing events" (see Ans. 5). Esteller 2000 also analyzes epigenetic information, specifically regarding the MGMT promoter (FF 7) in different patient populations (FF 8) using statistical methods (FF 9) and computer software (FF 10). Esteller 2000 specifically teaches obtaining and evaluating specimens before and after radiation and chemotherapies (FF 11) where radiation and chemotherapy expressly fall within the scope of "epigenetic-influencing events" as defined by the Specification (FF 2), rendering it obvious to compare tumor specimens before and after treatment using the epigenetic information of Estell er 2000. Hegi also teaches that DNA methylation may be influenced by medications or radiation therapy, and similarly teaches comparing methylation status of individuals in association with radiation (FF 12-13). Sutherland teaches that environmental pollutants and carcinogens, such as nickel and arsenic, similarly lead to changes in DNA methylation (FF 14). 10 Appeal2014-005452 Application 11/900,051 The Examiner reasons that it would have been obvious "to measure epigenetic information prior to initiation of a medical therapy because Esteller et al. 2000 shows measurement of epigenetic information prior to initiation of therapy, and because such measurement would allow for determination of the suitability of a medical therapy for a patient" (Ans. 7). The Examiner further explains that the prior art "provide guidance that further study of association of methylation of promoters of either the WRN promoter or the MGMT promoter is desirable to establish prognostic assays for cancer patients that undergo chemotherapy combined with radiation therapy" (Ans. 7). Therefore, the Examiner has provided "articulated reasoning with some rational underpinning to support the legal conclusion of obviousness," see In re Kahn, 441F.3d977, 988 (Fed. Cir. 2006), cited with approval inKSR, 550 U.S. at 417-18 (2007). We recognize that Appellants repeatedly contend that the Examiner fails to demonstrate teachings of the prior art for the limitations of claim 1 at pages 22-36 of the Appeal Brief, but our careful review of Appellants' arguments finds them unpersuasive, 8 in particular as they fail to address the prior art in combination. "Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references .... [A reference] must be read, not 8 We must separately note that the clause 3 argument is particularly spurious, given that each of the references themselves represent widely published communications that detail statistical correlations regarding epigenetic information in different patient populations (FF 5, 9, 13-16). 11 Appeal2014-005452 Application 11/900,051 in isolation, but for what it fairly teaches in combination with the prior art as a whole." In re Merck& Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Claims 3-6 and 14 We are further not persuaded by Appellants' allegations that "the Examiner failed to establish a prima facie case of obviousness for any of claims 3---6 and 14 by any combination of references" (App. Br. 37). Specifically, regarding claim 3, the cited prior art is replete with teachings regarding DNA methylation information including teachings by Esteller 2009 regarding DNA methylation (FF 4). Regarding claim 4, we note that the Examiner addressed this rejection further in view of Li, which teaches epigenetic information regarding histone structure (FF 15). We further agree with the Examiner's rationale, regarding claim 5, that it would have been "obvious to analyze multiple loci because Esteller 2009 shows the relevance of the WRN promoter methylation to chemotherapy, and Hegi et al. and Esteller et al. 2000 show the relevance of methylation of a second locus, the MGMT promoter, to chemotherapy" (Ans. 7). Regarding claim 6, per Appellants' definition of mosaicism (FF 3), Esteller 2009, Hegi and Esteller 2000 all show evidence of mosaicism (FF 4--12). Regarding claim 14, Esteller 2009 further teaches an intervention strategy (FF 4). Claim 15 We recognize, but find unpersuasive Appellants' argument that "the Examiner did not make a prim a facie case of obviousness for independent claim 15 or its dependent claims over any combination of references" (App. Br. 37). 12 Appeal2014-005452 Application 11/900,051 The skilled artisan would have found it obvious that analysis using JMP software and Stata software, as taught by Esteller 2000 (FF 11 ), employs a system comprising at least one computer program on recordable- type media for use with at least one computer system and wherein the computer program includes a plurality of instructions. Moreover, it would have been obvious to employ a computer in the method of claim 1, already found obvious above, in order "to update it using modem electronic components in order to gain the commonly understood benefits of such adaptation, such as decreased size, increased reliability, simplified operation, and reduced cost." Leapfrog Enterprises Inc. v. Fisher-Price Inc., 485 F.3d 1157 (Fed. Cir. 2007). Claims 17-20, 24, 25 and 28 We are further not persuaded by Appellants' allegations that "the Examiner failed to establish a prima facie case of obviousness for any of claims 17-20, 24--25, and 28 by any combination of references" (App. Br. 57). Specifically, dependent claims 17-20 and 28 mirror information as addressed above for dependent claims 3---6 and 14. Regarding claim 24, Esteller 2009 (FF 4), Esteller 2000 (FF 7) and Hegi (FF 13) teach medication. Per claim 25, Sutherland teaches exposure to one or more toxins (FF 14). Thus, the ordinary artisan would have reasonably employed information, as recited by claims 17-20, in a system with instructions for epigenetic-influencing events, as recited by claims 24 and 25, and for giving instructions for suggesting an intervention strategy, as recited by claim 28, 13 Appeal2014-005452 Application 11/900,051 consistent with the Examiner's reliance on Esteller 2009, Esteller 2000, Hegi and Sutherland alone, or further in view of Li (see Ans. 3-10). Claim 29 We recognize, but find unpersuasive Appellants' argument that "the Examiner did not make a prim a facie case of obviousness for independent claim 29 or its dependent claims over any combination of references" (App. Br. 58) for the reasons given above. Claims 31-34, 38 and 39 We recognize, but find unpersuasive Appellants' argument that "the Examiner failed to establish a prima facie case of obviousness for any of claims 31-34 and 38-39 by any combination of references" (App. Br. 77) because the rejection relied on a combination of prior art references, which in their combined teachings would have suggested to a person of ordinary skill in the art the claimed invention. Specifically, dependent claims 31-34 and 45 mirror information as addressed above for dependent claims 3---6 and 25. Regarding claim 44, Hegi teaches radiation (FF 12). Thus, the ordinary artisan would have reasonably employed information, as recited by claims 31-34, in a system with instructions for epigenetic-influencing events, as recited by claims 38 and 39, consistent with the Examiner's reliance on Esteller 2009, Esteller 2000, Hegi and Sutherland alone, or further in view of Li (see Ans. 3-10). Claim 43 We recognize, but find unpersuasive Appellants' argument that "the Examiner did not make a prima facie case of obviousness for independent 14 Appeal2014-005452 Application 11/900,051 claim 43 or its dependent claims over any combination of references" (App. Br. 77) for the reasons given above. Claims 44-46 and 48 We recognize, but find unpersuasive Appellants' argument that "the Examiner failed to establish a prima facie case of obviousness for any of claims 44--46 and 48 by any combination of references" (App. Br. 95) because the rejection relied on a combination of prior art references, which in their combined teachings would have suggested to a person of ordinary skill in the art the claimed invention. Specifically, dependent claims 44--46 mirror information as addressed above for dependent claims 3 8, 25 and 3. Regarding claim 48, Hegi teaches that methylation status may have prognostic value (FF 12). Thus, the ordinary artisan would have reasonably employed information, as recited by claim 46, in a system with instructions for epigenetic-influencing events, as recited by claims 44 and 45, and predicting at least one epigenetic event, as recited by claim 48, consistent with the Examiner's reliance on Esteller 2009, Esteller 2000, Hegi and Sutherland (see Ans. 3-8). Claim 50 We recognize, but find unpersuasive Appellants' argument that "the Examiner did not make a prima facie case of obviousness for independent claim 43 or its dependent claims over any combination of references" (App. Br. 77) substantially for the reasons given above. Regarding clause 2 of this claim, we note that it nearly completely mirrors clause 2 of claim 15, which we addressed above, but in addition specifies the epigenetic influencing 15 Appeal2014-005452 Application 11/900,051 events to be medical radiation and exposure to pollutants, which we addressed above in relation to claims 38 and 25. Claims 51, 53 and 55 We recognize, but find unpersuasive Appellants' argument that "the Examiner failed to establish a prima facie case of obviousness for any of claims 51, 53 and 55 by any combination of references" (App. Br. 111) because the rejection relied on a combination of prior art references, which in their combined teachings would have suggested to a person of ordinary skill in the art the claimed invention. Specifically, dependent claim 53 mirrors information as addressed above for dependent claims 3. Regarding claim 55, intervention therapy was addressed for at least claims 14 and 28. Regarding claim 51, we note that it combines information addressed above for claims 24 and 3 8. Claim 56 We recognize, but find unpersuasive Appellants' argument that "the Examiner did not make a prim a facie case of obviousness for independent claim 56 or its dependent claims over any combination of references" (App. Br. 111) for the reasons given above. Claims 59, 61 and 62 We recognize, but find unpersuasive Appellants' argument that "the Examiner failed to establish a prima facie case of obviousness for any of claims 59, 61 and 62 by any combination of references" (App. Br. 127). Specifically, dependent claims 59 mirrors information as addressed above for dependent claims 3. Regarding claim 62, intervention therapy was addressed for at least claims 14 and 28. Regarding claim 61, we note that 16 Appeal2014-005452 Application 11/900,051 Sutherland teaches that arsenic may lead to changes in DNA methylation and may be involved in carcinogenesis (FF 14), which is indicative of predicting an environmental event influencing an individual. Claim 63 We recognize, but find unpersuasive Appellants' argument that "the Examiner did not make a prim a facie case of obviousness for independent claim 63 or its dependent claims over any combination of references" (App. Br. 127) for the reasons given above. In particular regarding limitation 4, intervention therapy was addressed for at least claims 14 and 28, and the skilled artisan would have found this information pertinent for comparison between multiple patients. Digel also discloses that exposure to tobacco carcinogens has been associated with DNA methylation, that the prevalence of p 16 methylation increased with disease progression from cell hyperplasia to metaplasia and then to carcinoma in situ, and that tobacco smoking leads to frequent epigenetic silencing of the p 16 gene in non-small cell lung cancers (FF 16). Claim 64 We recognize, but find unpersuasive Appellants' argument that "the Examiner did not make a prim a facie case of obviousness for independent claim 64 or its dependent claims over any combination of references" (App. Br. 145) for the reasons given above. Technical rationale to combine Appellants further contend failure to articulate a technical rationale to combine (App. Br. 159), but articulates facts that seem to belong to a 17 Appeal2014-005452 Application 11/900,051 different case, i.e. reference to nine references, reference to treating patients with UV radiation. According, these arguments are not deemed pertinent. Logical consistency We recognize, but find unpersuasive Appellants' contention of a lack of logical consistency in view of the Examiner's rejections based on different combinations of references (App. Br. 160). The Examiner provided detailed reasoning explaining the rationale behind the rejections (see Ans. 3-14). Rule 104 We are further not persuaded by Appellants' arguments that the Examiner failed to "'clearly explain' '[t]he pertinence of the six cited references"' (App. Br. 161). We find that the Examiner met the required burden of presenting "articulated reasoning with some rational underpinning to support the legal conclusion of obviousness", see In re Kahn, 441 F.3d at 988, based on the combination of references (see Ans. 3-14). SUMMARY We affirm the rejection of claims 1, 3, 5, 6, 14, 15, 17, 19, 20, 24, 25, 28, 29, 31, 33, 34, 38, 39, 43--46, 48, 50, 51, 53, 55, 56, 59, 61 and 62 under 35 U.S.C. § 103(a) as obvious over Esteller 2009, Hegi, Esteller 2000 and Sutherland. We affirm the rejection of claims 1, 4, 15, 18, 29 and 32 under 35 U.S.C. § 103(a) as obvious over Esteller 2009, Hegi, Esteller 2000, Sutherland and Li. 18 Appeal2014-005452 Application 11/900,051 We affirm the rejection of claims 63 and 64 under 35 U.S.C. § 103(a) as obvious over Esteller 2009, Hegi, Esteller 2000 and Digel. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 19 Copy with citationCopy as parenthetical citation