Ex Parte Padmanabhan et alDownload PDFPatent Trials and Appeals BoardApr 15, 201914437434 - (D) (P.T.A.B. Apr. 15, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 14/437,434 04/21/2015 Radhakrishnan Padmanabhan 23370 7590 04/17/2019 KILPATRICK TOWNSEND & STOCKTONLLP Mailstop: IP Docketing - 22 1100 PEACHTREE STREET SUITE 2800 ATLANTA, GA 30309 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. G2440-94191 l (034US1) 1391 EXAMINER CRAIGO, BAHAR ALA WI ART UNIT PAPER NUMBER 1623 NOTIFICATION DATE DELIVERY MODE 04/17/2019 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): ipefiling@kilpatricktownsend.com KTSDocketing2@kilpatrick.foundationip.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte RADHAKRISHNAN PADMANABHAN, TADAHISA TERAMOTO, and MARK MANZANO Appeal2018-006480 Application 14/437,434 Technology Center 1600 Before DEMETRA J. MILLS, ROBERT A. POLLOCK, and DAVID COTTA, Administrative Patent Judges. MILLS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a). The Examiner has rejected the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ). We affirm-in-part. Appeal2018-006480 Application 14/437,434 STATEMENT OF CASE The Specification discloses methods of treating a Flavivirus infection by administering a therapeutically effective amount of Flavivirus inhibitors, such as the Flavivirus protease inhibitor of Compound VI (Tolcapone ): or a pharmaceutically acceptable salt thereof. Spec. 4--5. The following claims are representative. 1. A method of treating a Flavivirus infection in a subject, comprising administering to the subject a therapeutically effective amount of a compound selected from the group consisting of: 2 Appeal2018-006480 Application 14/437,434 or a pharmaceutically acceptable salt thereof, wherein the compound inhibits a Flavivirus protease. 8. The method of claim 1, wherein the Flavivirus is the West Nile Virus. 14. The method of claim 1, further comprising administering a second compound or composition, wherein the second compound or composition includes an antiviral compound. 3 Appeal2018-006480 Application 14/437,434 15. The method of claim 14, wherein the second compound or composition is a protease inhibitor. 16. A method of inhibiting a Flavivirus protease in a cell, comprising: contacting a cell with an effective amount of a compound selected from the group consisting of: , and or a pharmaceutically acceptable salt thereof. Cited References Padmanabhan et al., ("Padmanabhan") WO 2010/039538 A2 April 8, 2010 R. Pahwa et al., Practice Parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia, American Academy of Neurology, pp. 983-95 (2006). ("Pahwa") Stewart A. Factor, Treating the "off" periods in Parkinson's, Parkinson's Disease Foundation (2016). ("Factor") Paul J. Carson, Long-Term Clinical and Neuropsychological Outcomes of West Nile Virus Infection, Infectious Diseases Society of America, pp 723-30 (2006). ("Carson") 4 Appeal2018-006480 Application 14/437,434 Grounds of Rejection 1. Claims 1 and 8 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Pahwa as evidenced by Factor in view of Carson. 2. Claims 1, 8, 14--16, and 24--26 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Pahwa as evidenced by Factor in view of Carson and Padmanabhan. FINDINGS OF FACT The Examiner's findings of fact are set forth in the Answer at pages 3-9. The following facts are highlighted. 1. Pahwa et al. teach administering the drug tolcapone (i.e., the same as instant compound VI) 1, in connection with the treatment of Parkinson disease, and that the drug was found to be effective in decreasing off time (p.986, Table 1 and p.989, second paragraph). Final Act. 2 4. According to Pahwa, off time "refers to periods of return of [Parkinson disease] symptoms when medication effect wears off." (p.984, col. 1 ). 2. Pahwa et al. teach that tolcapone is a catechol-0-methyl transferase (COMT) inhibitor (p.989, second paragraph 3. As evidenced by Factor, "'off time is defined as 'a state of decreased mobility"' (second paragraph). Id. 1 Appellants do not contest that Compound IV as set forth in independent claims 1 and 16 is tolcapone. See Spec. p. 5. 2 Office Action mailed June 9, 2017 ("Final Act."). 5 Appeal2018-006480 Application 14/437,434 4. Pahwa et al. do not expressly disclose administering tolcapone to a patient having West Nile Virus (instant claim 1 ). Id. 5. Carson et al. teach that movement disorders have been reported in patients having West Nile Virus infection (p. 728, second paragraph). Carson et al. teach that the studies citing the movement disorders describe features consistent with Parkinsonism (p.728, second paragraph). Id. 6. Carson et al. teach that movement disorders include bradykinesia, rigidity, and postural instability (p.728, second paragraph). Id. 7. The Specification pages 12-13 states that, As used herein the terms treatment, treat, or treating refer to a method of reducing or delaying one or more symptoms of a Flavivirus infection. Thus in the disclosed method, treatment can refer to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity or progression of one or more symptoms of the disease or condition. For example, a method for treating a disease is considered to be a treatment if there is a 10% reduction in one or more symptoms or signs of the Flavivirus infection in a subject as compared to a control. PRINCIPLES OF LAW In making our determination, we apply the preponderance of the evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427 (Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings before the Office). "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'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007). 6 Appeal2018-006480 Application 14/437,434 Moreover, "obviousness requires a suggestion of all limitations in a claim." CFMT, Inc. v. Yieldup Intern. Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003) (citing In re Royka, 490 F.2d 981,985 (CCPA 1974)). Obviousness Rejection 1 - Claims 1, 8 Based on finding of fact 1-7 above, the Examiner concludes that It would have been obvious at the time the invention was made to administer tolcapone to a subject infected with West Nile Virus [WNV] to treat Parkinson-type mobility disorders. * * * The recitation "treating ... a Flavivirus infection" is defined in the instant Specification as "reducing or delaying one or more symptoms of a Flavivirus infection" (see paragraph [0047] of the instant PGPub). The symptoms of West Nile Virus infection include the same or similar symptoms of Parkinson's disease, so much so, that Carson et al. refer to the mobility disorders observed in WNV patients as "parkinsonism". The ordinary artisan would have been motivated to treat WNV infected patients having parkinsonism by administering tolcapone because Pahwa et al. teach tolcapone can reduce "off' time, the state of decreased mobility in patients with Parkinson's disease. Final Act. 4, 5. Appellants contend that, "[ n Jone of the cited references disclose or suggest a method of treating a Flavivirus infection in a subject comprising administering to the subject a therapeutically effective amount of the recited compounds ( e.g., tolcapone) or a pharmaceutically acceptable salt thereof, wherein the compound inhibits a Flavivirus protease." App. Br. 8. Appellants also argue that, "[t]he Examiner also failed to demonstrate that the limitation at issue is the natural result of the combination of elements explicitly disclosed by the prior art references. The claim language requires 7 Appeal2018-006480 Application 14/437,434 the presence of a Flavivirus protease within the subject (i.e., the subject is infected with a Flavivirus). Id. ANALYSIS Claims 1 and 8 In response to the election of species made in an Office Action dated October 12, 2016, Appellants elected compound VI (tolcapone), and West Nile Virus as thejlavivirus. Appellants' Response dated January 12, 2017, p. 7. When the Examiner has required the applicant to elect single chemical species for examination, the issue on appeal is the patentability of the single elected species. It is appropriate to limit discussion to that single issue and take no position respecting the patentability of the broader generic claims, including the remaining, non-elected species. See, Ex parte Ohsaka, 2 USPQ2d 1461 (Bd. Pat. App. Int. 1987). Appellants do not argue individual claims of rejection 1, therefore we select claim 1 as representative claim for this rejection. We agree with the Examiner's fact finding, statement of the rejection and responses to Appellants' arguments as set forth in the Answer. We find that the Examiner has provided evidence to support a prima facie case of obviousness. We provide the following additional comments on the Examiner's argument set forth in the Final Rejection and Answer. Claim Interpretation Claim 1 is directed to, "a method of treating a Flavivirus infection in a subject." We look to the Specification to determine the meaning of the term "treating" as claimed. During ex parte prosecution, claims are to be given their broadest reasonable interpretation consistent with the description of the 8 Appeal2018-006480 Application 14/437,434 invention in the specification. See, Cuozzo Speed Technolgies, LLC v. Lee, 136 S. Ct. 2131, 2144 (2016); In re Zletz, 893 F.2d 319, 321 (Fed. Cir. 1989). The Specification, pages 12-13, defines the term "treating" as refer[ing] to a method of reducing or delaying one or more symptoms of a Flavivirus infection. Thus in the disclosed method, treatment can refer to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity or progression of one or more symptoms of the disease or condition. For example, a method for treating a disease is considered to be a treatment if there is a 10% reduction in one or more symptoms or signs of the Fla vi virus infection in a subject as compared to a control. Thus, we interpret the term "treating" in claim 1, consistent with the Specification and the Examiner's claim interpretation, to include reducing or delaying one or more symptoms of a Flavivirus infection. Ans. 4. Carson discloses that movement disorders, and tremor occurred in 20% of West Nile Virus patients. P. 728, cols. 1 and 2. "Movement disorders have been frequently reported for patients with WNV [West Nile Virus] infection." P. 728, col. 2. West Nile Virus studies also "describe bradykinesia, rigidity, postural instability, and other features that are consistent with parkinsonism." P. 728, col. 2. Therefore, Carson evidences that movement disorders are symptoms of West Nile Virus. Pahwa discloses medications that reduce motor fluctuations and dyskinesia. Abstract. In particular, Pahwa generally discloses PD [Parkinson's disease] is a progressive neurodegenerative disorder with cardinal motor features of tremor, bradykinesia, and rigidity. Although initially effective, dopaminergic therapies are eventually complicated by motor 9 Appeal2018-006480 Application 14/437,434 fluctuations, including off time (periods of return of PD symptoms when medication effect wears off) and dyskinesia ( drug-induced involuntary movements including chorea and dystonia) in most patients. These motor complications can impair quality of life and cause significant disability. P. 9 84, col. 1, italicized emphasis added. Pahwa discloses that Tolcapone 100 mg TID decreased off time 32% (2.3 hours), tolcapone 200 mg TID decreased off time 48% (3.2 hours), and placebo decreased off time 20% (1.4 hours) (p < 0.01 for the tolcapone 200 mg TID group). At both tolcapone doses, a significant improvement in investigator global score occurred, as well as a significant decrease in levodopa dose (:S 200 mg) and number of levodopa doses per day ( decreased by approximately one). P. 989, col. 1; see also P. 984, col. 1 (indicting that "off time" is associated with motor fluctuations). Therefore, it was known to those of ordinary skill in the art at the time of the invention that tolcapone, a COMT inhibitor, could reduce symptoms associated with time off of Parkinson medications, including motor fluctuation symptoms. Because movement disorders and parkinsonism symptoms are also associated with West Nile Virus, it would have been obvious to one of ordinary skill in the art to select a movement disorder treatment drug, such as tolcapone, to treat movement disorders associated with West Nile Virus. Appellants argue that, "[ n Jone of the cited references disclose or suggest a method of treating a Flavivirus infection in a subject comprising administering to the subject a therapeutically effective amount of the recited compounds ( e.g., tolcapone) or a pharmaceutically acceptable salt thereof, wherein the compound inhibits a Flavivirus protease." App. Br. 8. However, we agree with the Examiner that, "[t]he recitation 'wherein the 10 Appeal2018-006480 Application 14/437,434 compound inhibits a Flavivirus protease' is a latent property of the compound [tolcapone] when administered to a subject infected with a Flavivirus, including WNV." Final Act. 5. "Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention." In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (citing In re Prindle, 297 F.2d 251, 254 (CCPA 1962)). The motivation to combine references does not have to be identical to the applicants to establish obviousness. In re Kemps, 97 F.3d 1427, 1430, 40 USPQ2d 1309, 1311 (Fed. Cir. 1996). "It is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable." In re Woodruff, 919 F.2d 1575, 1578, 16 USPQ2d 1934, 1936 (Fed. Cir. 1990). Because it was well known to those of ordinary skill in the art at the time of the invention to administer tolcapone for the treatment of movement disorders and parkinsonism generally, which are also symptoms of West Nile Virus, the claimed treatment method/process is an old process known in the art. Claiming the new benefit, that the tolcapone product also inhibits Flavivirus protease, cannot render the known process patentable again. "From the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing." In re Papesch, 315 F.2d 381, 391, 137 USPQ 43, 51 (CCP A 1963). Therefore, the administration of tolcapone to a West Nile Virus patient with a movement disorder or parkinsonism symptoms meets the claim. 11 Appeal2018-006480 Application 14/437,434 Rejection 2 Claims 1, 8, 14-15 We affirm the Examiner's rejection of claims 1, 8, and 14-16. The Examiner concludes that, "[i]t would have been obvious at the time the invention was made to administer tolcapone in combination with the compounds of Padmanabhan et al. to treat a subject having WNV infection." Final Act. 7. Appellants argue that, "Pahwa, Factor, Carson, and Padmanabhan fail to disclose or suggest using tolcapone to inhibit a Flavivirus protease." App. Br. 11. ANALYSIS Claims 1, 8, 14 and 15 The basis for affirming the rejection of claims 1, 8, 14, and 15 is essentially the same as for rejection 1. Pahwa, Factor, Carson treat a symptom of West Nile virus, and Padmanabhan treats or ameliorates Flavivirus infection. Abstract. This type of motivation has been recognized often by the predecessor of our reviewing court, which has held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the same purpose. In re Susi, 440 F.2d 442,445 (CCPA 1971); In re Crockett, 279 F.2d 274, 276-77 (CCPA 1960). The idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F .2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). The rejection of claims 14-15 is affirmed. 12 Appeal2018-006480 Application 14/437,434 Claims 16, 24-26 Claims 16 and 24--26 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Pahwa as evidenced by Factor in view of Carson and Padmanabhan. The Examiner adds Padmanabhan to rejection 1 as the foundation for rejection 2. The Examiner finds that Padmanabhan et al. teach methods of treating a Flavivirus infection in a subject by administering a therapeutically effective amount of novel Flavivirus inhibitor, specifically Flavivirus serine protease inhibitors for the treatment of West Nile Virus infection (p.8, lines 25-29). Padmanabhan et al. teach administering the compound of claim 1 to a subject having a Flavivirus infection ( claim 1 ), wherein the Flavivirus infection includes West Nile Virus. Padmanabhan et al. teach the compounds were effective in vitro (p.46-48, Example 1 ). Final Act. 7. The Examiner concludes that, "[i]t would have been obvious at the time the invention was made to administer tolcapone in combination with the compounds of Padmanabhan et al. to treat a subject having WNV infection." Final Act. 7. Appellants argue that, "Pahwa, Factor, Carson, and Padmanabhan fail to disclose or suggest using tolcapone to inhibit a Flavivirus protease." App. Br. 11. ANALYSIS While at first it may seem inapposite based on our conclusion with respect to rejection 1, we do not find that the Examiner has provided evidence to support a prima facie case that the elected species, tolcapone, inhibits a Flavivirus protease, as claimed. Unlike claim 1, claim 16 is 13 Appeal2018-006480 Application 14/437,434 directed to a method of inhibiting a Flavivirus protease in a cell, comprising: contacting a cell with an effective amount of a tolcapone compound or a pharmaceutically acceptable salt thereof. We find that the preamble claim language, "a method of inhibiting a Flavivirus protease in a cell," is necessary to give life and meaning to the claim. Seachange International, Inc. v. C-Cor Inc. (Fed. Cir. 2005) (preamble a limitation where it provides antecedent basis for terms in the claim body). The preamble of claim 16 provides antecedent basis for the effective amount of tolcapone compound claimed (effective amount to inhibit Flavivirus protease in a cell.) Unlike rejection 1, we do not find that the Examiner has provided a legally sufficient rationale, motivation or reason to combine the cited references to reject claim 16. Padmanabhan discloses that Flavivirus protease inhibitors other than tolcapone were known to those of ordinary skill in the art, and that they were known to treat Flavivirus infection. Padmanabhan, p. 8. The Examiner does not point to any specific compound in Padmanabhan having the structure of tolcapone that functions as a Flavivirus protease inhibitor. The Examiner argues that Pahwa, Factor, and Carson, disclose the administration of tolcapone in an effective amount to treat movement disorders and parkinsonism, including movement disorders common to patients having West Nile Virus. However, the Examiner has not provided persuasive evidence that the ordinary artisan would have expected that tolcapone would function as a Flavivirus protease inhibitor, as required by claim 16. The Examiner argues that, "[t]he skilled artisan would have been motivated to administer the combination of tolcapone with the antiviral compounds of Padmanabhan et al. because the combination would have 14 Appeal2018-006480 Application 14/437,434 been expected to treat both the WNV infection and the Parkinsonism symptom of WNV infection." Final Act. 8. What is missing from the Examiner's analysis is why one of ordinary skill in the art, desiring to inhibit a Flavivirus protease, would have combined Padmanabhan, disclosing Flavivirus protease inhibitors (not indicated by the Examiner to include the elected species of Flavivirus protease inhibitor, tolcapone ), with three references disclosing the treatment of movement disorders (a symptom of Flavivirus infection). The Examiner cannot rely on the inherent protease-inhibiting properties of tolcapone here without a sufficient reason to administer tolcapone in the first place. Nor can the Examiner rely on obviousness without a motivation to combine the cited references, or a nexus between the references that evidences that tolcapone functions as a Flavivirus protease inhibitor, as required by claim 16. In other words, claim 16 requires that the elected species, tolcapone, function as a Flavivirus protease inhibitor (not just that tolcapone treat a symptom of Flavivirus infection). We do not find the Examiner's rationale that the cited references each treat Flavivirus infection or its symptoms, to be a legally sufficient rationale for selecting tolcapone, a known movement disorder drug, and combining it with a Flavivirus protease inhibitor (not the elected species), to meet the claim requirement that tolcapone is a Flavivirus protease inhibitor. The rejection of claims 16, and 24-26 is reversed. 15 Appeal2018-006480 Application 14/437,434 CONCLUSION OF LAW The cited references support the Examiner's obviousness rejection 1, which is affirmed for the reasons of record. The rejection of claims 14 and 15 is also affirmed. The rejection of claims 16, and 24-26 is reversed. We limit this Decsision to the single issue of the elected species and take no position respecting the patentability of the broader generic claims, including the remaining, non-elected species. 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 )(iv). AFFIRMED-IN-PART 16 Copy with citationCopy as parenthetical citation