Ex Parte Kubata et alDownload PDFPatent Trial and Appeal BoardMar 16, 201813999318 (P.T.A.B. Mar. 16, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/999,318 02/04/2014 7590 Nash & Titus, LLC 21402 Unison Road Middleburg, VA 20117 03/16/2018 FIRST NAMED INVENTOR Bruno K. Kubata 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. Army 183B 1213 EXAMINER DA VIS, DEBORAH A ART UNIT PAPER NUMBER 1655 MAILDATE DELIVERY MODE 03/16/2018 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 BRUNO K. KUBAT A, SAMUEL K. MARTIN, and WILBUR K. MILHOUS Appeal2017-005280 Application 13/999,318 Technology Center 1600 Before JEFFREY N. FREDMAN, TA WEN CHANG, and DAVID COTTA, 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 treating kinetoplastid infections. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. Statement of the Case Background "Trypanosoma species pathogenic to human beings and domestic animals in Africa, cause one of the world's most neglected tropical 1 Appellants identify the real party in interest as the U.S. Government as represented by the Secretary of the Army (see App. Br. 2). Appeal2017-005280 Application 13/999 ,318 infections - African trypanosomiasis" (Spec. 1: 18-20). "Treatment of infected persons with the few available synthetic trypanocidal agents have shown significant drawbacks related to high cost, host toxicity, limited oral bioavailability, and a requirement for hospitalization during the entire course of treatment" (Spec. 3:20-23). "[T]he Chinese plant Artemesia annua has been used to treat malaria for centuries" (Spec. 5: 1 ). "Artemisinins have never before been used to treat human and veterinary trypanosomiasis. Until now, no experimental study has been carried out to establish the effectiveness of artemisinin or its derivatives on any Trypanosoma species" (Spec. 5: 14--17). The Claims Claims 1, 5-7, 9, and 13 are on appeal. Claim 1 is representative and reads as follows: 1. A method of treating kinetoplastid infections comprising: (a) diagnosing a kinetoplastid infection in a mammal; and (b) administering to said mammal a pharmaceutical composition wherein said composition contains a pharmaceutical dose of C1sH220s with a molecular weight of 282, sufficient to decrease said kinetoplastid infection. The Issue The Examiner rejected claims 1, 5-7, 9, and 13 under 35 U.S.C. § 103(a) as obvious over Yang2 and PubChem3 (Final Act. 2--4). 2 Yang et al., Effects of qinghaosu (artemisinin) and its derivatives on experimental cutaneous leishmaniasis, 106 PARASITOLOGY 7-11 (1993). 3 PubChem, Artemisinin, http://pubchem.ncbi.nlm.nih.gov/compound/ artemisinin 1-19 (CID 68827, accessed Nov. 14, 2015). 2 Appeal2017-005280 Application 13/999 ,318 The Examiner finds Yang "teaches artemisinin is capable of inducing the killing of intracellular parasitic amastigotes in murine macrophages" (Final Act. 2). The Examiner finds Yang teaches "artemisinin can kill the parasites in cell-free cultures" (id. at 3) and that artemisinin derivatives treated Leishmania infected mice (id. at 2). The Examiner finds Yang teaches artemisinin is "a useful therapeutic agent in the treatment of clinical leishmaniasis, which reads on kinetoplastid infection" (id. at 3). The Examiner finds it obvious "to diagnose kinetoplastid infection" and that "one skilled in the art would have reasonably understood that if artemisinin was effective in killing leishmanial parasites in mice, then such treatment can be extrapolated to a human" (Final Act. 3--4). The issue with respect to this rejection is: Does the evidence of record support the Examiner's conclusion that Yang and PubChem render obvious the diagnosis and treatment of kinetoplastid infections in mammals with artemisinin as required by claim 1? Findings of Fact 1. Yang teaches that "artemisinin is the principal component in the anti-malarial effect of the traditional Chinese herb Artemisia annua" and "may have broad anti-parasitic potential" (Yang 7, col. 1 ). 2. Yang teaches "L. major promastigotes were cultured for 48 h in vitro in the presence of graded doses of artemisinin or in medium containing the diluent Me2SO. The viability of the parasites decreased progressively with increasing concentrations of artemisinin and no viable parasites were detectable at around 10-5 M" (Yang 8, col. 2). 3 Appeal2017-005280 Application 13/999 ,318 3. Yang teaches "[ m ]urine peritoneal macrophages were infected with L. major promastigotes for 24 h and then cultured for 48 h with various concentrations of artemisinin or artemether and the viable amastigotes estimated. Both artemisinin and artemether are capable of inducing the killing of the intracellular parasites" but "[ u ]ninfected macrophages cultured with the highest concentrations of the compounds used (1·23 x 10-4 M) for the same period remained viable" (Yang 9, col. 1-2). 4. Yang teaches "[ m ]ice infected in the footpad and injected intramuscularly in the thigh with artemether in oil developed significantly smaller lesions compared to controls injected with oil alone" (Yang 8, col. 2). 5. Yang teaches "[ m ]ice receiving orally 200 mg/kg/ day of artemether developed significantly smaller lesions compared to those receiving oil alone or the untreated controls ... Mice receiving either 200 or 50 mg/kg/day of artemether had significantly lower parasite loads compared to the controls" (Yang 9, col. 1 ). 6. Yang teaches that "[a ]rtemisinin and its derivatives ... have a leishmanicidal effect in vitro and, importantly, in vivo. These compounds appear to exert their effect directly on the leishmanial parasite, since they can kill the parasites in cell-free cultures" (Yang 9, col. 1-2). 7. Yang teaches "this series of compounds could be potentially useful therapeutic agents in the treatment of clinical leishmaniasis" (Yang 9, col. 2). 8. PubChem teaches the molecular formula of artemisinin is C1sH220s and the molecular weight is 282 (PubChem 1 ). 4 Appeal2017-005280 Application 13/999 ,318 9. Original claim 7 teaches the "kinetoplastid infections are selected from Leishmania infection and trypanosome infection" (Spec. 25:21-22). Principles of Law When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103. KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). Analysis We adopt the Examiner's findings of fact and reasoning regarding the scope and content of the prior art (Final Act. 2--4; FF 1-9) and agree that the claims are obvious over Yang and PubChem. We address Appellants' arguments below. Appellants contend Not all artemisinins show antiplasmodial or anti-tumoricidal activity. The artemisinins in Yang et al. are chemically different than those of the present invention due to their mode of extraction. Artemether has a chemical formula of C16H260s and a MW of 298. Artesunate has a chemical formula of C19H 2sOs and a MW of 384. Therefore, it cannot be said that the artemisinin C1sH220 with a MW of 282 is obvious from Yang et al. for in vivo treatment of lieshmaniasis. Yang, et al. did not take the extra step to test artemisinin in vivo in mammals. (App. Br. 4). 5 Appeal2017-005280 Application 13/999 ,318 We find this argument unpersuasive because Yang expressly teaches that artemisinin - which PubChem discloses has the formula C15H220 and MW of 282 (FF 8)- has anti-parasitic potential (FF 1 ), kills Leishmania major organisms in vitro (FF 2) and in cell culture without killing macrophages (FF 3). Yang teaches that a derivative of artemisinin, artemether, kills Leishmania major organisms in mouse footpads by intramuscular or oral routes (FF 4--5). Yang concludes that artemisinin and its derivatives treat Leishmania major organisms and may be "useful therapeutic agents in the treatment of clinical leishmaniasis" (FF 6-7). Based on these teachings of Yang, we agree with the Examiner that the ordinary artisan would have found it obvious to try artemisinin as a therapeutic for clinical leishmaniasis with a reasonable expectation of success, given that the artemisinin kills Leishmania major organisms without killing host cells (FF 2-3). Our reviewing court found that in vitro testing of compounds as therapeutic agents was sufficient to demonstrate the usefulness of the compounds for an in vivo human setting. See In re Brana, 51F.3d1560, 1566 (Fed. Cir. 1995). Here, where Yang provides direct evidence of in vitro functionality for artemisinin in treatment of leishmaniasis and directly suggests clinical treatment where artemisinin is one of three tested compounds, the person of ordinary skill has good reason to pursue this known option for leishmaniasis treatment that is within their technical grasp. See KSR, 550 U.S. at 421. Appellants contend: "One of ordinary skill in the art would have known that not all extracts from Artemisia annua result in useful treatments. 6 Appeal2017-005280 Application 13/999 ,318 See figures 2 and 3 of the present specification where many derivatives are provided but only a few showed anti-lieshmaniasis ability" (App. Br. 4). We find this argument unpersuasive because Yang specifically shows that artemisinin shows anti-lieshmaniasis ability in vitro (FF 2) without killing host cells (FF 3), directly demonstrating a reasonable expectation of success. "'Obviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success." In re Kubin, 561F.3d1351, 1360 (Fed. Cir. 2009) (citation and alterations omitted). Appellants contend "the Examiner has not pointed to any evidence of the Appellant's pharmaceutical composition and method was even tested by Yang, et al. To the contrary, Yang, et al. is directed to the treatment of leishmaniasis with the qinghaosu (artemisin) derivatives of artemether and artesunate" (Reply Br. 2). We find this argument unpersuasive because Yang expressly teaches treatment in vitro of L. major promastigotes with artemisinin (FF 2) as well as the artemether derivative (FF 3 ). Yang's use of the phrase "various concentrations of artemisinin or artemether" demonstrates that both compounds were tested in cell culture (FF 3). While we agree with Appellants that Yang did not exemplify testing in mouse footpads with artemisinin itself, only testing with the artemether derivative (FF 4--5), we agree with the Examiner's finding that it would have been obvious to use artemisinin itself as the therapeutic agent because artemisinin kills L. major promastigotes in vitro and in cell culture (FF 2-3) and Yang generally suggests "this series of compounds could be potentially useful therapeutic agents in the treatment of clinical leishmaniasis" (FF 7). These teachings 7 Appeal2017-005280 Application 13/999 ,318 reasonably render it obvious to try artemisinin in the treatment of clinical leishmaniasis and the in vitro data provides a reasonable expectation of success for such clinical treatment. Conclusion of Law The evidence of record supports the Examiner's conclusion that Yang and PubChem render obvious the diagnosis and treatment of kinetoplastid infections in mammals with artemisinin as required by claim 1. SUMMARY In summary, we affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as obvious over Yang and PubChem. Claims 5-7, 9, and 13 fall with claim 1. 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 8 Copy with citationCopy as parenthetical citation