Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application, filed 01/23/2024 is a National Stage entry of PCT/US2022/074071, International Filing Date: 07/22/2022. PCT/US2022/074071 claims foreign priority to 1-2021-04540, filed 07/23/2021. A certified copy of the foreign priority application is of record; however, it is not in the English language, and an English translation of the foreign priority application is not on file. Therefore, the effective filing and priority date of the claims currently is 7/22/2022. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Status of Claims
Claims 1-2, 4, 9-10, 12, 16-18, 20, 24, 26-27, 29, 33, 35, 37, 39, 44, and 46 are pending as of the response filed on 6/18/26. Claims 3, 5-8, 11, 13-15, 19, 21-23, 25, 28, 30-32, 34, 36, 38, 40-43, 45, and 47-52 have been canceled.
Applicant’s election of invention II, claims 1-2, 4, 9-10, 12, 16, 39, 44, and 46 in the reply filed on 6/18/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 17-18, 20, 24, 26-27, 29, 33, 35, and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/18/26.
Claims 1-2, 4, 9-10, 12, 16, 39, 44, and 46 were examined and are rejected.
Claim Rejections-35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chien et. al., J. Experimental Medicine, vol. 218(10), e20210724, publ. 8/26/2021.
This rejection is made as Applicants have not perfected foreign priority, and currently the effective filing and priority date of the claims is 7/22/2022.
Chien discloses treatment of patients with uncomplicated P. falciparum malaria by administering a combination of 40 mg. dihydroartemisinin, 320 mg. piperaquine, and 400 mg imatinib per day for a period of three days, and that this therapy caused no significant adverse events (abstract; p. 2 of 8, left col., beginning with 2nd para-right col., top 3 lines; p. 3 of 8, Table 1). Chien further discloses the combination therapy results in faster resolution of pyrexia and decrease in parasite density (p. 4 of 8, left col., 2nd para). Chien therefore anticipates the claim.
Claim Rejections-35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 4, 9-10, 12, 39, 44, and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Low et. al., WO 2014100113 A2, publ. 6/26/2014.
Low et. al. teaches administration of a therapeutically effective amount of a Syk kinase inhibitor for treating malaria (title & abstract; para [0001], [0015-0018]). Low teaches exemplary Syk kinase inhibitors to include Syk kinase inhibitor II, Syk kinase inhibitor IV, imatinib mesylate, piceatannol, R406, and R788, among others (para [0024-0025]). Low teaches the Syk kinase inhibitor as optionally in the form of a pharmaceutically acceptable salt (para [0017]); therefore, it would have been understood by a person of ordinary skill in the art to include imatinib freebase as well as imatinib mesylate as a Syk kinase inhibitor for the treatment of malaria. Low teaches Syk kinase inhibitor therapy offers distinct advantages as it involves inhibition of a red blood cell tyrosine kinase that has no counterpart in the parasite genome, making the development of drug resistance less likely (para [0033]). Low teaches an embodiment wherein the Syk kinase inhibitor is administered in combination with one or more antimalarial drugs, with artemisinin, dihydroartemisinin, chloroquine, quinine, proguanil, lumefantrine, artemether, amodiaquine, pyrimethamine, mefloquine, sulfadoxine, and indolone N-oxides taught as exemplary (para [0026], [00234], [00276], [0283]). Low acknowledges WHO suggests combination treatments as a strategy to combat drug resistance (para [0004]). Additionally, Low teaches the specific combination of mefloquine and artesunate as the additional antimalarial agents to be administered in combination with a Syk kinase inhibitor (para [00283]). Treatment encompasses both uncomplicated as well as severe malaria; additionally, high fever is a characteristic of malaria, as well as chills, flu-like symptoms, and anemia (para [0084]). Low teaches an effective concentration of Syk kinase inhibitor to range from about 100 to about 2000 mg/day (para [00112]). Low teaches an embodiment wherein imatinib mesylate as a Syk kinase inhibitor for treatment is administered from about 200-1200 mg/day (para [00154]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have treated severe or uncomplicated malaria in a subject in need thereof comprising administering a therapeutically effective amount of an isoform of artemisinin selected from artemisinin, artesunate, or artemether; a hydrophobic amine such as chloroquine, lumefantrine, mefloquine, amodiaquine, sulfadoxine in combination with pyrimethamine; and a Syk kinase inhibitor such as Syk kinase inhibitor II, Syk kinase inhibitor IV, imatinib mesylate, piceatannol, R406, and R788, in consideration of the teachings of Low. Low teaches treatment of malaria, including uncomplicated and severe malaria by administering an effective amount of a Syk kinase inhibitor, and further teaches combination of a Syk kinase inhibitor with one or more additional anti-malarial agents, with all of the aforementioned agents included for treatment. Furthermore, Low teaches an embodiment wherein a Syk kinase inhibitor is combined with anti-malarials, with antimalarials taught to specifically include the combination of mefloquine and artesunate. As such, one of ordinary skill in the art would have been motivated to have combined a Syk kinase inhibitor with a hydrophobic amine and an artemisinin isoform, particularly as combination therapy is taught as a strategy to overcome drug resistance.
Regarding the recitation in claims 1 and 9, “in amounts effective to eliminate parasitemia within about 72 hours”, Low teaches administering a therapeutically effective amount of a Syk kinase inhibitor, and it would have further been obvious that the additional anti-malarials would have been administered in therapeutically effective amounts for treatment. Thus, the therapeutically effective amounts of Syk kinase inhibitor, hydrophobic amine, and isoform of artemisinin would have met “in amounts effective to eliminate parasitemia within about 72 hours” in the absence of evidence to the contrary. Additionally, regarding “a subject suffering from pyrexia associated with the malaria experiences a monotonous decline in body temperature and does not experience a second increase in temperature during at least one day of therapy”, as Low teaches the claimed combination treatment for malaria, it would have been prima facie obvious the result of treatment would have provided this result.
Regarding instant claims 39 and 46, “the pyrexia is resolved faster relative to a standard-of-care (SOC) cohort….”, as Low teaches the combination therapy recited by the instant claims for the treatment of malaria, it would have been prima facie obvious the effect of treatment would have been the same as claimed, i.e., meeting the treatment result recited in these claims.
Regarding instant claim 44, “a response to therapy is bimodal…”, as Low teaches the combination therapy recited by the instant claims for the treatment of malaria, it would have been prima facie obvious the effect of treatment would have been the same as claimed, i.e., meeting the treatment result recited in claim 44.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Low et. al., WO 2014100113 A2, publ. 6/26/2014, in view of Myint et. al., Transactions of the Royal Soc. Trop. Med. & Hygiene, vol. 101, pp. 858-866, publ. 2007.
Low et. al. teaches administration of a therapeutically effective amount of a Syk kinase inhibitor for treating malaria (title & abstract; para [0001], [0015-0018]). Low teaches exemplary Syk kinase inhibitors to include Syk kinase inhibitor II, Syk kinase inhibitor IV, imatinib mesylate, piceatannol, R406, and R788, among others (para [0024-0025]). Low teaches the Syk kinase inhibitor as optionally in the form of a pharmaceutically acceptable salt (para [0017]); therefore, it would have been understood by a person of ordinary skill in the art to include imatinib freebase as well as imatinib mesylate as a Syk kinase inhibitor for the treatment of malaria. Low teaches Syk kinase inhibitor therapy offers distinct advantages as it involves inhibition of a red blood cell tyrosine kinase that has no counterpart in the parasite genome, making the development of drug resistance less likely (para [0033]). Low teaches an embodiment wherein the Syk kinase inhibitor is administered in combination with one or more antimalarial drugs (para [0026], [00234], [00276], [0283]). Low acknowledges WHO suggests combination treatments as a strategy to combat drug resistance (para [0004]). Low teaches an effective concentration of Syk kinase inhibitor to range from about 100 to about 2000 mg/day (para [00112]). Low teaches an embodiment wherein imatinib mesylate as a Syk kinase inhibitor for treatment is administered from about 200-1200 mg/day, especially about 400 mg/day (para [00154]).
Low doesn’t explicitly teach or suggest further administering the combination of dihydroartemisinin at 40 mg/day and piperaquine at 320 mg/day.
Myint teaches the combination of dihydroartemisinin (DHA) and piperaquine (PIP) as a fixed dose combination is an inexpensive, safe, and highly effective treatment for uncomplicated malaria (title & abstract). Myint teaches the dosing regimen has been simplified from four doses to once daily dosing over a period of 3 days, wherein the combination is administered orally in tablet form containing 40 mg. DHA and 320 mg. PIP (abstract; p. 859, left col., beginning with 2nd para-right col., top para).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claim to have arrived at the claimed method of treating uncomplicated malaria comprising administering the three-drug combination of the Syk kinase inhibitor, imatinib, at a dose of 400 mg/day; 40 mg./day DHA; and 320 mg. PIP, in consideration of the combined teachings of Low and Myint. Low teaches treatment of malaria, including uncomplicated by administering a Syk kinase inhibitor, of which imatinib and imatinib mesylate are exemplified. Low further includes a dose of 400 mg. of imatinib for treatment, and teaches combination with other antimalarials. Myint teaches a daily dose of the combination of 40 mg./day DHA and 320 mg. PIP as safe and highly effective for treating uncomplicated malaria. As Low teaches combination therapy as a means to combat the development of drug resistance, one of ordinary skill in the art would have arrived at the claimed combination therapy for treating a subject having uncomplicated malaria, and have had a reasonable expectation that the development of drug resistance would have been reduced.
Information Disclosure Statements
The IDS filed on 1/23/24 and 2/26/26 have been considered.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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