Detailed Action
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 .1
Status of Claims
Claims 1-9 are pending. Claims 1-3 and 5-7 are under examination. Claims 4 and 8-9 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of the species in the reply filed on Feb 27 2026 is acknowledged.
NITD609 aka Cipargamin or KAE609, for claim 1 (drug)2
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116
220
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primaquine for claim 5 (additional antimalarial compound)
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)). Note claims 1-3 and 5-7 are under examination. Claims 4 and 8-9 are withdrawn as being directed to non-elected species. Claim 4 is noted to be withdrawn from examination as it claims non-elected species additional antimalarial compound, TD6450, administered along with elected species, NITD609.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 14 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609 The Journal of Infectious Diseases, Volume 213, Issue 1, 1 January 2016, Pages 100–104. Zhang is cited on the IDS, filed 14 2023, as NPL ref no. 3.
Claim 1 is a method of blocking transmission of a Plasmodium parasite by an infected subject comprising
administering to the subject a therapeutically effective amount of a drug that increases rigidity of iRBCs selected from the group consisting of TD-6450, NITD609, and L-THP.
Regarding claim 1, Zhang teaches the rapid disappearance of circulating Plasmodium vivax and Plasmodium falciparum in KAE609 (aka NITD609) treated patients with malaria. See Figure 1, page 101. Zhang teaches this was due to significant changes in the morphological and rheological properties of the infect red blood cells. Id. Zhang teaches that ring-stage, parasite-infected RBCs exposed to KAE 609 become spherical and rigid. See Abstract. See also Results Section, page 102.
Zhang teaches:
The increase in sphericity is associated with a decrease in the deformability (increase in rigidity) of the RBCs (infected or uninfected). . . (See Figure 1C) . . . We then ascertained whether the demonstrable increase in the sphericity and rigidity of the parasite-infected RBCs subsequent to exposure to KAE609 were sufficient to result in their retention (and subsequent clearance) in the spleen. See Results Section, page 102.
Regarding claims 2 and 3 and the limitations of Plasmodium falciparum and Plasmodium vivax, Zhang teaches the subjects were infected with Plasmodium vivax and Plasmodium falciparum. See Figure 1, page 101.
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.
Claims 1-3 and 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609 The Journal of Infectious Diseases, Volume 213, Issue 1, 1 January 2016, Pages 100–104 in view of Ashley et al. Primaquine: the risks and the benefits Malaria Journal 2014, 13:418. Ashley is cited by the Examiner on the PTO-892 form.
The method of claims 1-3 are taught by Zhang as follows.
Regarding claim 1, Zhang teaches the rapid disappearance of circulating Plasmodium vivax and Plasmodium falciparum in KAE609 (aka NITD609) treated patients with malaria. See Figure 1, page 101. Zhang teaches this was due to significant changes in the morphological and rheological properties of the infect red blood cells. Id. Zhang teaches that ring-stage parasite-infected RBCs exposed to KAE 609 become spherical and rigid. See Abstract. See also Results Section, page 102. Zhang teaches:
The increase in sphericity is associated with a decrease in the deformability (increase in rigidity) of the RBCs (infected or uninfected). . . (See Figure 1C) . . . We then ascertained whether the demonstrable increase in the sphericity and rigidity of the parasite-infected RBCs subsequent to exposure to KAE609 were sufficient to result in their retention (and subsequent clearance) in the spleen. See Results Section, page 102.
Regarding claims 2 and 3 and the limitations of Plasmodium falciparum and Plasmodium vivax, Zhang teaches the subjects were infected with Plasmodium vivax and Plasmodium falciparum. See Figure 1, page 101.
While Zhang teaches and renders obvious the claimed method of 1-3 as detailed above, it does not teach the species of claims 1-4 and in particular, claims 5-7, where at least one additional antimalarial compound, (aka a conventional curative treatment such as elected species primaquine) is co-administered with NITD609 (aka KAE609). It is noted that Zhang recognizes other anti-malarial treatments, see page 104, column 1. Zhang suggests the effectiveness of a “dual killing mechanism” unique to KAE609, which includes not only direct killing of the parasite but also through biochemical disruption of infected red blood cells (RBCs). Id. Zhang references another known conventional curative malaria treatment, artesunate, known for its sole malaria killing activity, not any known rheological/shape changing property of RBCs. Id.
To address this, Ashley teaches the advantages of treating malaria parasite infections where it states:
Primaquine is the only generally available anti-malarial that prevents relapse in vivax and ovale malaria, and the only potent gametocytocide in falciparum malaria. Primaquine becomes increasingly important as malaria-endemic countries move towards elimination. . . . See Abstract.
As both Zhang and Ashley teach the treatment of malaria, it is prima facie obvious to combine the teachings of the two per MPEP 2144.06, I. Combining Equivalents Known for the Same Purpose.3
Prior to the filing of the instant application a PHOSITA following the teachings of Zhang to treat malaria with NTID609 (Plasmodium vivax and Plasmodium falciparum) would have found it prima facie obvious to combine it with the teachings of Ashley to treat malaria (both the vivax and falciparum parasites) with primaquine to predictably arrive at the claimed invention. Per MPEP 2143 (a), the rationale to do so is the combination of prior art elements according to known methods to yield predictable results, (combining two anti-malarial drugs treat malaria), which per MPEP2144.05, is prima facie obvious.
Conclusion and Correspondence
In summary no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a 371 of PCT/EP2021/085497 12/13/2021
FOREIGN APPLICATIONS
EP 20306560.2 12/14/2020
2 CAS No. 1193314-23-6
((1R,3S)-5', 7-Dichloro-6-fluoro-3-methyl-spiro[2,3,4,9-tetrahydropyrido[3,4-b ]indole-1,3 '-indoline]-2' -one)
3 "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 to be used for the very same purpose.... [T]he 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) (citations omitted)
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