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. Priority Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119( a ) -(d) and (f) or under 35 U.S .C. 120, 121, 365(a) or (b), or 386(a) is acknowledged. The present application is drawn fro m PCT/EP2022/056603, filed 3/15/2022; and claims benefit under 35 U.S.C. (119(a)-(d) to foreign application EP21163132.0, filed 3/17/2021. R eceipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Status of Claims Claim s 1-13 are pending and a re being examined on the merits. Claim Objections Claims 7-8 and 12 are objected to because of the following informalities: The claims recite “anti-CD3”. It is interpreted that the phrase anti-CD3 is referring to an anti-CD3 antibody . Applicants should reference an “anti-CD3 antibody ” in claims 7-8 and 12 as they did in claims 10 and 13. Appropriate correction is required. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b ) CONCLUSION.— The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. Claim s FILLIN "Enter claim indentification information" \* MERGEFORMAT 1- 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 1-13 are rejected under 35 U.S.C. 112(b), because each of the claims are a “use” claim. According to MPEP 2173.05(q), “[a] ttempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which reads: ‘[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon’ was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich , 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).” Claims 1-13 recite a method of using cytokine-induced killer (CIK) cells for treatment of diseases caused by a Plasmodium infection ; however the claim does not recite any active, positive steps defining how this use is actually practiced and is therefore rejected under 35 U.S.C. 112(b). That is, the claims are not drawn to a “ method for treating a disease caused by Plasmodium infection to a patient in need thereof, wherein the method comprises administering CIK cells to the subject.” Instead, the claims are drawn to the “use of” CIK cells for treating without any active steps for how the use is practiced. As all the claims (1-13) recite the “use”, without active method steps for treatment, claims 1-13 are rejected for indefiniteness. Claim 7 recites wherein the PBCs have been treated with IFN-γ, IL-1β, IL-2 and anti-CD3, in that order . However, it is not clear what parameters define administering the cytokines and antibody treatments so as to be “in that order”. That is, claim 8, which depends from claim 7, further limits the order such that IFN-γ is applied on day 1, while the IL-1β, IL-2 and anti-CD3 antibody are applied on day 2. Even in claim 8, it is unclear what order the IL-1β, IL-2 and anti-CD3 antibody agents of “day 2” are presented. It is unclear if a minimum amount of time is required between presenting, for example, IL-1β and the anti-CD3 antibody; is 5 minutes sufficient, or > than 1 hour, or does simultaneous administration of IL-1β, IL-2 and anti-CD3 antibody qualify as applying them “in that order” as long as they are applied after the IFN-γ of day 1? The specifications do not describe or define the parameters of “in that order”. Thus, it is unclear what the limitation of “in that order” encompasses with respect to the precise timing of which agents are applied to the cells. As the metes and bounds of the claim are unclear, claim 7 is rejected for indefiniteness. Claim 13 recites “ about 1000 IU/mL human recombinant IFN-γ; about 50 ng/mL anti-CD3 antibody; about 100 IU/mL IL-1β; and about 600 IU/mL IL-2”. The specifications do not define the term “about”, specifically in reference to the range around the cited concentrations which are encompassed by “about”. That is, it is unclear if the respective concentrations of each agent, of claim 13, even further limit the range of concentrations recited for each agent in claim 10, from which claim 13 depends, as the term “about” allows some deviation from the cited concentration, but does not define how much deviation is encompassed. As the term “about” is not defined in the specifications, and it is unclear what range of concentrations are encompassed by the term “about”, thus the concentration limitations of claim 13 are indefinite. As the metes and bounds of the claim are unclear, claim 13 is rejected for indefiniteness. 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims FILLIN "Insert the claim numbers which are under rejection." \d "[ 1 ]" 1-3 and 5-6 are rejected under 35 U.S.C. 102 FILLIN "Insert either \“(a)(1)\” or \“(a)(2)\” or both. If paragraph (a)(2) of 35 U.S.C. 102 is applicable, use form paragraph 7.15.01.aia, 7.15.02.aia or 7.15.03.aia where applicable." \d "[ 2 ]" (a)(1) and (a)(2) as being FILLIN "Insert either—clearly anticipated—or—anticipated—with an explanation at the end of the paragraph." \d "[ 3 ]" anticipated by FILLIN "Insert the prior art relied upon." \d "[ 4 ]" Xia et al., (US 2008/0213895; published 11/4/2008) . Xia teaches the mass production of dendritic cells and cytokine induced killer cells as a preparation of a vaccine, used to improve the symptoms of infectious diseases (abstract). Xia teaches a method for growing and proliferating highly purified tumor cells to derive cellular activators (Koyo) for activating dendritic cells or D-cytokine induced killer cells (D-CIK) from umbilical cord blood or peripheral blood, wherein the activated cells are infused back into the patents for medical treatments (pg. 1, para. 0003). Xia teaches CIK cells are CD3+/CD56+, and also known as the natural killer (NK) cells (pg. 2, para. 0013), and that the D-CIK cells of the invention are DC stimulated CIK cells (pg. 2, para. 0014). Xia teaches the D-CIK cells can be used to fabricate a vaccine in which the D-CIK cells are infused back in to the patient (pg. 2, para. 0021). Xia teaches the vaccine improves the symptoms of infections resulting from antigen, virus, bacteria, parasites or fungus (pg. 3, para. 0029). Regarding parasites, Xia teaches the vaccines for parasites selected from Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malaria, among others (pg. 3, para. 0032). Regard i ng the preparation of D-CIK cells, Xia teaches isolating mononuclear cells from the peripheral blood (pg. 5, para. 0073); whereby the isolated cells are cultured with an anti-CD3 monoclonal antibody, IL-2 and IL-1α, and whereby the culture medium is replaced every 2-3 days by adding fresh IL-2 culture medium (pg. 5, para. 0075). Regarding claims 1-3 ; the methods of Xia, comprising D-CIK cells, infused into a patient as a vaccine, for the treatment of parasite infections resulting from Plasmodium falciparum anticipate instant claims 1-2 . Regarding claim 3 , it is known that malaria tropica is caused by Plasmodium falciparum, and thus the methods of administering D-CIK cells for treating infections resulting from Plasmodium falciparum, of Xia, anticipate instant claim 3 . Regarding claims 5-6 ; Xia teaches the D-CIK cells are NK cells, which are CD3+/CD56+ (pg. 2, para. 0013), and thus the D-CIK cells of Xia anticipate instant claim 5 . Further, Xia teaches the D-CIK cells are treated NK cells which were derived from peripheral blood mononuclear cells (PMBCs; pg. 5, para. 0073). PMBCs are eukaryotic cells. Thus the D-CIK vaccines of Xia anticipate instant claim 6 . 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 . Claims FILLIN "Pluralize claim, if necessary, and then insert the claim number(s) which is/are under rejection." \d "[ 1 ]" 1-6 are rejected under 35 U.S.C. 103 as being obvious over FILLIN "Insert the prior art reference." \d "[ 2 ]" Xia et al., (US 2008/0213895; published 11/4/2008) as evidenced by Sinha et al., (Parasite, 2014, 21:61) . Xia et al. teaches D-CIK cells, provided as a vaccine for the treatment of parasite infections resulting from Plasmodium falciparum; and thus anticipates instant claims 1-3 and 5-6 , as described above. However, Xia does not teach wherein the patients receiving the vaccine treatment of the invention were resistant against known malaria medications (i.e., re. claim 4). Sinha et al. teaches the challenges of drug-resistant malaria (title). Sinha teaches that over the past six decades, the drug resistance of Plasmodium falciparum has become an issue of utmost concern, and the emphasizes futuristic approaches like nanotechnology and stem cell therapy that may impede resistant malaria (abstract). It would have been obvious to apply the methods of administering the D-CIK cell vaccine for treatment of malaria resulting from Plasmodium falciparum infections, of Xia et al., to patients that are resistant against known malaria medications. One would have been motivated to do so given that resistance to known malaria medications has been a prevalent issue for decades, impairing the efforts to find effective therapeutics for malaria, and that novel approaches are needed, as taught by Sinha et al. There would have been a reasonable expectation for success given that the D-CIK cell vaccines, of Xia et al., are a novel approach for treating Plasmodium falciparum infections that do not rely on known malaria medications for which patients have resistance. Regarding claim 4 ; it would have been obvious to administer the D-CIK cell vaccines for treatment of malaria resulting from Plasmodium falciparum infections, of Xia et al., to patients which are resistant to known malaria medications. Thus, the methods of Xia, as evidenced by Sinha, make obvious instant claim 4 . Claims FILLIN "Pluralize claim, if necessary, and then insert the claim number(s) which is/are under rejection." \d "[ 1 ]" 1 - 3 and 5- 13 are rejected under 35 U.S.C. 103 as being obvious over FILLIN "Insert the prior art reference." \d "[ 2 ]" Xia et al., (US 2008/0213895; published 11/4/2008) and Schmidt-Wolf et al. (from IDS, NPL cite No. 6; Journal of Experimental Medicine, 1991 , 174(1) ) . Xia et al. teaches D-CIK cells, provided as a vaccine for the treatment of parasite infections resulting from Plasmodium falciparum ; and thus anticipates instant claims 1-3 and 5- 6 , as described above. However, Xia does not teach wherein the CIK cells are treated with IFN-γ, or following the same protocol as those of instant claims 7-13. Schmidt-Wolf teaches the evaluation of CIK cells with potent antitumor cell activity (title). Schmidt-Wolf teaches a protocol using cytotoxic effector cells was developed by growing peripheral blood mononuclear cells in the presence of IFN-γ, anti-CD3 monoclonal antibody and IL-2; and that the timing of IFN-γ treatment was critical and optimal if IFN-γ was added before IL-2 treatment. Schmidt-Wolf teaches IFN-γ addition resulted in an increase in cytotoxic activity only if added 24 hours before the addition of IL-2 (pg. 141, col. 2, para. 2). Specifically, Schmidt-Wolf teaches the protocol for generating CIK cells comprises adding 1,000 U/mL IFN-γ to isolated cell cultures on day 0; after 24 hours of incubation, 50 ng/mL CD3 mAb , 300 u/mL IL-2 , and 100 U/mL IL-1 were added, and fresh IL-2 and fresh medium were added every 3 days (pg. 140, col. 1, para. 5). Thus, the protocol of Schmidt-Wolf (1991) teaches the same agents, concentrations and order of application to produce CIK cells as the instant claims. It would have been obvious to modify the protocol for generating D-CIK cells of Xia, to incorporate the IFN-γ agent and following the order of application of agents of Schmidt-Wolf. One would have been motivated to do so as a simple substitution of CIK-generating protocols known in the art, with the potential advantage of obtaining CIK cells that have greater cytotoxicity, as taught by Schmidt-Wolf. There would have been a reasonable expectation for success given that the CIK cells of Xia , for use in generating D-CIK cells, are generated from the same PBMCs, following a similar protocol for generating CIK cells, and which utilizes IL-2, IL-1 and anti-CD3 mAb , whereby the only alteration is the inclusion of IFN-γ for 24 hours prior to incubation with the other agents, which was taught to increase the resulting cytotoxicity of the CIK cells by Schmidt-Wolf. Thus, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made. MPEP 2143(I) provides examples of rationales that support a conclusion of obviousness, including (B)-simple substitution of one known element for another to obtain predictable results, and (C)- use of known techniques to improve similar methods in the same way, and (D) applying a known technique to a known method ready for improvement to yield predictable results. Here, the modification of the protocol for generating CIK cells of Xia, to further include a pre-incubation with IFN-γ for 24 hours, and whereby the cells are maintained in fresh IL-2 every 3 days thereafter, is a simple substitution of the protocol for generating CIK cells of Schmidt-Wolf; whereby the added steps/agents enhance the cytotoxic activity of the resulting CIK cells. As both of the protoco ls of Xia and Schmidt-Wolf w ere in the public domain at the time of the invention, the skilled artisan would have had a reasonable expectation for success in substituting one CIK-generating protocol for the other. Regarding claims 7-9 and 12 ; the protocol for generating CIK cells of Schmidt-Wolf, in the combination methods of Xia and Schmidt-Wolf, recites adding IFN-γ for 24 hours before adding IL-1β, IL-2 and anti-CD3 antibody the following day , and further includes adding fresh IL-2 every 3 days thereafter . Thus the combination methods of Xia and Schmidt-Wolf make obvious wherein the CIK cells were generated according to the protocol of instant claims 7-9 . As Xia teaches the cells are eukaryotic PBMCs, combination methods of Xia and Schmidt-Wolf make obvious instant claim 12 . Regarding claims 10-11 and 13 ; the protocol of Schmidt-Wolf recites 1,000 U/mL IFN-γ to isolated cell cultures on day 0; after 24 hours of incubation, 50 ng/mL CD3 mAb , 100 U/mL IL- 1, and 300 u/mL IL-2 were added, and fresh IL-2 and fresh medium were added every 3 days (pg. 140, col. 1, para. 5). Thus, the combination method of Xia and Schmidt-Wolf make obvious the protocol of instant claim 10 . Regarding claim 11 , Schmidt-Wolf teaches that cells were cultured in IL-2, IFN-γ, IL-1 and anti-CD3 antibody for 21 days, resulting in a proliferation of millions of cells across the 21 days (see pg. 141, Figure 1) ; and an increase in the tumor cell killing in a cytotoxic assay, whereby cell number peaked at ~21-28 days, and maximal activity was noticed between days 10 and 28 (pg. 141, col. 2, para. 2). Thus, Schmidt-Wolf makes obvious whereby the cells are matured for 2-3 weeks, and the combination method of Xia and Schmidt-Wolf makes obvious instant claim 11 . Claim 13 is made obvious over Xia and Schmidt-Wolf as routine optimization of the protocol. MPEP 2144.05(II)(A) discusses routine optimization, “differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such a concentration is critical; where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” Claim 10 recites wherein the concentration of IL-2 is 300-900 IU/mL; claim 11 recites wherein the concentration of IL-2 is 600 IU/ mL. Schmidt-Wolf teaches the concentration of IL-2 is 300 IU/ mL. Xia also teaches applying IL-2 to generate CIK cells, including adding fresh IL-2 to the cell culture every 3 days thereafter, similarly to Schmidt-Wolf. Xia teaches that 1000 U/mL of IL-2 is applied. Thus, both Schmidt-Wolf and Xia teach adding IL-2 in a protocol to generate CIK cells, whereby Schmidt-Wolf teaches it is 300 IU/mL and Xia teaches it is 1000 U/ mL. Therefore, a skilled artisan would have a range of 300-1000 IU/mL of IL-2 that may be applied , based on the teachings of the prior art. To determine a concentration of 600 IU/mL of IL-2 would thus be a matter of routine experimentation in order to find the optimal concentration , within the range taught by the art, of IL-2 to apply to generate CIK cells. Thus, the combination methods of Xia and Schmidt-Wolf make obvious instant claim 13 . Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JAMES R. MELCHIOR whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-4761 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8:00-5:00 CST . 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, FILLIN "SPE Name?" \* MERGEFORMAT Samira Jean-Louis can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 270-3503 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JAMES RYLAND MELCHIOR/ Examiner, Art Unit 1644 /NELSON B MOSELEY II/ Primary Examiner, Art Unit 1642