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
This application is a 371 of PCT/CN2021/081711, filed 3/19/2021. This application claims benefit to foreign application CHINA 202110281102.5, filed 3/16/2021. Claims 7-8 and 11-20 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statements submitted on 11/10/2023, 12/13/2023 (2), 12/17/2024 and 6/11/2025 have been considered by the examiner. Foreign patent document cite 1 of the 5-page IDS from 12/13/2023 is lined through because the document has not been received. U.S. Patent cites 1-2 of the 12/17/2024 IDS are lined through because they are already of record (U.S. Patent cites 1-2, 5-page IDS, 12/13/2023). NPL cite 2 of the 6/11/2025 IDS is lined through because the document is missing almost all of the cited poster (reference states pp. e175-176, but received document is e176-e177).
Claim Objections
Claim 12 is objected to because of the following informalities:
Claim 12 recites “amount of Plasmodium to subject” in lines 1-2 which should be “amount of Plasmodium to subject” because taxonomic names are italicized. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11, 13, 15-17 and 20 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 11 recites the broad recitation “wherein a dosage form of the preparation comprises any one of pharmaceutically acceptable dosage forms”, and the claim also recites “preferably, the preparation further comprises any one or a combination of at least two of pharmaceutically acceptable pharmaceutical adjuvants” which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Likewise, claim 13 recites the broad recitation “wherein the Plasmodium comprises any one or a combination of at least two of Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale or Plasmodium knowlesi”, and the claim also recites “and preferably is Plasmodium vivax” which is the narrower statement of the range/limitation.
Claim 15 recites the broad recitation “wherein the radiotherapy comprises an alpha ray, a beta ray, a gamma ray, an X ray, a heavy ion ray, an electron beam or a proton beam”, and the claim also recites “preferably, the radiotherapy comprises a single radiotherapy, a multiple radiotherapy or a fractionation radiotherapy” and “preferably, the radiotherapy comprises a systemic radiotherapy or a local radiotherapy” which are the narrower statements of the range/limitation.
Claim 17 recites the broad recitation “wherein the Plasmodium is a Plasmodium carried on a pharmaceutical carrier”, and the claim also recites “preferably, the pharmaceutical earner comprises a liposome, a micelle, a dendrimer, a microsphere or a microcapsule” which is the narrower statement of the range/limitation.
Claim 20 recites the broad recitation “wherein an administration manner of the Plasmodium comprises intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration or percutaneous administration”, and the claim also recites “preferably is intravenous injection” which is the narrower statement of the range/limitation.
The claims are considered indefinite because there is a question or doubt as to whether the features introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 16, the claim recites “wherein the tumor comprises a lung cancer, a gastric cancer, a colon cancer, a liver cancer, a breast cancer, a prostate cancer, an ovarian cancer, a pancreatic cancer, and a brain tumor” which is indefinite because the list appears to be a list of alternatives but the alternatives are separated by “and”; hence, it is indefinite whether a list of alternatives or a Markush group is intended to be recited. If the list were a Markush group, the claim should state “wherein the tumor is from the group consisting of a lung cancer, a gastric cancer, a colon cancer, a liver cancer, a breast cancer, a prostate cancer, an ovarian cancer, a pancreatic cancer, and a brain tumor” or equivalent language. If the list is to be a list of alternatives, the claim should state “wherein the tumor comprises a lung cancer, a gastric cancer, a colon cancer, a liver cancer, a breast cancer, a prostate cancer, an ovarian cancer, a pancreatic cancer or a brain tumor” or equivalent language.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 7-8, 11-14, 16-17 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al., CN109999190 (Foreign Patent Document cite 3, 5 pg. IDS, 12/13/2023; WIPO English translation of CN109999190 (cite U, attached PTO-892; herein “Liu”) is used for the citations in the rejection) in light of Molina-Cruz et al., 2012 (cite V, attached PTO-892; herein “Molina-Cruz”).
NOTE: Claims 7-8 and 11 are composition claims. Intended use recitations in composition claims, such as “for use in combination with radiotherapy” in claim 7 and “wherein the preparation and the radiotherapy are administered concurrently” in claim 8, are met if the composition can be used for the intended use regardless of whether or not the prior art reference discloses the method.
Liu teaches anti-tumor Plasmodium preparations (Abst.) anticipating claims 7-8. Liu teaches that the anti-tumor Plasmodium preparation can be in different dosage forms such as a tablet, suspension, an injection, etc. (p. 3 of the pdf, “Summary of the Invention”, ¶6) anticipating claim 11.
Liu teaches that the anti-tumor Plasmodium preparation can be used for treating cancer, preferably colon or liver cancer, by combination therapy with radiation therapy (p. 3 of the pdf, “Summary of the Invention”, ¶4-10) anticipating claims 12 and 16.
Liu teaches that the anti-tumor Plasmodium preparation is prepared with PfNF54 strain (p. 4 of the pdf; “Example 1”), which is a commonly used laboratory strain of Plasmodium falciparum (see evidentiary reference Molina-Cruz, whole document, for confirmation that the PfNF54 strain is a Plasmodium falciparum strain) anticipating claim 13.
Liu demonstrates that the anti-tumor Plasmodium falciparum preparation is effective for treating colon cancer (pp. 5-6 of the pdf, “Example 3”) and liver cancer (p. 6 of the pdf, “Example 4”) wherein 100 µl of the anti-tumor Plasmodium falciparum preparation is injected intraperitoneally wherein the administered anti-tumor Plasmodium falciparum preparation comprises > 100 Plasmodia or > 5 Plasmodium sporozoites (p. 4 of the pdf, “Example 1, Preparation of Inactivating Plasmodium Suspension and Erythrocyte Suspension”) anticipating claims 14 and 20.
Liu teaches that the anti-tumor Plasmodium can be loaded on a pharmaceutical carrier wherein the carrier can comprise a liposome, a micelle, a dendrimer, a microsphere, or a microcapsule (p. 3 of the pdf, “SUMMARY OF THE INVENTION”, ¶8-9) anticipating claim 17.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 7-8 and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Liu in view of Kalogeridi et al., 2015 (cite W, attached PTO-892; herein “Kalogeridi”).
The discussion of Liu regarding claims 7-8, 11-14, 16-17 and 20 in the rejection set forth above is incorporated herein.
Liu teaches administering the anti-tumor Plasmodium preparation in combination therapy with radiation therapy to treat cancer (p. 3 of the pdf, “Summary of the Invention”, ¶4-10) but is silent on whether the radiation therapy comprises an alpha ray, a beta ray, a gamma ray, an X ray, a heavy ion ray, an electron beam or a proton beam; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the radiation therapy to comprise a beta ray, i.e., beta emissions, in view of the disclosure of Kalogeridi.
Kalogeridi teaches that radiotherapy is effective for hepatocellular carcinoma (Abst.), i.e., liver cancer, wherein the radiotherapy can comprise the subject receiving beta emissions (pp. 102-103, “Options of Radiotherapy”, “Internal radiotherapy”).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Liu in view of Kalogeridi wherein the radiotherapy comprises a beta ray; therefore, claim 15 is prima facie obvious.
Regarding claims 18-19, the radiotherapy and the Plasmodium can either be administered concurrently or non-concurrently, i.e., sequentially; hence, a person of ordinary skill in the art at the time of filing would have found it obvious to either administer the radiotherapy and the Plasmodium concurrently or sequentially; therefore, claims 18-19 are prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 7-8, 11-13 and 16-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14, 16 and 22-23 of copending Application No. 17/629673 (“’673” herein) in view of Liu.
Claim 14 of ‘673 recites a method for treating non-small cell lung cancer, comprising administering an effective amount of a Plasmodium and an effective amount of a chemotherapeutic agent to a subject in need thereof, wherein the Plasmodium is selected from Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium chabaudi (Pc), Plasmodium yoelii (Py), Plasmodium berghei and Plasmodium vinckei, and wherein the chemotherapeutic agent is selected from gemcitabine, cyclophosphamide, pemetrexed, cis-platinum and nelfinavir, and wherein the administration is by intraperitoneal injection or intravenous injection.
‘673 does not specifically recite administering the Plasmodium preparation in combination with radiation therapy; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the administration to further comprise radiation therapy in view of the disclosure of Liu.
Liu teaches that an anti-tumor Plasmodium preparation can be used for treating cancer by combination therapy with radiation therapy (p. 3 of the pdf, “Summary of the Invention”, ¶4-10); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to combine radiation therapy with the Plasmodium administration taught by ‘673; therefore, instant claims 7-8, 12-13, 16 and 20 are prima facie obvious.
Claim 16 of ‘673 recites the method according to claim 14, wherein the Plasmodium and the chemotherapeutic agent are in a combined pharmaceutical composition, wherein the combined pharmaceutical composition is in a dosage form that comprises any pharmaceutically acceptable dosage form; therefore, instant claim 11 is prima facie obvious.
Claim 22 of ‘673 recites the method according to claim 16, wherein the combined pharmaceutical composition is loaded on a pharmaceutical carrier; therefore, instant claim 17 is prima facie obvious.
Regarding instant claims 18-19, the radiotherapy and the Plasmodium can either be administered concurrently or non-concurrently, i.e., sequentially; hence, a person of ordinary skill in the art at the time of filing would have found it obvious to either administer the radiotherapy and the Plasmodium concurrently or sequentially; therefore, claims 18-19 are prima facie obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 7-8, 11-13 and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 9 and 10 of copending Application No. 17/910763 (herein “’763”) in view of Liu.
Claim 10 of ‘763 recites a method for treating brain tumors, comprising: (a) administering to patients a therapeutically effective amount of the drug according to claim 1; and (b) maintaining Plasmodium infection to a chronic or subacute phase; claim 1 of ‘‘763 recites a drug for preventing and/or treating brain tumors, wherein the drug comprises at least one Plasmodium strain; wherein the brain tumors are primary brain tumors or metastatic brain tumors; wherein the Plasmodium strain is cryopreserved and resuscitated Plasmodium strain; wherein the cryopreserved and resuscitated comprises the following steps: (1) cryopreservation of Plasmodium; (1.1) centrifuging whole blood containing Plasmodium at 300 x g for 5 minutes, and transferring plasma to another 50 mL centrifuge tube; (1.2) removing leukocyte layer, and adding 2 volumes of 1640 culture medium, mixing well and centrifuging at 300 x g for 5 minutes; (1.3) dropping an equal volume of 28% glycerol cryopreservation solution slowly into the 50 mL centrifuge tube, shaking and mixing well while adding, and incubating at room temperature for 5 minutes; (1.4) packing a REC-glycerol cryopreservation solution mixture separately in cryopreservation tubes, 1.0 mL per tube; (1.5) putting the cryopreservation tubes into a cryopreservation box and directly storing the cryopreservation box into liquid nitrogen; (1.6) performing quality control by adding a proper amount of the REC-glycerol cryopreservation solution mixture before cryopreservation to a proper amount of RPMI 1640 culture medium, culturing in an incubator with CO2 at 37°C for 72 hours, and observing the color of the culture medium to confirm absence of turbidity; (2) resuscitation of Plasmodium; (2.1) preparing a 37°C water bath cauldron, 50 mL centrifuge tubes, 3.5% NaCl solution, sodium chloride injection, a centrifuge, printed labels, and forms; (2.2) checking labels of cryopreservation tubes; (2.3) taking a cryopreserved Plasmodium blood and bath in water at 37°C for 1 to 3 minutes, mixing well quickly and thawing; (2.4) transferring the cryopreserved Plasmodium blood to a 15 mL centrifuge tube, adding an equal volume of 3.5% NaCl solution slowly along the tube wall, pipetting gently and mixing well, standing at room temperature for 5 minutes, and discarding a supernatant; (2.5) adding 5 volumes of 0.9% NaCl solution along the tube wall, pipetting gently and mixing well, centrifuging at 300 x g for 5 minutes, and discarding a supernatant; (2.6) adding normal saline to achieve 50% hematocrit, mixing well, counting and recording red blood cells density, and storing temporarily at 4°C for clinical inoculation; (2.7) performing quality control by smearing remaining blood samples, preparing blood smears, and observing parasitemia and Plasmodium status via microscopy before injection, and recording; and claim 4 of ‘763 recites the drug for preventing and/or treating brain tumors of claim 1, wherein the Plasmodium strains are selected from the group consisting of Plasmodium vivax and Plasmodium falciparum.
‘763 does not specifically recite administering the Plasmodium preparation in combination with radiation therapy; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the administration to further comprise radiation therapy in view of the disclosure of Liu.
Liu teaches that an anti-tumor Plasmodium preparation can be used for treating cancer by combination therapy with radiation therapy (p. 3 of the pdf, “Summary of the Invention”, ¶4-10); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to combine radiation therapy with the Plasmodium administration taught by ‘763; therefore, instant claims 7-8, 12-13 and 16 are prima facie obvious.
Claim 6 of ‘763 recites the drug for preventing and/or treating brain tumors of claim 1, wherein a dosage form of the drug is any pharmaceutically acceptable dosage form.; therefore, instant claim 11 is prima facie obvious.
Claim 9 of ‘763 recites the drug for preventing and/or treating brain tumors of claim 1, wherein the drug is a drug carried on a pharmaceutical carrier; preferably, wherein the pharmaceutical carrier comprises a liposome, a micelle, a dendrimer, a microsphere or a microcapsule; therefore, instant claim 17 is prima facie obvious.
Regarding instant claims 18-19, the radiotherapy and the Plasmodium can either be administered concurrently or non-concurrently, i.e., sequentially; hence, a person of ordinary skill in the art at the time of filing would have found it obvious to either administer the radiotherapy and the Plasmodium concurrently or sequentially; therefore, claims 18-19 are prima facie obvious.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651