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 .
Detailed Action
Pursuant to a preliminary amendment filed on November 4, 2024, claims 1 - 20 are currently pending in the instant application. Claims 1, 19 and 20 are independent claims.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on November 4, 2024, and May 29, 2026 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed November 4, 2024, is a CONTINUATION of PCT/US2023/021259, filed May 5, 2023, which claims the benefit of Provisional application 63/364,409, filed May 9, 2022.
Therefore, the earliest priority date is May 9, 2022.
Claim Rejection - 35 USC § 112(b)
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 1- 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.
Claims 1, 3, 19, and 20 are indefinite because of its recitation in line 5 of the term “and/or.” It is unclear what the metes and bounds of these claims are, and what exactly is being treated. Thus, the metes and bounds of the claim cannot be determined.
Claims 2, and 4 – 18 are indefinite insofar as they ultimately depend on claim 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 20 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more. The claim recites a mitlet comprising platelet-derived extracellular vesicles (PEVs) that include mitochondria for use in treatment of cardiogenic shock and/or sepsis. This judicial exception is not integrated into a practical application because the product (a therapeutic product that consists of mitlets) does not differ from its naturally occurring counterpart. Even though the PEVs are collected by obtaining the blood, adding an anti-coagulant and a buffer, separating the mix, collecting the PRP, stimulating the collected PRP, expelling the extracellular vesicles from platelets, and collecting the extracellular vesicles as the PEVs (as recited claim 20), none of these limitations differentiate the claimed mitlet from their naturally occurring counterpart. More specifically, the mitlets comprising PEVs that include mitochondria are not distinguishable from their naturally-occurring counterparts, which are that mitlets are small extracellular vesicles, produced from platelets, that contain fragments of mitochondria. Biotech Bay teaches that “mitlets” are blood components, specifically small vesicles that contain mitochondria, ejected by platelets which potentially could be transfused into patients (pg. 1, second paragraph) (Biotech Bay, Mitrix Bio Publishes Details of “Mitlets” - Newly Discovered Blood Transfusion Components Containing Donor Mitochondria, October 26, 2021). Further, as shown supra, Marcoux teaches that PVs that convey mitochondrial components are isolated from whole blood of mice (pg. 2609, left column, second paragraph).
The claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim elements required by the claims is the process by which the PEVs are collect, so they are not additional elements claimed that need to be assessed to determine if they amount to significantly more.
Claim Rejection - 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 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.
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 - 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ostermeier et al. (hereinafter referred to as “Ostermeier”) (Ostermeier B. et al. Int J Mol Sci. 2022 Feb 19;23(4):2321. doi: 10.3390/ijms23042321.), and further in view of Marcoux G et al. (hereinafter referred to as “Marcoux”) (Marcoux G. et al. Blood. 2021 Dec 23;138(25):2607-2620. doi: 10.1182/blood.2020009957. ),, as evidenced by as evidenced by Roffi et al. (Roffi A. et al. Biomed Res Int. 2014;2014:692913. doi: 10.1155/2014/692913. Epub 2014 Jul 17.), and Barrett et al. (US 20170296700 A1, published October 19, 2017).
Regarding claims 1 (in part), 2 - 9, and 18, Ostermeier teaches that platelet extracellular vesicle therapy (pEV) therapy is used for treating viral diseases (Figure 5). Ostermeier teaches that platelets are derived from PRP, and the pEVs would be isolated and administered to treat patients with severe viral inventions (Figure 5) (interpreted as the PEVs have been collected at a different site than a site where a treatment is carried out, instant claim 2, and an effective amount, instant claim 18). Ostermeier teaches pEVs are typically isolated from plasma using differential centrifugation, wherein many current methods use platelet-rich plasma (PRP) for the isolation of EVs generally (PRP-EVs) (pg. 12, fourth paragraph). Ostermeier teaches PRP therapy has also been explored for the treatment of viral diseases, including severe COVID-19 (pg. 12, fourth paragraph) (referring to instant claims 3 – 7). Ostermeier teaches PRP-EVs and PRP-Exos have been used in the treatment of several diseases and conditions, including cancer, pneumonia, atherosclerosis, rheumatoid arthritis, chronic wounds, muscle injury, and hemorrhagic shock (Table 1) (interpreted as administering the mitlets into the subject, instant claim 9). Ostermeier teaches PMVs are a subject of platelet EVs that are released from platelets through blebbing, and retained mitochondrial components (pg. 7, second paragraph). Ostermeier teaches that sCD40L levels are found to be associated with severe COVID-19 manifestations, such as myocardial dysfunctions (interpreted as treating cardiogenic shock, or symptoms thereof, instant claim 1 (in part) and that COVID-19 preceds cardiogenic shock, instant claim 8)).
Ostermeier does not specifically exemplify the process of obtaining the PEVS (referring to instant claims 1, 10, 11, 13 – 16, 19, and 20).
Regarding claims 1, 10, 11, 13 – 16, 19, and 20, Marcoux teaches platelet-derived extracellular vesicles (PEVs) convey mitochondrial components that are associated with inflammation and adverse transfusion reactions (ATRs) (pg. 2609, left column, second paragraph) (interpreted as a mitlet comprising a PEV that includes mitochondria, instant claims 1, 19, and 20). Marcoux teaches that platelets were isolated from mice, wherein the whole blood was centrifuged to remove the red blood cells, and the platelet-containing pellet was resuspended in Tyrode’s buffer, and thereafter, activated with thrombin and calcium (pg. 2609, right column, first paragraph) (interpreted as stimulated with complexes in presence of Ca2+, instant claim 10 and 13, and claim 15). Marcoux teaches that PEVs were obtained by 2 rounds of centrifugation (pg. 2609, right column, first paragraph) (referring to claim 16). Marcoux teaches that the platelets were isolated in 200 µL ACD (pg. 2609, left column, last paragraph) (referring to instant claim 14). Marcoux teaches that heat-aggregated IgG (HA-IgG) also triggered release of proteasome-containing PEVs (supplemental Figure 2C) (interpreted as the immune complexes comprise heat-aggregated IgG, instant claims 11 and 13). Marcoux teaches that platelet EVs (PEVs) are thought to perform diverse functions (Abstract).
Therefore, in view of the benefits the role of platelet EVs (PEVs) in having a role in many diverse functions as taught by Ostermeier, it would have been prima facia obvious for one of ordinary skill in the art to use the PEVs are used to treat viral diseases, as taught by Ostermeier, and follow the protocol for obtaining the PEVs from whole blood of mice, as taught by Marcoux, with a reasonable expectation of success of isolating the PEVs that convey mitochondrial components, and use them for treatment of viral diseases. It would have been prima facia obvious to combine the cited sources because Ostermeier teaches that the PEVs are used to treat viral diseases, and that pEVs are isolated using differential centrifugation, specifically using the platelet-rich plasma (PRP) for the isolation of EVs generally (PRP-EVs), and Marcoux teaches the protocol for obtaining PEVs, including separating the supernatant and the platelet-containing pellet, and that the PEVs are used for many diverse functions.
Regarding claim 12, Marcoux and Ostermeier do not specifically teach that the PRP is stimulated by freeze-thaw cycles. However, one of ordinary skill in the art would know that the PRP is stimulated by freeze-thaw cycles, as evidenced by Roffi et al. Roffi et al. teaches PRP was freeze-thawed (Abstract).
Regarding claim 17, Marcoux and Ostermeier do not specifically exemplify that the blood has been stored four or more days. However, one of ordinary skill in the art would know the best way to store the collected samples, such as evidenced by Roffi et al. Roffi et al. teaches that the tests were done with fresh or frozen PRP (Abstract).
Regarding claim 19, Marcoux and Ostermeier do not specifically teach that the source cells are grown in a bioreactor. However, one of ordinary skill in the art would know how to grow source cells in a bioreactor, such as evidenced by Barrett et al.
The examiner notes that the platelet-derived extracellular vesicles (PEVs) in claims 1 and 19 are recited as a product by process claim. Since the U.S. Patent and Trademark Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make comparisons therewith, a lesser burden of proof is required to make out a case of prima facie anticipation/obviousness for product-by-process claims because of their peculiar nature than when a product is claimed in the conventional manner. MPEP 2113. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.
Conclusion
Claims 1-20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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