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 .
Election/Restrictions
Applicant’s election of Group I (claims 1-27) in the reply filed on 7/6/2026 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)).
Claim 35 is newly added, claims 28-35 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-27 have been considered on the merits.
Drawings
The drawings are objected to because Fig. 2A discloses two tables with Japanese letters; and Fig. 3B contains Japanese letters. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description Rejection
Claims 1-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a method of generating “mitochondria replaced lymphoid cells” in which at least 20% of endogenous mitochondrial DNA (mtDNA) has been replaced with exogenous mtDNA by incubating the lymphoid cells that have not undergone a procedure to reduce or deplete endogenous mitochondria with isolated exogenous mitochondria and an effective amount of an mTOR inhibitor.
The claims require the lymphoid cells that have not undergone any reduction or depletion of the endogenous mitochondria or mtDNA. It is construed that in order to obtain the claimed result of “mitochondria replaced” lymphoid cells, the claimed method should somehow reduce or deplete the endogenous mitochondria or mtDNA as the prior reduction or depletion is excluded. It is understood that the exogenous mitochondria would enter the cells when co-incubated, and this non-invasive transfer would populate the exogenous mitochondria in the target cells (i.e. lymphoid cells). However, there is no disclosure in the instant specification if the non-invasive transfer of the exogenous mitochondria would reduce or deplete the endogenous mitochondria of the lymphoid cells. The instant specification merely state that the claimed incubation would necessarily “replace” the endogenous mitochondria with the exogenous mitochondria. Considering the term “replace” requires reduction or depletion of endogenous mitochondria, and there is no evidence that the number or amount of endogenous mitochondria or mtDNA by merely incubating the lymphoid cells with the exogenous mitochondria, it is considered that the inventors did not have possession of the claimed invention.
Gojo et al. (US2020/0054682A1; IDS ref.) teach that the mitochondria replaced cells (MirC) requires a step of reducing endogenous mitochondria or mtDNA (para. 242). Furthermore, Gojo et al. teach that “adding on” the mitochondria without partially reducing the endogenous mtDNA (para. 366), indicating that the instant claims are directed to “adding on” of the exogenous mitochondria to the recipient cells rather than “replacing” the endogenous mitochondria.
M.P.E.P. §2163 states “To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.”
M.P.E.P. § 2163 also recites, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention… one must define a compound by ‘whatever characteristics sufficiently distinguish it’. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.” and further, “The description needed to satisfy the requirements of 35 U.S.C. 112 "varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.< Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art. In most technologies which are mature, and wherein the knowledge and level of skill in the art is high, a written description question should not be raised for claims >present in the application when originally filed,< even if the specification discloses only a method of making the invention and the function of the invention. See, e.g., In re Hayes Microcomputer Products, Inc. Patent Litigation, 982 F.2d 1527, 1534-35, 25 USPQ2d 1241, 1246 (Fed. Cir. 1992) ("One skilled in the art would know how to program a microprocessor to perform the necessary steps described in the specification. Thus, an inventor is not required to describe every detail of his invention. An applicant's disclosure obligation varies according to the art to which the invention pertains. Disclosing a microprocessor capable of performing certain functions is sufficient to satisfy the requirement of section 112, first paragraph, when one skilled in the relevant art would understand what is intended and know how to carry it out."). In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.”
Enablement Rejection
Claims 1-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 USPQd 1400, 1404 (Fed. Cir. 1988) (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
The instant claims are directed to a method of generating “mitochondria replaced lymphoid cells” in which at least 20% of endogenous mitochondrial DNA (mtDNA) has been replaced with exogenous mtDNA by incubating the lymphoid cells that have not undergone a procedure to reduce or deplete endogenous mitochondria with isolated exogenous mitochondria and an effective amount of an mTOR inhibitor.
The scope of the instant claims is to obtain “mitochondria replaced lymphoid cells” by carrying out the steps of the claimed method. The method steps require to incubate lymphoid cells with isolated exogenous mitochondria in the presence of effective amount of an mTOR inhibitor. Yet the claimed method specifically exclude any manipulation of reducing or depleting endogenous mitochondria of the lymphoid cells.
The state of the prior art with regard to the mitochondrial transfer or mitochondria replacement is relatively high. Kitani et al. (2014, J. Cell. Mol. Med.; IDS ref.) teach a method of internalization of isolated functional mitochondria into cells with mitochondrial dysfunction. Gojo et al. (supra) teach a method of transferring exogenous mitochondria into the cells having been undergone a procedure to reduce or deplete the endogenous mitochondria. The phenomenon of non-invasive transfer of exogenous mitochondria being internalized appears to be mediated by macropinocytosis according to Kitani et al.
While the prior art recognizes mitochondrial transfer or replacement as naturally occurring phenomenon, however, there is no indication that the incubating and transferring exogenous mitochondria into the recipient cells would necessarily and sufficiently replace, i.e. reduce or deplete, the endogenous mitochondria. Rather, it is more likely that the exogenous mitochondria would be “added” to the endogenous mitochondria. Only when the recipient cells are reduced or depleted with the endogenous mitochondria and then exogenous mitochondria being transferred into the recipient cells, the exogenous mitochondria would functionally replace the reduced or depleted endogenous mitochondria. In other words, without reducing or depleting the endogenous mitochondria prior to the mitochondrial transfer, one cannot generate the claimed “mitochondria replaced cells”.
Rather Gojo et al. teach that there is no effect of modulating mTORC1 activity. Gojo et al. teach that notably, in both mock transfection and add-on type mitochondrial
transfer, there were no significant differences. In addition, the results showed that the effect of modulating mTORC1 activity only affected mitochondrial transfer of p(-) cells, and had no effect on "add on" or mock transfected cells (para. 383). Considering that the claimed method appears to be consistent with “add on” type of mitochondrial transfer because the endogenous mitochondria are not reduced or depleted, Gojo et al. provide evidence that the presence of mTOR inhibitor does not affect the transfer. Furthermore, Gojo et al. provide evidence that add-on type mitochondria transfer was unable to even increase the number of mtDNA copies in spite of the same cocultivation with isolated mitochondria under the same conditions (para. 387). Based on the teachings of Gojo et al., it is highly unpredictable if the lymphoid cells that have not undergone reduction or depletion of the endogenous mitochondria would be able to transfer exogenous mitochondria, and even if it does, there is no predictability that such transfer would replace the endogenous mitochondria.
The instant specification fails to provide whether or not the claimed method would reduce or deplete the endogenous mitochondria via the claimed method. There is no evidence that the claimed incubation of lymphoid cells that have not undergone a procedure to reduce or deplete the endogenous mitochondria with the isolated exogenous mitochondria with an mTOR inhibitor results in the exogenous mitochondria replacing the endogenous mitochondria. Rather, the specification merely states that the method would necessarily product the claimed mitochondria replaced cell without any evidence or data.
In the absence of clear evidence, example or guidance in addition to no known knowledge in the art with regard to the claimed outcome of generating mitochondria replaced lymphoid cells, it is highly unpredictable that the claimed method steps would necessarily produce the claimed “mitochondria replaced lymphoid cells” without undue experimentations.
M.P.E.P. § 2164.03 reads, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The ‘amount of guidance or direction’ refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004) (“In applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required.”).”
The level of one of ordinary skill in the art at the time of invention was advanced, being that of a person holding a Ph.D. or an M.D.; however, because of its unpredictability, as shown by the other factors discussed above, one of skill in the art at the time of invention by Applicant would not have been able to make and/or use the invention claimed, to its fully-claimed scope, without undue experimentation.
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 1-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: reducing or depleting endogenous mitochondria from the lymphoid cells.
The instant claims are directed to generate “mitochondria replaced lymphoid cells” by incubating lymphoid cells with isolated exogenous mitochondria and an mTOR inhibitor. The claims disclose that at least 20% of endogenous mitochondrial DNA (mtDNA) has been replaced with exogenous mtDNA. The term “replaced” implies that the lymphoid cells utilized in the claimed method are required to be reduced or depleted with endogenous mitochondria as the exogenous mitochondria would “replace” the endogenous mitochondria based on the definition given to the term “mitochondria replaced lymphoid cells” (para. 23).
The instant claims however require that the lymphoid cells have not undergone a procedure to reduce or deplete endogenous mitochondria. If the claimed method is considered to “replace” the endogenous mitochondria of the lymphoid cells by incubating and thus, transferring the exogenous mitochondria, the claimed method should somehow get rid of the endogenous mitochondria. However, the claims require not to manipulate the lymphoid cells to reduce or deplete endogenous mitochondria. Without reducing or depleting the endogenous mitochondria, the claims cannot be considered producing “mitochondria replaced” lymphoid cells, rather they are directed to the exogenous mitochondria added lymphoid cells. Clarification is required.
Claim 10 contains the trademark/trade name “TaqMan®”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a product used for polymorphism assay and, accordingly, the identification/description is indefinite.
Claim 12 discloses a wherein clause that the isolated exogenous mitochondria is about 20-80 mg protein per 1x106 cells. It is not clear if the amount in the wherein clause is a yield from a million cells or the amount is used in the incubation. In other words, the term “cells” is not clear if it refers to the lymphoid cells or the cells from which the exogenous mitochondria are isolated.
Claim 15 discloses “at least approximately” in line 2. It is not clear what is included or excluded for the sufficient period of time. The term “at least” which requires a number for the lower end, i.e. at the minimum requirement, and the term “approximately” does not provide clear boundary of the range. Thus, one cannot determine what the minimum number of the claimed range, and thus, it is indefinite by using “at least” and “approximately” together in defining the range in the claims. Applicant is advised to delete the term “at least” or “approximately”.
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.
Claim(s) 1-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gojo et al. (supra) in view of Kitani et al. (supra).
It is noted that the instant claims are interpreted as a method of incubating lymphoid cells that have not undergone a procedure to reduce or deplete endogenous mitochondria with isolated exogenous mitochondria with an effective amount of mTOR inhibitor.
Gojo et al. teach a method of generating a mitochondria replaced cell, comprising:
(a) contacting a recipient cell with an agent that reduces endogenous mtDNA copy number;
(b) incubating the recipient cell for a sufficient period of time for the agent to partially reduce the endogenous mtDNA copy number in the recipient cell; and
(c) co-incubating (1) the recipient cell from step (b) in which the endogenous mtDNA has been partially reduced, and (2) exogenous mitochondria or exogenous mtDNA from a healthy donor, for a sufficient period of time to non-invasively transfer the exogenous mitochondria or the exogenous mtDNA into the recipient cell, thereby generating a mitochondria replaced cell (p.52, Claim 1; para. 13).
Gojo et al. also teach the step of contacting the recipient cell with a second active agent prior to co-incubating the recipient cell with exogenous mitochondria and/or exogenous mtDNA, wherein the second active agent is optionally selected from the group consisting of large molecules, small molecules, or cell therapies, and the second active agent is optionally selected from the group consisting of rapamycin (p.53, claim 61; para. 35).
Gojo et al. teach that the recipient cells may be obtained directly from a mammal, preferably human, and include B cells, T cells, macrophages, etc. (para. 265), and thus, the teaching meets the lymphoid cells of claim 1, 24-25 and 27.
Regarding the lymphoid cells that have not undergone a procedure to reduce or deplete endogenous mitochondria, Gojo et al. teach the recipient cells used for control cells are without electroporation and the endogenous mitochondria are not reduced or depleted. The control cells are then co-incubated with exogenous mitochondria or added by centrifugation (i.e. “add-on”) (para. 232). This teaching is considered to meet the claimed method utilizing the lymphoid cells that are not undergone to reduce or deplete the endogenous mitochondria.
Gojo et al. teach the sufficient period of time for the incubating step, and they also teach identifying the "sufficient period of time" to non-invasively transfer exogenous mitochondria and/or exogenous mtDNA into the recipient cell is within the skill of those in the art (para. 260).
Regarding the results of the claimed method directed to at least 20% of endogenous mitochondrial DNA being replaced with exogenous mtDNA, Gojo et al. do not teach the limitation. However, the results of the claimed method do not require any other active step than incubating lymphoid cells with isolated exogenous mitochondria in the presence of mTOR inhibitor including rapamycin. As the method taught by Gojo et al. as discussed above discloses identical steps and materials, the results of the Gojo et al.’s method are expected the same as the claimed method.
Regarding claims 2-3, Gojo et al. teach rapamycin or a derivative thereof (para. 275).
Regarding claims 4-9, 11 and 21 directed to the concentration of mTOR inhibitor, the claimed range of the concentration is broad from about 100 nM to 1000 nM. Gojo et al. teach that rapamycin was added into the culture media at the concentration of 50 ng/ml for 24 hours (para. 380). The concentration can be converted to about 50 nM, and thus, this concentration is lower than the claimed concentrations. However, one skilled in the art would recognize that the concentration of mTOR inhibitor for the purpose of improving mitochondria transfer is a result-effective parameter as it is utilized for modulating cellular metabolism by nutrient starvation or nutrient deprivation (para. 274), and thus, the concentration of mTOR inhibitor including rapamycin can be modified by routine experimentations.
It is well settled that routine optimization is not patentable, even if it results in significant improvements over the prior art. In support of this position, attention is directed to the decision in In re Aller, Lacey, and Haft, 105 USPQ 233 (CCPA 1955): Normally, it is to be expected that a change in temperature, or in concentration, or in both, would be an unpatentable modification. Under some circumstances, however, changes such as these may impart patentability to a process if the particular ranges claimed produce a new and unexpected result which is different in kind and not merely in degree from the results of the prior art. In re Dreyfus, 22 C.C.P.A. (Patents) 830, 73 F.2d 931,24 USPQ 52; In re Waite et al., 35 C.C.P.A. (Patents) 1117, 168 F.2d 104, 77 USPQ 586. Such ranges are termed "critical" ranges, and the applicant has the burden of proving such criticality. In re Swenson et al., 30 C.C.P.A. (Patents) 809, 132 F.2d 1020, 56 USPQ 372; In re Scherl, 33 C.C.P.A. (Patents) 1193, 156 F.2d 72, 70 USPQ 204. However, even though applicant's modification results in great improvement and utility over the prior art, it may still not be patentable if the modification was within the capabilities of one skilled in the art. In re Sola, 22 C.C.P.A. (Patents) 1313, 77 F.2d 627, 25 USPQ 433; In re Normann et al., 32 C.C.P.A. (Patents) 1248, 150 F.2d 708, 66 USPQ 308; In re Irmscher, 32 C.C.P.A. (Patents) 1259, 150 F.2d 705, 66 USPQ 314. More particularly, 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. In re Swain et al., 33 C.C.P.A. (Patents) 1250, 156 F.2d 239, 70 USPQ 412; Minnesota Mining and Mfg. Co. v. Coe, 69 App. D.C. 217, 99 F.2d 986, 38 USPQ 213; Allen et al. v. Coe, 77 App. D. C. 324, 135 F.2d 11,57 USPQ 136. (Emphasis added). With regards to determining experimental parameters, such as time in culture, the court has held that "[d]iscovery of optimum value of result effective variable in known process is ordinarily within skill of art (In re Boesch and Slaney, 205 USPQ 215 (CCPA 1980)).
The adjustment of particular conventional working conditions (e.g., concentration) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan having the cited reference before him/her.
Regarding claim 10, the wherein clause is directed to the results and the results are measured by TaqMan SNP assay. This limitation does not provide any active step to be carried out for the claimed method of generating mitochondria replaced lymphoid cells, and it is considered as optional (see MPEP 2111.04). Thus, the limitation does not provide any weight in determining the claimed method. Nevertheless, Gojo et al. teach the use of TaqMan SNP assay for evaluating the extent of the exchange of mtDNA (para. 414).
Regarding claims 13-14 and 21 directed to centrifuging the lymphoid cells before incubating, and the centrifugal force being 1,500 rcf (i.e. xg), Gojo et al. teach the method of their invention can be performed in combination with centrifugation (para. 366), and the centrifugation refers to spinoculation at 1500xg (para.363). While Gojo et al. do not particularly disclose the order, however, it would have been obvious that incubation and spinoculation can be in any order, and thus, centrifuging prior to incubation is an obvious option to a person skilled in the art.
Regarding claims 15-20 and 21-23 directed to the sufficient period of time being at least approximately 24 hours up to 7 days or more, Gojo et al. teach that the sufficient period of time to non-invasively transfer exogenous mitochondria and/or exogenous mtDNA into a recipient cell is about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, about 1-2 weeks, about 2-3 weeks or about 3-4 weeks (para. 260).
Regarding claim 26, Gojo et al. teach that the recipient cell is an exhausted T cell (para. 269).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gojo et al. as applied to claim 1 above, and further in view of Liao et al. (2020, Methods Cell Biol.).
Regarding claim 12 directed to the amount of isolated exogenous mitochondria being about 20-80 mg protein per million cells, Gojo et al. do not teach the limitation. The wherein clause of claim 12 is interpreted that the yield of the mitochondria from a million cells, rather than the amount actually used in the incubation.
Liao et al. teach that the crude mitochondria isolated from cultured cells can vary from 7 to 50 mg of mitochondrial protein per 106 cells (p.14, Analysis and statistics).
It would have been obvious to a person skilled in the art to comprise the claimed amount of mitochondrial protein per a million cells from the method of Gojo et al. as it is known in the art that human cultured cells (e.g. HeLa cells) can produce 7-50 mg of mitochondrial protein per 106 cells which is overlapping with the claimed range. Thus, one skilled in the art would expect that the amount of the isolated mitochondria of Gojo et al. would fall in the range taught by Liao et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/TAEYOON KIM/ Primary Examiner, Art Unit 1631
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