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
Status of Application/Amendment/Claims
Applicant's response filed 11/12/2025 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 08/11/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 11/12/2025, claims 1-12 and 25-27 are pending in the application.
The 103 rejection is withdrawn in view of the new grounds of rejection.
Claim Objections
Claim 26 is objected to because of the following informalities: The claim recites an acronym “wherein administering the inhibitor results improves heteroplasmy in the cell” and would be clearer if it recites “wherein administering the inhibitor results in improved heteroplasmy in the cell. Appropriate correction is suggested.
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 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.
Claim(s) 1-4, 26 and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gibellini, Lara, et al. ("LonP1 differently modulates mitochondrial function and bioenergetics of primary versus metastatic colon cancer cells." Frontiers in oncology 8 (2018): 254).
Claim interpretation:
Claim 1 recites “ A method for depleting deleterious mitochondrial genomes (mtDNAs) in a cell, the method comprising administering an effective amount of an inhibitor of LONP1. The claim recites one method step of administering an effective amount of an inhibitor of LONP1 and thus any method step of administering an inhibitor in a cell targeted to LONP1 that is taught in the prior art would have any resulting step as further claimed. Moreover, a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951).
Gibellini et al. teach a method of administer a siRNA targeted against LONP1 mRNA in cancer cell lines (see page 2). The step of administration would result in a compensatory increase in wild type mtDNA of claim 2, improves heteroplasmy in the cell of claim 25 and reduces the ratio of mutated of claim and wild type mtDNA in the cell of claim 27.
Thus Gibellini et al. anticipates the claims.
Claim(s) 1-3, 6-9, 26 and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bartolomeo, Regina. "Effects of Lon protease silencing or inhibition on mitochondria of cancer cells."
Bartolomeo teach a method of decreasing Lon (also known as LONP1) comprising administering triterpenoid 2-cyano-3,12 dioxooleana-1,9,-dien-28-oic acid CDDO and its methylated form CDDO-Me into a colon cancer cell and to inhibit Lon (see page 75). The step of administration would result in a compensatory increase in wild type mtDNA of claim 2, improves heteroplasmy in the cell of claim 25 and reduces the ratio of mutated of claim and wild type mtDNA in the cell of claim 27.
Thus Bartolomeo anticipates the claims.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 1-12 and 25-27 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification,
while being enabling for RNAi against LONGp1 in C. elegans decreased mutated mtDNA and an shRNA targeted to ATFs increased heteroplasmy,
does not reasonably provide enablement for methods of depleting deleterious mitochondrial genomes using any inhibitor of LONP1 would result in a compensatory increase in wild type mtDNA, improves heteroplasmy in any cell of claim 25, reduces the ratio of mutated wild type mtDNA in any cell or treats a disorder associated with mutated mtDNA.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims and the nature of the invention:
The claims are drawn to depleting deleterious mitochondrial genomes in any cell type by administering any inhibitor, at its breath, targeted to LONP1 or ATF5; wherein this inhibition would result in a decrease in mutant mtDNA and a increase in mtDNA and further treat any disease associated with mutated mtDNA. The breath of the inhibitor encompasses any nucleic acid, small molecule or derivatives thereof, antibodies, transcription inhibitors or chemical compounds, for example.
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
The state of the prior art:
The prior art teach it was known that siRNA inhibitors and a small molecules such as CDDO were capable of inhibiting expression of LONP1 in cells in vitro (see the 102 rejections above). The prior art of Peter et al. ("Defective mitochondrial protease LonP1 can cause classical mitochondrial disease." Human molecular genetics 27.10 (2018): 1743-1753) describes a defective LONP1 protease can cause mitochondrial diseases such as CODAS syndrome (see page 1744 col. 1) and also teach severe OXPHOS (oxidative enzyme deficiencies) that was observed with a depletion of mtDNA in patient muscles (see 1744 col. 2).
The prior art does not teach inhibition of LONP1 or AFT5 would deplete deleterious mitochondrial genomes in any cell type or result in a decrease in mutant mtDNA and an increase in mtDNA and further treat any disease associated with mutated mtDNA.
The level of one of ordinary skill:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention.
Because the state of the prior art does not provide evidence of the degree of predictability that methods depletion of mutated mtDNA by inhibiting LONP1 or ATF5 would result in the claimed treatments, one of ordinary skill in the art would look for guidance or direction in the instant specification.
The level of predictability in the art:
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03).
The amount of direction provided by the inventor:
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).
The existence of working examples:
The working embodiment in the instant application describes RNAi against LONGp1 in C. elegans decreased mutated mtDNA and an shRNA targeted to ATFs increased heteroplasmy. The working embodiments do not describe using any type of inhibitor targeted to LONP1 or ATF5 would result in a compensatory increase in wild type mtDNA, improves heteroplasmy in any cell of claim 25, reduces the ratio of mutated wild type mtDNA in any cell treat a disorder associated with mutated mtDNA.
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant invention suggests administration of any inhibitor targeted to LONP1 or ATF5 in any cell and treatment of any disease without an enabling disclosure or guidance in the prior art.
While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role LONP1 or ATF5 plays in decreasing mutant mtDNA or treatment of any disease caused by mutant mtDNA. The specification does not provide sufficient guidance and without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
Written Description
Claims 1-3, 5-7, 9-12 and 25-27 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a genus of inhibitors of LONP1 or ATF5 with the function of an increase in wild type mtDNA, improvement of heteroplasmy in any cell, reduction of the the ratio of mutated wild type mtDNA in any cell and treatment of any disorder associated with mutated mtDNA.
The specification describes a RNAi inhibitor and a small molecule CDDO that is capable of targeting LONP1 and ATF5. The specification and claims do not indicate what distinguishing characteristics of these inhibitors described in the specification that are concisely shared by the members of the broad genus comprising any type of inhibitor that would convey to one of skill in the art that these inhibitors represent the entire genus. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination.
Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant comprising a vast number of inhibitors such as antibodies, nucleic acids, small molecules or any derivatives of small molecules such as in claim 8 or chemical compounds, for example, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every inhibitor that has the function of causing a compensatory increase in wild type mtDNA in any cell, improves heteroplasmy in any cell , reduces the ratio of mutated wild type mtDNA in any cell or treating a disorder associated with mutated mtDNA.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636