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 .
Status of the Application
Claims 16-35 are pending, of which Claims 25-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 16-24 and 28-35 are under current examination.
Maintained 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.
Claims 16-22, 24, 28, 29, 31-33, 35 and elected species are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Camara ((Drug Discovery today; volume 18, numbers 19/20, 2013, 950-957; as provided by applicant on IDS dated 12/15/2024).
Camara discloses method of treating mtDNA deletion or depletion syndrome due to a defect in POLG2 protein (elected species) comprising administering to the subject deoxyribonucleosides alone or in combination with mtDNA catabolism inhibitors such as EHNA (also equivalent of excipient) (Entire article, especially, abstract; page 954, col 1, last paragraph and col 2, first and second paragraphs; page 956, paragraph 1; Figure 1; and Table 1). Camara discloses that the common feature in all MDDS diseases:
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is depletion of dNTP pool either because of deficient dNTP homeostasis, for example -including caused by defect in POLG 2 protein (elected species), causing reduction in mtDNA replication (see page 953, col 1 and 2; Table 1 as above) or dNTP metabolism (pages 951- 954; Figure1; and Table 1) and may be treated by providing deoxyribonucleosides alone or combination with mtDNA catabolism inhibitors such as EHNA (page 956, col 1, paragraph 1). The cited prior art discloses clinical phenotype MNGIE caused by deficit in protein POLG2 protein (see Table 1 and page 951).
With regard to the limitations “formulated to increase polymerase gamma activity”; “acceleration---polymerization rate”; “formulated for delivery---ophthalmic delivery” -since the cited prior art teaches same method using same treatment composition for treating same disease, the result of such treatment, such as polymerase gamma activity, polymerization rate are expected to increase in the method taught by the cited prior art whether recognized by the cited prior art or not.
Additionally, as the cited prior art teaches same composition as in the instant claims, the composition of the cited prior art must be capable of being “formulated to increase polymerase gamma activity”; and “formulated for delivery---ophthalmic delivery”. Further, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) (“where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81 (preamble is not a limitation where claim is directed to a product and the preamble merely recites a property inherent in an old product defined by the remainder of the claim); STX LLC. v. Brine, 211 F.3d 588, 591, 54 USPQ2d 1347, 1350 (Fed. Cir. 2000).
Since the cited prior art reads on all the limitations of the instant claims 16-22, 24, 28, 29, 31-33 and 35, these claims are anticipated.
Maintained 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 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 of this title, 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 16-24, 28-35 and elected species are rejected under 35 U.S.C. 103 as being unpatentable over Camara ((Drug Discovery today; volume 18, numbers 19/20, 2013, 950-957; as provided by applicant on IDS dated 12/15/2024).
Determining the scope and contents of the prior art
Camara discloses method of treating mtDNA deletion or depletion syndrome due to a defect in POLG2 protein (elected species) comprising administering to the subject deoxyribonucleosides alone or in combination with mtDNA catabolism inhibitors such as EHNA (also equivalent of excipient) (Entire article, especially, abstract; page 954, col 1, last paragraph and col 2, first and second paragraphs; page 956, paragraph 1; Figure 1; and Table 1). Camara discloses that the common feature in all MDDS diseases:
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is depletion of dNTP pool either because of deficient dNTP homeostasis, for example -including caused by defect in POLG 2 protein (elected species), causing reduction in mtDNA replication (see page 953, col 1 and 2; Table 1 as above) or dNTP metabolism (pages 951- 954; Figure1; and Table 1) and may be treated by providing deoxyribonucleosides alone or combination with mtDNA catabolism inhibitors such as EHNA (page 956, col 1, paragraph 1). The cited prior art discloses clinical phenotype MNGIE caused by deficit in protein POLG2 protein (see Table 1 and page 951).
With regard to the limitations “formulated to increase polymerase gamma activity”; “acceleration---polymerization rate”; “formulated for delivery---ophthalmic delivery” -since the cited prior art teaches same method using same treatment composition for treating same disease, the result of such treatment, such as polymerase gamma activity, polymerization rate are expected to increase in the method taught by the cited prior art whether recognized by the cited prior art or not.
Additionally, as the cited prior art teaches same composition as in the instant claims, the composition of the cited prior art must be capable of being “formulated to increase polymerase gamma activity”; and “formulated for delivery---ophthalmic delivery”. Further, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) (“where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81 (preamble is not a limitation where claim is directed to a product and the preamble merely recites a property inherent in an old product defined by the remainder of the claim); STX LLC. v. Brine, 211 F.3d 588, 591, 54 USPQ2d 1347, 1350 (Fed. Cir. 2000).
Ascertaining the differences between the prior art and the claims at issue
Camara teaches applicants process comprising administering deoxyribonucleosides. However, the cited prior art is silent about administering the composition comprising deoxyribonucleosides, i.e. A, T, G and C in equimolar ratio; and Alpers-Huttenlocher syndrome.
Resolving the level of ordinary skill in the pertinent art
With regard to the above difference of Alpers-Huttenlocher syndrome - Although the cited prior art is silent about clinical phenotype Alpers-Huttenlocher syndrome, the cited prior art teaches treating mtDNA deletion or depletion syndrome due to a defect in POLG2 protein (elected species) comprising administering to the subject deoxyribonucleosides alone or in combination with mtDNA catabolism inhibitors such as EHNA. Since the cited prior art teaches treating MDDS caused by same genetic cause and defect in protein as Alpers-Huttenlocher syndrome, it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that any syndrome or phenotype, including Alpers-Huttenlocher syndrome, caused by the same genetic and protein defects taught by the cited prior art may be treated by using method of the cited prior art.
With regard to the difference of administering a composition comprising deoxyribonucleosides A, T, G and C in equimolar ratio (includes T and C in equimolar ratio)- The cited prior art teaches administering deoxyribonucleosides. Since the cited prior art teaches administering all deoxyribonucleosides to restore mtDNA and DNA comprises all 4 deoxyribonucleosides A, T, G and C, it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that a combination comprising all deoxyribonucleosides in equimolar ratio may be administered to the subject.
Based on the above established facts, it appears that the combination of teachings of above cited prior art read applicants’ process.
Considering objective evidence present in the application indicating obviousness or nonobviousness
To establish a prima facie case of obviousness, three basic criteria must be met: (1) the prior art reference must teach or suggest all the claim limitations; (2) there must be some suggestion or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings; and (3) there must be a reasonable expectation of success; and (MPEP § 2143).
In this case, Camara teaches a method of treating mtDNA deletion or depletion syndrome caused by defect in POLG2 comprising administering to the subject deoxyribonucleosides alone or in combination with mtDNA catabolism inhibitors such as EHNA.
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” (Id. At 1395). See MPEP 2143 - Examples of Basic Requirements of a Prima Facie Case of Obviousness [R-9].
In this case at least prong (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success would apply.
The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”KSR, 550 U.S. at ___, 82 USPQ2d at 1397. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. Further, there is a reasonable expectation of success that the composition may comprise all deoxyribonucleosides in equimolar ratio for treating MDDS as taught by the above cited prior art.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited references and to make the instantly claimed process with a reasonable expectation of success.
Response to Arguments
Applicants’ remarks and amendments, as filed on 08/14/2026, have been fully considered but not found persuasive.
Applicant argued over rejection under 102 and 103 that the examiner's basis for the rejection is all MDDS results from impaired dNTP metabolism, however, the cited prior art indicates that POLG2 is associated with defects in mtDNA replication and not associated with defects in DNTP metabolism. Applicant argued that the cited prior art does not teach administration of deoxyribonucleosides to treat MDDS caused by defect in the POLG2 protein. Applicant argued that the cited prior art does not teach or suggest administering all 4 deoxy- ribonucleosides.
This is not found persuasive and the instant claims stand rejected under 102 and 103. This is because The office clearly provided that Camara discloses method of treating mtDNA deletion or depletion syndrome due to a defect in POLG2 protein (elected species) comprising administering to the subject deoxyribonucleosides alone or in combination with mtDNA catabolism inhibitors such as EHNA (also equivalent of excipient) (Entire article, especially, abstract; page 954, col 1, last paragraph and col 2, first and second paragraphs; page 956, paragraph 1; Figure 1; and Table 1). The office also provided that Camara discloses that the common feature in all MDDS diseases:
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is depletion of dNTP pool either because of deficient dNTP homeostasis, for example -including caused by defect in POLG 2 protein (elected species), causing reduction in mtDNA replication (see page 953, col 1 and 2; Table 1 as above) or dNTP metabolism (pages 951- 954; Figure1; and Table 1) and may be treated by providing deoxyribonucleosides alone or combination with mtDNA catabolism inhibitors such as EHNA (page 956, col 1, paragraph 1). The cited prior art discloses clinical phenotype MNGIE caused by deficit in protein POLG2 protein (see Table 1 and page 951). As reinstated above the cited prior art clearly teaches that MDDS disease caused by defects in POLG2 protein is caused by replication in mtDNA, see Table 1. The cited prior art’s additional teaching of other MDDS diseases caused by replication in mtDNA or DNTP metabolism does not preclude the teaching that MDDS disease caused by defects in POLG2 protein is caused by replication in mtDNA and may treated by administration of deoxyribonucleosides alone or combination with mtDNA catabolism inhibitors such as EHNA. Further, contrary to applicant’s argument, the Examiner never said that all MDDS results from impaired dNTP metabolism. In fact, the Examiner provided that “Camara discloses that the common feature in all MDDS diseases:
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is depletion of dNTP pool either because of deficient dNTP homeostasis, for example -including caused by defect in POLG 2 protein (elected species), causing reduction in mtDNA replication (see page 953, col 1 and 2; Table 1 as above) or dNTP metabolism (pages 951- 954; Figure1; and Table 1) and may be treated by providing deoxyribonucleosides alone or combination with mtDNA catabolism inhibitors such as EHNA (page 956, col 1, paragraph 1).” i.e., caused by reduction in mtDNA replication (such as POLG2) or dNTP metabolism.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Conclusion
No Claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PANCHAM BAKSHI whose telephone number is (571)270-3463. The examiner can normally be reached M-Thu 7-4.30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Milligan Adam can be reached at 571-2707674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PANCHAM BAKSHI/Primary Examiner, Art Unit 1623
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