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
Applicant's request for reconsideration of the finality of the rejection of the last Office action is persuasive and, therefore, the finality of that action is withdrawn.
This Office Action is responsive to Applicant’s After Final, filed January 23, 2026. The amendment, filed January 23, 2026, is entered, wherein claims 1 and 18 are amended and claims 7 – 8, 17, and 19 are canceled.
Claims 1 – 6, 9 – 16, 18, and 20 – 22 are pending in this application and are currently examined.
Priority
3. This application is a domestic application, filed January 20, 2022, which claims benefit of provisional application 63/139,437, filed January 20, 2021.
Response to Applicant’s Remarks:
Applicant amended claims 1 and 18 for reciting “respiratory enzyme complex I” has been fully considered and are found to be supported by the provisional application. Therefore, the priority date of claims 1 – 6, 9 – 16, 18, and 20 – 22 is January 20, 2021.
Withdrawn Rejections
4. The rejection of claims 1 – 6, 9 – 16, 18, and 20 – 22 in the previous Office Action, mailed October 29, 2025, 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inventor(s), at the time the application was filed, had possession of the claimed invention has been considered and is withdrawn in view of the amended claims 1 and 18.
The rejection of claims 1 – 2, 4 – 6, 10 – 11, 13 – 16, and 18 in the previous Office Action, mailed October 29, 2025, under 35 U.S.C. 102(a)(1) as being anticipated by Zheng et al. has been considered and is withdrawn in view of the amended claims 1 and 18 as the amendment is now being supported by the provisional application.
The rejection of claims 1 – 6, 9 – 16, 18, and 20 – 22 in the previous Office Action, mailed October 29, 2025, under 35 U.S.C. 103 as being unpatentable over Zheng et al. in view of Temofeew has been considered and is withdrawn in view of the amended claims 1 and 18 as the amendment is now being supported by the provisional application.
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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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 1 – 3, 9 – 10, 12, 15 – 16, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Kazezian et al. (Applied Sciences, 2020, Vol. 10, Issue 18, Reference included with PTO-892) in view of Chen et al. (Cell Death and Disease, 2016, Vol. 7, Issue 10, Reference included with PTO-892).
a. Regarding claims 1 – 3, 9 – 10, 12, 15 – 16, and 18, Kazezian et al. teach that intervertebral disc (IVD) degeneration is a leading cause of low back pain worldwide. In the last few decades, hyaluronic acid (HA) has popularized due to its anti-inflammatory, analgesic and extracellular matrix enhancing properties. Thus, there is expressed interest in treating the IVD degeneration using different HA compositions. An ideal HA-based biomaterial needs to be compatible and supportive of the disc microenvironment in general and inhibit inflammation and downstream cascades leading to the innervation, vascularization and pain sensation in particular (Abstract). The following figure disclose the administration of HA hydrogel for treating IVD degeneration (page 2, Figure 1):
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There are some studies report that the hydrophilic properties of HA is able to restore disc height (page 13, para. 2). Kazezian et al. disclose that the biochemical properties of the HA molecule are entirely dependent on its size (page 5, para. 2). High molecular weight (HMW) HA is capable of inhibiting the signaling of inflammatory cytokines and matrix-degrading enzymes (page 6, para. 2). A study discloses that use of various combinations of HMW HA and processing techniques can reduce inflammation, innervation, and pain in the disc (page 13, para. 5; page 14, para. 1). For example, HMW HA might have a molecular weight of 2 – 4 x 106 Da (page 4, para. 3). Another study disclosed by Kazezian et al. finds that re-herniation is deferred successfully by using HA/collagen hydrogel (page 9, Table 2). Therefore, HA-based injectable hydrogels are strong candidates as effective treatments for disc degeneration (page 14, para. 6). Moreover, Kazezian et al. disclose that studying IVD degeneration using human subjects is challenging, thus, different animal models emerged (page 6, para. 3).
However, Kazezian et al. do not teach the method comprises administering amobarbital, adenosine diphosphate ribose, or metformin.
Chen et al. teach that IVD degeneration is a complicated process that involves both cellular apoptosis and senescence. The effect of metformin on IVD degeneration is investigated both in vitro and in vivo. The study shows that metformin attenuated cellular apoptosis and senescence induced by tert-butyl hydroperoxide in nucleus pulposus cells. In vivo study illustrates that metformin treatment could ameliorate IVD degeneration in a puncture-induced rat model. Thus, the study shows that metformin could protect nucleus pulposus cells against apoptosis and senescence via autophagy stimulation and ameliorate disc degeneration in vivo, revealing its potential to be a therapeutic agent for IVD degeneration (Abstract).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine hyaluronic acid as taught by Kazezian et al. with metformin in view of Chen et al. for treating IVD degeneration because Kazezian et al. teach that hyaluronic acid is a strong candidate as an effective treatment for disc degeneration and Chen et al. teach that metformin is a potential therapeutic for IVD degeneration. It would have been obvious for one of ordinary skill in the art to combine hyaluronic acid as taught by Kazezian et al. with metformin in view of Chen et al. because both hyaluronic acid and metformin are known separately in the prior art for the purpose of treating IVD degeneration, and it would have been obvious to combine them to treat the same disease. For the molecular weight of HA, Kazezian et al. suggest that HMW HA has been tested and has found promising effects on reducing pain on the disc, wherein Kazezian et al. define HMW HA as HA having 2 – 4 x 106 Da, which is 2 – 4 MDa. The disclosure of Kazezian et al. reads on the limitation of claim 3. Although Kazezian et al. do not disclose the exact disc the hyaluronic acid is injected, Kazezian et al. disclose that low back pain is an medical condition affecting people worldwide. It is expected that the injection may be administered to the lumbar disc to ease low back pain. Finally, the combination of Kazezian et al. and Chen et al. will yield the claimed method, wherein the limitation “reduces reactive oxygen species (ROS) production in the nucleus pulposus” of claim 10 will necessarily be achieved. One of the ordinary skill in the art would have had a reasonable expectation of success to combine hyaluronic acid as taught by Kazezian et al. with metformin in view of Chen et al. because it is well known to combine drugs to treat the same disease. Claims 4 – 6, 11, 13 – 14, and 20 – 22 are rejected under 35 U.S.C. 103 as being unpatentable over Kazezian et al. (Applied Sciences, 2020, Vol. 10, Issue 18, Reference included with PTO-892) in view of Chen et al. (Cell Death and Disease, 2016, Vol. 7, Issue 10, Reference included with PTO-892) as applied to claims 1 – 3, 9 – 10, 12, 15 – 16, and 18 above, and further in view of Davis et al. (US10279079B2).
b. Regarding claims 4 – 6, 11, 13 – 14, and 20 – 22, the references teach the limitations discussed above.
However, these references do not teach the amount of hyaluronic acid in the composition. These references do not teach the composition further comprises a poloxamer and the amount of poloxamer. These references do not teach the composition is a thermoresponsive hydrogel. These references do not teach the mammal has an injury in the nucleus pulposus.
Davis et al. teach biocompatible composition comprising a poloxamer and one or more additives, such as hyaluronic acid for the repair of an injured spinal disc (Abstract). The biocompatible composition includes HA-gelatin-containing poloxamer hydrogel. This hydrogel is liquid at low temperatures and transition to a gel/solid phase at higher temperatures (Col. 2, lines 46 – 50). The composition comprising 0.2 – 1.0 % w/v hyaluronic acid and 20% w/v poloxamer (Col. 3, lines 40 – 44). Davis et al. teach that the method for treating a spinal disc injury in patient can include the step of removing nucleus pulposus tissue one or more of the patient’s spinal discs, thereby, creating an implantation site, and providing a composition to the implantation site (Col. 12, lines 31 – 36). Davis et al. further teach that a method for repairing a spinal disc comprises applying the biocompatible composition to the area of a damaged spinal disc (claim 12).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the combination of hyaluronic acid and metformin as taught by Kazezian et al. and Chen et al. with poloxamer in view of Davis et al. for treating IVD degeneration because Kazezian et al. and Chen et al. teach that hyaluronic acid and metformin are potential therapeutics for treating IVD degeneration and Davis et al. teach that the composition of poloxamer and hyaluronic acid may be used to repair damaged spinal disc. One would have been motivated to combine the combination of hyaluronic acid and metformin as taught by Kazezian et al. and Chen et al. with poloxamer in view of Davis et al. for treating IVD degeneration because it is known in the art that IVD degeneration will lead to damaged spinal disc. It would have been obvious for one of ordinary skill in the art to combine the combination of hyaluronic acid and metformin as taught by Kazezian et al. and Chen et al. with poloxamer in view of Davis et al. for treating IVD degeneration because hyaluronic acid, metformin, and poloxamer are known in the prior art for treating IVD degeneration-related conditions, and it would have been obvious to combine drugs known to treat the same condition. One would have been motivated to incorporate the thermoresponsive property to the hydrogel as taught by Davis et al. because this property allows easy injection at low temperature and would transition to solid phase to support the spinal cord when inside the body. Davis et al. teach the method of treating spinal disc injury, wherein the method disclosed is a surgery with immediate administration of the composition, which reads on the limitation of claim 11. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success to combine the combination of hyaluronic acid and metformin as taught by Kazezian et al. and Chen et al. with poloxamer in view of Davis et al. for treating IVD degeneration because it is well known to combine drugs to treat the same medical conditions.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed January 23, 2026, has been fully considered.
Applicant argues that Zheng et al. was publicly available after the priority date of the instant claims and thus cannot be considered as prior art. The examiner acknowledges the argument and has withdrawn the previous 102 and 103 rejections.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693