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/Restriction
Claims 1-4, 7, 9, 11, 16, 20-23, 25, 27, 29, 31, 40, and 78 are pending
Applicant’s election without traverse of Group I, 1-4, 7, 9, 11, 16, 20-23, 25, 27, 29 and 31 in the reply filed on 07/14/2026 is acknowledged.
Claim 40 and 78 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/14/2026
Claims 1-4, 7, 9, 11, 16, 20-23, 25, 27, 29 and 31 have been examined on their merits.
Claim Interpretation
Claim 1 recites “freezing . . . corneal endothelial cells and/or . . . corneal endothelium-like cells in a non-frozen state. The plain language of the clause could imply that the cells are somehow frozen in a non-frozen which is an impossibility. However, based on the context of the claims (the claim also states “when changing the temperature from a non-frozen temperature to a freezing target temperature”), the disclosure, and the state of the art, it appears that Applicant intends for the clause to mean freezing cells which are in a non-frozen state prior to the freezing process (i.e., from a non-frozen state) which is how the claim has been interpreted.
Additionally, it is noted that It is noted that in regards to the word “about” the instant specification explicitly defines this term to mean “±10%” (paragraph [0206]).
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 (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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 7, 9, 11, 16, 21-22, 27, and 31 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Eskandari et al. (WO2020037416A1, on IDS 01/15/2026) as evidenced by Ross et al. (Cryobiology, 2010) and Ashrafi et al. (Cryobiology, 2025).
In regards to claims 1, 7, 9, Eskandari discloses methods for cryopreserving (freezing) cells including corneal endothelial cells(claims 1 and 3). Eskandari discloses that cells are cooled (frozen) at a rate between 0.2°C/min and 1°C/min (claim 10), which overlaps with the claimed range of less than 1°C/min (or about 0.1°C/min to about 0.9°C/min as in claim 7; a rate of about 0.7°C/min or less as in claim 9).
In regards to claim 2, Eskandari discloses that the method can cryopreserve cells for long periods of time (thus, maintenance) (paragraphs [002, 00119]).
In regards to claims 3 and 4, Eskandari discloses that the cells can be maintained at temperatures as low as -196°C (paragraph [002, 00119]), which overlaps with the claimed ranges.
In regards to claim 11, Eskandari discloses that the portion of the freezing (which is less than 1°C as discussed above) occurs over temperature ranges that overlaps with the temperatures ranges of about -20° ± 10°C (Fig. 1).
In regards to claim 16, Eskandari discloses that the cells can be cryopreserved in a solution comprising 5% DMSO (claim 27), which overlaps with the claimed ranges.
In regards to claims 21 and 27, Eskandari discloses that corneal endothelial cells were cooled to -40 °C (a first target temperature) at a rate of 0.2 °C/min (a first target rate, and which overlaps with the claimed ranges) (paragraph [00111]). Following this, Eskandari teaches that the samples were “plunged” (thus to a second target temperature) into liquid nitrogen (paragraph [00111]). As evidenced by Ross-Rodriguez, plunging is a technique in the art wherein after initial cooling, to a target temperature the rate of increases once the cells are put in liquid nitrogen which are then cooled down to -196°C (which is noted is the boiling point of nitrogen) (see Fig. 1, 40). Thus, the plunging step of Eskandari results in a second target temperature at a second target rate wherein the first target rate is less than 1°C and slower than the second rate as claimed.
In regards to claim 22, Eskandari discloses that during freezing, the freezing is interrupted at various temperatures (i.e., target temperatures; paragraphs [0072, 00109]); Fig. 1). As evidenced by Ashrafi, interruption is a well-known cryopreservation technique wherein cells are cooled to a sub-zero temperature and held (maintained) at that temperature for some time (Cooling profile, p5).
In regards to claim 31, it is noted that this is an independent claim. In regards to the limitations of the claim, as discussed above, Eskandari discloses methods for cryopreserving (freezing) cells including corneal endothelial cells (claims 1 and 3). Eskandari discloses that cells are cooled (frozen) at a rate between 0.2°C/min and 1°C/min (claim 10), which overlaps with the claimed range of less than 1°C/min. As above, Eskandari teaches that the cells can be frozen to temperatures as low as -196°C (paragraph [002, 00119]), and therefore, the rate refers to changing the temperature from a non-frozen temperature to a freezing target temperature as claimed.
Therefore, Eskandari discloses the invention as claimed.
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 29 is rejected under 35 U.S.C. 103 as being unpatentable over Eskandari et al. (WO2020037416A1, on IDS 01/15/2026).
Eskandari anticipates claims 1 and 21 as discussed above.
In regards to claim 29, as discussed above, Eskandari teaches that corneal endothelial cells were cooled to -40 °C (a first target temperature) at a rate of 0.2 °C/min (a first target rate, and which overlaps with the claimed ranges) (paragraph [00111]). Following this, Eskandari teaches that the samples were “plunged” (thus to a second target temperature) into liquid nitrogen (paragraph [00111]). As above, this results in a second target temperature at a second target rate wherein the first target rate is less than 1°C and slower than the second rate as claimed. Thus, Eskandari teaches at least first and second targets and that cells can be frozen at different rates.
However, regards to claim 29 specifically, the claim requires a second rate of about 0.5°C to about 5°C or a second rate of about 1°C to about 3°C. It is noted that plunging results in a rate of colling that is fold greater than the claimed range (see Ross-Rodriguez, Fig. 1, p40, Fig. 2, p41). Therefore, the specific rates in claim 29 refer to a step other than plunging.
However, as above, Eskandari teaches that cell samples were interrupted at various temperatures including -10, -20, -30, -40 and -50°C (paragraphs [0072, 00109] [0072]; Fig. 1). Continuing, Eskandari teaches that the resulting decreases in viability was particularly noticeable at -10 °C when the PCECs (corneal epithelial cells) were cooled at a faster rate (1 °C/min compared to 0.2 °C/min), but that when tested at lower interruption temperatures (-30, -40 and -50 °C), the relative and absolute viabilities were mostly over 90%, with no significant statistical difference between cooling at 0.2 °C/min vs. 1 °C/min (p > 0.05) (citing Figs. 5A and 5B; paragraph [00109]).
Therefore, a person of ordinary skill in the art would have been motivated to use a decreased rate of cooling (e.g., 0.2 °C/min) covering a first target temperature of 10°C because the decreased rate would promote cell viability (see Figs. 5A and 5B of Eskandari). They would be motivated to increase the rate of cooling after this first target temperature (e.g., 1°C/min, which overlaps with the claimed range) in order to save time. Furthermore, because Eskandari teaches that corneal epithelial cells can be cultured under a range of freezing rates, all of which overlap with the claimed ranges, because as taught by Eskandari the rates of freeing can change, a person of ordinary skill in the art could have modified the method of Eskandari and included a second target rate that is greater than the first target rate and that overlaps with the claimed ranges with predictable results and a reasonable expectation of success.
Therefore, the teachings of Eskandari render obvious the invention as claimed.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Eskandari et al. (WO2020037416A1, on IDS 01/15/2026) view of Tocris (ROCK inhibitor for Stem Cell Cryopreservation, 2019).
Eskandari anticipates claims 1 as discussed above.
In regards to claim 20, Eskandari does not explicitly teach that the freezing occurs in the presence of a ROCK inhibitor.
However, it would have been predicably obvious to add a ROCK inhibitor because as taught by Tocris, it is known in the art that ROCK inhibitors can be added to improve cell viability during cryopreservation (ROCK inhibitor for cryopreservation, first and second pages; Fig. 1, second page).
Therefore, the combined teachings of Eskandari and Tocris renders the invention unpatentable as claimed.
Claims 23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Eskandari et al. (WO2020037416A1, on IDS 01/15/2026) view of Ross-Rodriguez et al. (Cryobiology, 2010).
Eskandari anticipates claims 1 and 21 as discussed above.
In regards to claims 23 and 25, in regards to a second target temperature, as above, Eskandari teaches that the cells can be maintained at temperatures as low as -196°C (paragraph [002, 00119], again, the boiling point of liquid nitrogen), which overlaps with the claimed ranges.
In regards to the first target temperature, in embodiments, Eskandari teaches that the cryopreservation can be interrupted at different temperatures including -10, -20, -30, -40, and -50 °C (paragraphs [0072, 00109] [0072]; Fig. 1), which overlaps with the claimed ranges.
While in embodiments, the cells are cooled to -40°C (a first target temperature) before plunging (paragraph [0073]), which is higher than a temperature range of about -20°C to about -5°C or about -15°C to about -10°C, a person of ordinary skill in the art could have arrived at these first temperature ranges by routine optimization (see MPEP 2144.04(II)).
Indeed, the disclosure does not test differences in first target temperatures, but rather only performs a first target temperature of about -10°C (see Figs. 30 and 31) and contains prophetic disclosure of first target temperatures (see paragraphs [0029]). Therefore, there is no indication in the disclosure that the temperature range is critical as required by MPEP2144.04(II) (Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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 Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”).
In the instant case, because Ross-Rodriguez demonstrates that can be cryopreserved with first target temperatures ranging from -3°C to at least -20°C (Fig. 2, p41), which overlap with the claimed ranges, and because as above, Eskandari teaches that freezing can be interrupted over a rage of temperatures (from -10, -20, -30, -40, and -50°C; paragraphs [0072, 00109] [0072]; Fig. 1), which also overlaps with the claimed ranges, a person of ordinary skill in the art could have arrived at the claimed first target temperature range by routine optimization with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Eskandari and Ross renders the invention unpatentable as claimed.
Conclusion
No claims are allowed.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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