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 .
Withdrawn Objections/Rejections
The objection to color drawings, under 37 CFR 1.83(a) because they fail to show a discernment between the two lines in figure 3B as described in the specification. Because the figures are in black and white, one cannot tell which line is Fresh and which line is Fresh + Met, is withdrawn. Applicant submitted a petition for colored drawings that was granted.
The objection to claim 4 is withdrawn. Applicant incorporated the suggested amendment into the claim.
The following rejections of record are modified to take into consideration the amendments to the claims:
Claim Rejections - 35 USC § 112
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 1-6, as amended or originally presented, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, as amended, contains the trademark/trade name “Cryotop®”. 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 carrier and, accordingly, the identification/description is indefinite.
The claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. The terms “an equilibrium treatment” and “a balance treatment duration” are not art recognized terms in English prior art literature.
Claims 2-6 depend upon claim 1. As such, these dependent claims also comprise the above indefinite subject matter.
Response to Arguments
Applicant's arguments filed 1/29/2026 have been fully considered but they are not persuasive.
Applicant submits that the claims have been amended to recite “Cryotop®” which overcome the rejection. In response, “Crypto” with or without the registration mark still is a trademark and therefore has the previously described issues of indefiniteness. See the rejection reiterated above for more detail. As such, the rejection is maintained.
Claim Rejections - 35 USC § 103
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.
(1) Claim(s) 1 and 3-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu (Wu et al. Mol Reprod and Dev (2006) 73:1454-1462) in further view of Leybaert (US 2015/0313208 A1) and Tilly (US 2013/0059384 A1).
Regarding claim 1, Wu teaches an porcine oocyte cryopreservation method. Wu teaches porcine MII-oocytes were initially equilibrated for 5 min in 20% (v/v) ethylene glycol and transferred into the second vitrification medium, that is TCM199 medium containing 40% EG, 0.6 M sucrose. Oocytes were loaded into the narrow end of an open pulled straw (OPS) pipette. Straws were immediately immersed in liquid nitrogen. See paragraph bridging col 1 and 2 of page 1455.
Wu does not teach that the Oocytes were placed in Cryotop carrier before placing in liquid nitrogen, However, Laybert teaches a method of equilibrating oocytes in ethylene glycol and transferring them to vitrification medium in a similar manner to Wu. After transferring to vitrification solution the oocyte were placed in manufactured Cyrtop carriers and transferred immediately to liquid nitrogen. See [0054]. As such, Leybert demonstrates that the use of Cryotop carriers for freezing and storing oocytes was established in the prior art and available for used long before the time of effective filing.
Wu also does not teach a pretreatment step of the oocyte I a medium containing metformin. However, Tilly teaches oocytes can be cultured in the presence of one or more bioenergetic agents prior to cryopreservation. Methods of oocyte cryopreservation are well known in the art. See [0023] and [0282]. Tilly teaches that the bioenergetic agent that can be used prior to the cryopreservation procedure can be metformin. See [0023]). Tilly teaches that the use of the claimed bioenergetic agents can restore the quality of aging oocyte (abstract) and to enhance mitochondrial numbers, mitochondrial activity, cellular energy levels or cellular energy-producing potential in oocytes ([0010]).
As such, it would have been obvious to an artisan of ordinary skill before the time of effective filing: (i) to use the Cryotop carriers taught by Leybert in place of the straw carriers used in the oocyte cryopreservation method of Wu; and (ii) to add a pretreatment step with a medium comprising metformin, as taught by Tilly, to the oocyte cryopreservation method of Wu to predictably arrive at the limitations of claim 1. The artisan would have a reasonable expectation, first, Leybert demonstrates that the Cryotop carriers were commonly and long used to freeze and store oocytes in liquid nitrogen, and second, Tilly states that a bioenergetic agent such as metformin can be used as a pretreatment to oocyte cryopreservation. Further, the artisan would be motivated to add metformin as a pretreatment because Tilly teaches the bioenergetic agent can restore the quality of aging oocyte (abstract) and to enhance mitochondrial numbers, mitochondrial activity, cellular energy levels or cellular energy-producing potential in oocytes. Thus Wu in view of Leybert and Tilly render claim 1 obvious.
Regarding claims 3-4, neither Wu nor Tilly teach that the culture medium comprises 400 µM metformin (claim 3); and neither Wu nor Tilly teach that the pretreatment has a duration of 1 hour (claim 4).
However, MPEP § 2144.05 (II) states the following:
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 reAller, 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 reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
A review of the specification fails to provide evidence that the claimed concentration and pretreatment duration are critical. Absent such evidence it would have been obvious to an artisan of ordinary skill at the time of effectively filing Tilly to try a finite number of possible concentration metformin and a finite number of possible pretreatment durations to predictably arrive at the claimed concentration through routine optimization for use in the oocyte cryopreservation method of Wu. An artisan would have a reasonable expectation of success in optimizing the concentrations and timings because determine optimal concentration and timing were long established in the prior art. Thus, Wu in view of Leybert and Tilly render the claims obvious.
Regarding claim 5, while it is not apparent exactly what is means to the balance treatment duration of the equilibrium treatment, Wu teaches that the oocytes were equilibrated for 5 minutes and then transferred into vitrification medium were load into the straws within 30 seconds of exposure to the medium and immediately placed in liquid nitrogen (paragraph bridging col 1 and 2 on page 1455), suggesting that the teaching of Wu that teach step 2 had a duration of 5-6 minutes, not 3 minutes as claimed.
However, as stated above timing/duration of steps do not support patentability absent evidence of criticality for said timing/duration. As such, it would have been obvious to use routine optimization of the method of Wu to reduce the timing of the equilibration, vitrification, and freezing process taught by Wu from 5-6 minutes down to 3 minutes using routine optimization of Wu. As such, Wu in view of Leybert and Tilly render claim 5 obvious.
(2) Claim(s) 2, as originally presented, is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu (Wu et al. Mol Reprod and Dev (2006) 73:1454-1462), Leybaert (US 2015/0313208 A1) and Tilly (US 2013/0059384 A1) in further view of Ravisankar (Ravisankar et al. Feb 2021 https://bio-protocol.org/exchange/minidetail?id=9096967&type=30).
Wu, Leybaert, and Tilly teach claim 2 as discussed above. These combined arts do not teach that the base medium for the pretreatment step comprises TL, HEPES, and 0.3% BSA.
However, Ravisankar teaches use of TALP as a oocyte base medium comprising Tyrode’s albumin lactate pyruvate and HEPEs buffer to which 0.3% BSA was added (see paragraph).
As such, it would have been obvious to an artisan of ordinary skill at the time of effectively filing to choose TALP-HEPES-BSA, taught by Rasivankar, from a finite number of predictable oocyte base mediums for use in the pretreatment step taught by Wu, Leyaert, and Tilly. The artisan would have a reasonable expectation of success because before the time of effectively filing the TALP-HEPES-BSA medium was being successfully used as a base medium of oocyte collect and other forms of oocyte treatment such as IVF.
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and E are applicable. The claimed method was known in the art at the time of filing as indicated by Wu, Leybaert, and Tilly in further view of Ravisankar. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
(3) Claim(s) 5, as amended, is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu (Wu et al. Mol Reprod and Dev (2006) 73:1454-1462), Leybaert (US 2015/0313208 A1) and Tilly (US 2013/0059384 A1) in further view of Anchamparuthy (Amchamparuthy et al. J Assist Reprod Genet (2009) 26:613-619).
Wu, Leybaert, and Tilly teach claim 5 as discussed above. This combined art does not teach that the vitrification solution is EDFS40 as claimed.
However, Anchamparuthy discloses the oocyte vitrification solution, ES40, made in a Dulbecco’s PBS base medium comprising 40% EG, 18% Ficol-70, and 0.3 M sucrose and FBS.
As such, it would have been obvious to an artisan of ordinary skill at the time of effective filing to choose EFS40 medium, taught by Anchamparuthy, from a finite number of predictable vitrification solutions for use in the oocyte cryopreservation method taught by Wu, Leybaert, and Tilly to predictable arrive at the limitations of claim 6 with a reasonable expectation of success.
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and E are applicable. The claimed method was known in the art at the time of filing as indicated by Wu, Leybaert, and Tilly in further view of Anchamparuthy. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Response to Arguments
Applicant's arguments filed 1/29/2026 have been fully considered but they are not persuasive.
Applicant only address the prior art of Tilly on their remarks and are silents as to the other references used in the rejection. As such, Examiner will conclude that Applicant does not travers their applicability as prior art in the 103 rejections.
Applicant submits the present disclosure and Tilly have different technical purposes. The present disclose aims to reduce mitochondrial temperatures reducing the damage caused to them during freezing and thawing, thereby improving the quality of vitrified oocytes. In contrast, Tilly aims to enhance mitochondrial functions (enhance numbers and activity). Thus the present disclosure and Tilly have essential differences in technical purposes and principles.
In response, Applicant is not considering the breadth of the claims and how the combined prior art teach this breadth. Rejections are not based upon the disclosures but the claims as written. Regardless of whether the Tilly and the instant disclosure and have different technical purpose and principles. The breadth of the claims do not recite anything that distinguishes the claims from Tilly as used in combination with the other cited references. As such, the rejection is maintained.
Applicant submits that the present disclosure and Tilly have different application objects of metformin. The present disclosure applies metformin to oocytes to reduce temperatures in mitochondria to prevent damage. In contrast, Tilly analyzes mitochondrial membrane potential and mitochondrial DNA copy number) of metformin n mouse OSC, which are different from oocytes studies and analyzed in the present disclosure.
In response, Applicant is not considering all of the teachings provided by Tilly and the combined prior art. As stated in the rejection reiterated above, Tilly teaches oocytes can be cultured in the presence of one or more bioenergetic agents prior to cryopreservation. Methods of oocyte cryopreservation are well known in the art. See [0023] and [0282]. Tilly teaches that the bioenergetic agent that can be used prior to the cryopreservation procedure can be metformin. See [0023]). Tilly teaches that the use of the claimed bioenergetic agents can restore the quality of aging oocyte (abstract) and to enhance mitochondrial numbers, mitochondrial activity, cellular energy levels or cellular energy-producing potential in oocytes ([0010]). As such, Tilly does teach treatment of oocyte, not only OSC, with metformin prior to oocyte cryopreservation as required by the claims. The fact that Tilly not look at the same measures of mitochondria is irrelevant because the claims do not recite any measure of mitochondria. As such, any aspect of mitochondrial temperature, number, quality, etc…that may be different between Tilly and the present disclosure does not overcome the rejection of record because the claims limitation are taught by Tilly with the combined cited prior art, with reasonable expectation of success and motivation to combine.
Applicant submits that Tilly lack sufficient embodiments, steps, and data of metformin on oocytes. In response, Tilly is in combination with Wu and other secondary references that teach all the other limitations of the claims. Tilly was provided to teach treating oocytes with metformin and a motivation to do so. No additional embodiments, steps, or data are required by the claims to be taught by Tilly.
Applicant submits that Tilly does not give a technical motivation on concentration of metformin applied on oocytes. Applicant submits that Tilly uses low concentration (25-50 µM) of metformin, not such extra physiological amounts as 400µM as claimed.
In response, most of the claims do not recite thus do not require any particular concentration of metformin. As such, the teachings by Tilly meet the limitations of the claim. Only claim 3 recites 400µM and applicant has not provide any demonstration of criticality of this concentration for the function of the claims as written. As such, Applicant’s argument are not persuasive regarding concentrations differences.
Applicant submits that Tilly has different application scenarios of metformin such as culture medium, retrieval solution, oocyte washing, oocytes, maturation, vitrification solution, cryopreservation solution, and thawing medium. Tilly provides metformin as a bioenergetic agent but does not provide any analysis of effects for applying the metformin in these solution or mediums and does not provide any study or analysis of metformin applies pretreatment of oocytes before cryopreservation.
In response, the fact that Tilly uses metformin in many of the solutions does not negate that Tilly also applies metformin prior to cryopreservation as the claims require. The claims do not recite any further study or analysis of the effect of metformin. As such, the claims do not requires such study or analysis that Applicant suggest makes the method different. The claims are much broader and the teachings of Tilly in combination with the other cited refers to teach and render obvious the claims.
In conclusion, the 103 rejections of record are maintained because the breadth of the claims still are taught by the combined art and the arguments provided in the remarks were not sufficient to overcome the rejections.
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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