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 Claims
The Office Action is in response to the remarks and amendments filed on 9/26/2025. The objections to the Specification have been in light of the amendments filed. The objection to the claims has been withdrawn in light of the amendments filed. The rejections pursuant to 35 U.S.C. 112(b) have been withdrawn in light of the amendments filed. Claims 3, 11, 14,17, 18, 21-24, and 27-30 are cancelled. Claims 31 and 32 are new. Claims 15, 16, 19, 20, 25 and 26 remain withdrawn. Accordingly, claims 1, 2, 4-10,12, 13, 31, and 32 are pending for consideration in this Office Action.
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.
Claim 1, 2, 4-6, 8-10, 12, 13, 31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz (US3753357A) in view of Rubinsky et al. (US20230189795A1) and Wan (Wan et al. "Time-dependent effects of pressure during preservation of rat hearts in an isochoric system at subfreezing temperatures." CryoLetters 40.1, Jan 2019, [retrieved on 22 Oct 2025], Retrieved from Internet https://www.researchgate.net/publication/332713621_Time-dependent_Effects_of_Pressure_during_Preservation_of_Rat_Hearts_in_an_Isochoric_System_at_Subfreezing_Temperatures).
Regarding Claim 1, Schwartz teaches a method for storing biological material, comprising:
disposing the biological material in a pressure vessel [where a cellular structure 10 is placed in a non-dilatable vessel 14, Figure 2; col 8. lines 10-27];
filling the pressure vessel with a drive liquid [where the non-dilatable vessel is filled with immersion solution 12, Figure 2; col. 8, lines 41-44]
displacing air from the pressure vessel [where cover 18 would be angularly displaced until solution 12 exits from aperture 22; col. 8 line 66 - col. 9, line 5] and sealing the pressure vessel [where hermetic plug 21 would be turned into place; col. 8 line 66 - col. 9, line 5];
providing a mechanically controlled increase in pressure on the drive liquid using a pressure generator [where a piston is on the contained fluid surface and fluid pressure is increased by a constant angular velocity on the vessel cover by a torque wrench; col. 9, lines 42-56] and providing a controlled decrease in temperature to a storage temperature below 00C inside the pressure vessel [where the vessel is brought to -10 degrees Celsius in a controlled bath environment, col. 9, lines 57-67];
wherein at selected temperatures during the controlled decrease in temperature selected pressures are applied to the drive liquid using the pressure generator [where the vessel is brought to 3.9 degrees Celsius and when the vessel reaches a uniform temperature precompression pressure is applied in a controlled manner; col. 9 lines 40-52; and col. 10, lines 10-20] whereby the drive liquid in the pressure vessel is maintained entirely in a stable, liquid state [where pressure is applied linearly to avoid pressure transients throughout the fluid, col. 9, line 48-59; and where the storage is to take place in liquid phase, col. 10, lines 34-40];
wherein freezing of the biological material is prevented at the storage temperature below 00C by maintaining a selected storage pressure to the drive liquid [where at the storage temperature of -10 degrees Celsius the pressure exceeds that which would permit freezing, col. 10, lines 1-15].
Schwartz does not teach wherein:
(a) the mechanically controlled increase in the pressure on the drive liquid is provided in a series of at least two pressure ramping periods, wherein each of the at least two pressure ramping periods comprises a controlled increase in the pressure from a starting ramp pressure to an end ramp pressure with an intermediate pressure soak between each of the at least two pressure ramping periods at a respective end ramp pressure,
(b) the controlled decrease in temperature is provided in a series of at least two temperature ramping periods, wherein each the at least two temperature ramping periods comprises a controlled decrease in the temperature from a starting ramp temperature to an end ramp temperature with an intermediate temperature soak between each of the at least two temperature ramping periods at a respective end ramp temperature, or
(c) both (a) and (b), wherein the intermediate pressure soak and the intermediate temperature soak are performed simultaneously.
However, Rubinsky teaches a process for temperature and pressure controlled cryopreservation of samples [0002] wherein the controlled decrease in temperature [via temperature control unit 50, Figure 10; 0041] is provided in a series of at least two temperature ramping periods [where the biological sample is cooled to an X number of temperatures until subfreezing temperature is achieved where X is an integer greater than 2, Figure 2; 0007], wherein each the at least two temperature ramping periods comprises a controlled decrease in the temperature [where in a first experiment the temperature of the cooling bath starts at 0°C and then set to -5°C and after a 30 minutes was decreased by another -5°C, Figure 2; 0053] from a starting ramp temperature [where the isochoric system were immersed at 0°C, Figure 2; 0053] to an end ramp temperature [where temperature decreased by 5°C, Figure 2; 0053] with an intermediate temperature soak between each of the at least two temperature ramping periods at a respective end ramp temperature [where the cooling bath holds each -5°C decreased temperature for 30 minutes; 0053] where one of ordinary skill in the art would have been capable of applying this known technique to a known device that was ready for improvement and the results would have been predictable to one of ordinary skill in the art i.e., ensuring a stable decrease in temperature and increase in pressure by facilitating thermodynamic equilibrium with a time delay between temperature drops [Rubinsky; 0056].
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of Schwartz to have where the controlled decrease in temperature is provided in a series of at least two temperature ramping periods, wherein each the at least two temperature ramping periods comprises a controlled decrease in the temperature from a starting ramp temperature to an end ramp temperature with an intermediate temperature soak between each of the at least two temperature ramping periods at a respective end ramp temperature in view of the teachings of Rubinsky where this known technique could have been applied to a known device that was ready for improvement and the results would have been predictable i.e., ensuring a stable decrease in temperature and increase in pressure by facilitating thermodynamic equilibrium with a time delay between temperature drops [Rubinsky; 0056].
Schwartz, as modified, does not teach the intermediate pressure soak is at least two hours and the intermediate temperature soak is at least two hours.
However, Wan teaches the effects of pressure and exposure period on rat hearts [Objective, p.1] including an intermediate pressure soak of at least two hours and an intermediate temperature soak of at least two hours [where hearts under isochoric preservation were evaluated at a constant temperature and constant pressure for at least two hours, where optimal hearts experienced a preservation duration of 1 hour, 2 hours, and 6 hours, see optimal line graph of Figure 2; p. 1-2, Results and Discussion] where one of ordinary skill in the art would have been capable of applying routine optimization of a known result effective variable, soak duration, to achieve a recognized result, i.e., providing time to facilitate thermodynamic equilibrium while accounting for specimen damage for a given pressure and temperature and specimen.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of the combined teachings to have where an intermediate pressure soak of at least two hours and an intermediate temperature soak of at least two hours in view of the teachings of Wan where the modification constitutes routine optimization of a known result-effective variable to achieve a recognized result, i.e. providing time to facilitate thermodynamic equilibrium while accounting for specimen damage for a given pressure temperature and specimen.
Regarding Claim 2 Schwartz, as modified, teaches the method of claim 1, and further teaches, disposing the biological material in a sample bag with a preservation solution [where the organ would be wrapped in sterile gauze saturated in Buckley’s or Collins solution and a minimum amount of the solution is introduced into the bag, Figure 2; col. 8, lines 28-44];
evacuating air from the sample bag [where the bag is sealed and evacuated; col. 8, lines 28-44];
and sealing the sample bag [where the bag is sealed and evacuated; col. 8, lines 28-44];
wherein the preservation solution and the drive liquid are maintained in a stable, liquid state [where pressure is applied linearly to avoid pressure transients throughout the fluid in the vessel, col. 9, line 48-59; and where the storage is to take place in liquid phase, col. 10, lines 34-40].
Regarding Claim 4, Schwartz teaches, as modified, the method of claim 2 and further teaches wherein the solution [an isotonically inert and cell compatible medium; col. 7, lines 34-52] comprises a solute that comprises one or more of antifreeze protein, ice binding protein, antifreeze saccharide, ice binding saccharide, ice binding peptide, and other non-colligative agents [where the medium may be Buckley’s solution which is known in the art to comprise non-colligative agent tricresol; col. 7, lines 34-52].
Regarding Claim 5, Schwartz, as modified, teaches the method of claim 2, and further teaches where the solution [an isotonically inert and cell compatible medium; col. 7, lines 34-52] comprises a solute that prevents, inhibits, controls, or sequesters ice crystal growth, and/or prevents nucleation of ice [where the medium may be Buckley’s solution which is known in the art to comprise glycerol; col. 7, lines 34-52].
Regarding Claim 6, Schwartz, as modified, teaches the method of claim 2, wherein the preservation solution [an isotonically inert and cell compatible medium; col. 7, lines 34-52] comprises water and one or more of biological material, soluble molecules, organic and/or inorganic compounds, material in aqueous suspension, aqueous solution, aqueous mixture, aqueous colloids, aqueous-based material, and material of biological origin [where the medium may be Buckley’s solution which is known in the art to comprise water and formaldehyde; col. 7, lines 34-52;].
Regarding Claim 7, Schwartz, as modified, teaches the method of claim 1 and further teaches where decreasing the temperature and increasing the pressure comprises increasing pressure from ambient conditions at 1,000 psig/minute (6.9 MPa) in increments of 200 psig (1.4 MPa) [where the pressure is applied in a controlled manner, at a rate of 1,000 psig or less per minute with pressure being increased linearly; col. 9, lines 46-57] and decreasing the temperature comprises decreasing the temperature from ambient conditions to -22°C [where temperature is reduced to a temperature less than 0 °C and more than -22 °C, Claim 12], but Schwartz does not teach increasing pressure to 30,000 psig (207 MPa) over the at least two ramping periods during which pressure is increased.
However, Rubinsky teaches a process for temperature and pressure controlled cryopreservation of samples [0002] including increasing pressure to 30,000 psig (207 MPa) [where pressure increases from ambient pressure to 2070 bar (207 MPa), met between the 1870 bar and 2160 mark, Figure 2; 0056] over the at least two ramping periods during which pressure is increased [over four ramping periods: 0 bars to 1077 bars, 1077 bars to 1502 bars, 1502 bars to 1870 bars, and 1820 bars to 2160 bars, Figure 2; 0056] where one of ordinary skill in the art would have been capable of applying this known technique to a known device that was ready for improvement and the results would have been predictable to one of ordinary skill in the art i.e., ensuring a stable decrease in temperature and increase in pressure by facilitating thermodynamic equilibrium with a time delay between temperature drops [Rubinsky; 0056].
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of the combined teachings to include increasing pressure to 30,000 psig (207 MPa) over the at least two ramping periods during which pressure is increased in view of the teachings of Rubinsky where this known technique could have been applied to a known device that was ready for improvement and the results would have been predictable i.e., ensuring a stable decrease in temperature and increase in pressure by facilitating thermodynamic equilibrium with a time delay between temperature drops [Rubinsky; 0056].
Regarding Claim 8, Schwartz, as modified, teaches the method of claim 1 and further teaches where the biological material comprises one or more of organic molecules, molecular complexes, nucleic acids, saccharides, amino acids, peptides, proteins, enzymes, organelles, organoids, cells, tissues, organs, organisms [where specimens may be cell structures as varied as cornea, kidneys, tissues, bone marrow, bone, brain cells, enzymes, sera, and comestibles; col. 7, lines 34-51] and an aqueous solution [where cells are known to be composed of five basic substances: including electrolytes dissolved in water; col. 1, lines 58-65].
Regarding Claim 9, Schwartz, as modified, teaches the method of claim 1 and further teaches the biological material comprises cells, tissues, organs, or entire organisms [where specimens may be cell structures as varied as cornea, kidneys, tissues, bone marrow, bone, brain cells, enzymes, sera, and comestibles; col. 7, lines 34-51].
Regarding Claim 10, Schwartz, as modified, teaches the method of claim 1 and further teaches where the storage temperature is from -5°C to -22°C or the storage temperature is -22°C [where the storage temperature may take place between -15 °C and -20 °C and freezing will not take place in most cells until -22 °C; col. 10, lines 1-15]
Regarding Claim 12, Schwartz, as modified, teaches the method of claim 1 and further teaches the storage temperature and applied storage pressure prevent freezing and cell damage by maintaining cells in a metastable supercooled liquid state [col. 10, lines 1-20].
Regarding Claim 13, Schwartz, as modified, teaches the method of claim 1 and further teaches where the drive liquid [immersing solution 12, Figure 2] comprises propylene glycol, ethylene glycol, oil, petroleum, fish oil, mineral oil, vegetable oil, water, or seawater, or any combination thereof [where immersing solution 12 may be distilled water treated with ioclide; col. 10, lines 40 - 44].
Regarding Claim 31, Schwartz, as modified, teaches the method of claim 1 and does not teach the intermediate pressure soak and the intermediate temperature soak are at least 4 hours or at least 6 hours.
Wan teaches the effects of pressure and exposure period on rat hearts [Objective, p.1] where the intermediate pressure soak and the intermediate temperature soak are at least 4 hours or at least 6 hours [where hearts under isochoric preservation were evaluated at a constant temperature and constant pressure for at least two hours, where optimal hearts experienced a preservation duration of 1 hour, 2 hours, and 6 hours, see optimal line graph of Figure 2; p. 1-2, Results and Discussion], where one of ordinary skill in the art would have been capable of applying routine optimization of a known result effective variable, soak duration, to achieve a recognized result, i.e., extending preservation time while accounting for specimen damage for a given pressure and temperature and specimen.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of the combined teachings to have where the intermediate pressure soak and the intermediate temperature soak are at least 4 hours or at least 6 hours in view of the teachings of Wan where the modification constitutes routine optimization of a known result-effective variable to achieve a recognized result, i.e. extending preservation time while accounting for specimen damage for a given pressure temperature and specimen.
Regarding Claim 32, Schwartz, as modified, teaches the method of claim 1 and does not teach where the mechanically controlled increase in pressure on the drive liquid is provided in a series of from 2 to 6 pressure ramping periods and/or the controlled decrease in temperature is provided in a series of from 2 to 6 temperature ramping periods.
However, Rubinsky teaches a process for temperature and pressure-controlled cryopreservation of samples by using isochoric systems [0002] where the controlled decrease in temperature [via temperature control unit 50, Figure 10; 0041] is provided in a series of from 2 to 6 temperature ramping periods [where the biological sample is cooled to an X number of temperatures until subfreezing temperature is achieved where X is an integer greater than 2, Figure 2; 0007] where one of ordinary skill in the art would have been capable of applying this known technique to a known device that was ready for improvement and the results would have been predictable to one of ordinary skill in the art i.e., ensuring a stable decrease in temperature and increase in pressure by facilitating thermodynamic equilibrium with incremental temperature changes [Rubinsky; 0033]
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of the combined teachings to have where the controlled decrease in temperature is provided in a series of from 2 to 6 temperature ramping periods in view of the teachings of Rubinsky where this known technique could have been applied to a known device that was ready for improvement and the results would have been predictable i.e., ensuring a stable decrease in temperature and increase in pressure by facilitating thermodynamic equilibrium with incremental temperature changes [Rubinsky; 0033].
Response to Arguments
Applicant preemptively argues on page 11 of the remarks filed 9/26/2025 that Schwartz fails to anticipate each and every limitation of claims 1-2, 4-6, 8-10 and 12-13 under 35 U.S.C. 102(a)(1) because independent claim 1, as amended, requires (a), (b) or (c). Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant further argues on page 13 of the remarks in regard to the 35 U.S.C. 103 rejection of Claim 7 over Schwartz in view of Hoffman that the combined teachings fail to teach, suggest, or disclose claim 7, as amended, and is silent regarding added limitations of independent claim 1. Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant does not separately argue the rejection of claims 2-6 and 9 except for their dependence upon claim 1. Accordingly, the rejections of record are considered proper and remain.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Nunn, J.H., et al., “The development of formocresol as medicament for primary molar pulpotomy procedures.” in: Journal of Dentistry for Children, 1996. pp. 51. describes the standard formulation of Buckley’s solution, also known as formocresol, and confirms formaldehyde, tricresol, glycerol, and water are normally included in the formulation.
The Examiner notes that the withdrawn claims 15, 16, 19, 20, 25 and 26 may be eligible for rejoinder if the elected claims (1, 2, 4-10, 12,13, 31 and 32) are found allowable. Applicant is encouraged to review and amend the withdrawn claims as appropriate maintain consistency with allowable subject matter and facilitate potential rejoinder.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/KEONA LAUREN BANKS/Examiner, Art Unit 3763
/ELIZABETH J MARTIN/Primary Examiner, Art Unit 3763