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 Claims
Claims 1-4, 6-8, 10-12, 14-15,17-18, 20-23, and 27-28 are pending (claim set as filed on 02/16/2023).
Election/Restrictions
Applicant’s election of Group I, drawn to the method claims, in the reply filed on 12/01/2025 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP 818.01(a)).
Apparatus/device claims 27-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, only method claims 1-4, 6-8, 10-12, 14-15,17-18, and 20-23, are presented for examination.
Priority
This application is a 371 of PCT/IL2021/051009 filed on 08/18/2021, which has a provisional application no.: 63/066,925 filed on 08/18/2020.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 03/18/2024 and 03/04/2025 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Drawings
The drawings filed on 02/16/2023 have been accepted.
Abstract Objection
The abstract of the disclosure is objected to because it does not comply with the proper language and format (see MPEP 608.01(b)). Appropriate correction is required.
Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as “means” and “said” should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns”, “The disclosure defined by this invention”, or “The disclosure describes”, etc.
Claim Rejections - 35 USC §112, Indefinite
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.
Claim 21 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 21 contains the trademark/trade name “Wisconsin” static preservation solution (alternative marketed synonyms include: Viaspan, Servator B, Belzer UW). 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) (MPEP 2173.05(u)). 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 a preservation solution comprising various ingredients such as potassium, glutathione, magnesium, et al., and, accordingly, the identification/description is indefinite as there exists various modified or commercially available versions on the market.
Claim Rejections - 35 USC §103, Obviousness
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 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 non-obviousness.
Claims 1-4, 6-8, 10-12, 14-15, 17-18, and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over She (US 2018/0092348 - cited by the ISA and in the IDS filed on 03/18/2024) in view of Brockbank (US 2018/0192639 A1).
She’s general disclosure relates to the field of cryopreservation and, in particular, relates to compositions and methods for the cryopreservation of biological materials such as cells and tissues (see abstract & ¶ [0002]). Cryopreservation is used for long-time preservation of cells and tissues for cell transplantation, tissue engineering, and regenerative medicine (see ¶ [0003], [0071]). Vitrification is defined by the viscosity of the sample reaching a sufficiently high value to behave like a solid but without crystallization. This glassy state can be induced in most liquids if cooling occurs rapidly. The addition of cryoprotectants can decrease the required high cooling rates (see ¶ [0006], [0076]).
Regarding the contacting with vitrification solution and cryopreserving, She teaches “a method for preserving (e.g., cryopreserving) a biological material. The method may comprise the following steps: (a) combining/mixing/contacting the present preservation composition with a biological material; (b) cooling and/or freezing the mixture; and (c) storing the biological material (e.g., at appropriate storing conditions)” (claim 7) (see ¶ [0016]-[0017], [0047], [0052], [0072], [0113]-[0115]). She teaches mixing freezing solutions with the cell suspension at a 1:1 volume ratio so that the desired working concentration can be obtained (see ¶ [0196]-[0197]: Example 1). “The temperature(s) suitable for freezing or storing the biological material may vary. For instance, cells may be frozen or stored at a temperature ranging from about -70° C to about -200° C. In one embodiment, cells may be frozen or stored at or above the boiling temperature of liquid nitrogen, i.e., at or above about -196°C” (see ¶ [0054], [0072]-[0073]). She further teaches “a non-linear cooling cryopreservation method is achieved by a non-constant cooling rate during at least a portion of the method. In another embodiment, the non-linear cryopreservation method is achieved by a two-step cooling process, wherein the cells or tissue are cooled at a constant or non-constant rate to a first temperature and then subsequently at a constant or non-constant rate to a second temperature (e.g., storage temperature)” (see ¶ [0077]-[0078]).
Regarding claim 8, She teaches lyophilization (see ¶ [0055], [0072], [0150], [0162] which is a freeze-drying procedure under vacuum conditions). Claim interpretation: note that the claims recite the term “optionally” in several occurrences, the MPEP 2111.04 states that “a claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”.
Regarding claim 10, She teaches the cell suspension in the cryopreservation is distributed into cryotubes or cryovials etc., which are then placed in a freezing container (see ¶ [0140]-[0142], which is essentially devoid of air).
Regarding claim 12, She teaches the biological material in the cryopreservation composition is exposed to a temperature less than or equal to -80° C. (e.g., dry ice), less than or
equal to -100° C., -196° C. (e.g., liquid nitrogen), or -205°C. (e.g., slush nitrogen which is a mixture of liquid and solid nitrogen) (see ¶ [0131]).
Regarding claims 20-21 pertaining to the vitrification solution, She discloses cryoprotectants are used to preserve the viability of the cells and tissues during freezing. Commonly used cryoprotectants include glycerol, DMSO, and PEG. Furthermore, some additives, such as macromolecules and sugars, may be added to further decrease the damages on cells and tissues during cryopreservation (see ¶ [0004], [0106]). The cryopreservation solution comprises 0.1-0.5 M of a saccharide (e.g., trehalose), 1-5% of a macromolecule (e.g., albumin) (see ¶ [0008]-[0023], [0031]-[0042], [0059]-[0065], [0089]).
Regarding claim 23 pertaining to thawing and transplanting, She teaches “the method further comprises the step (c) thawing the frozen mixture or the combination of the cryopreservation composition and the biological material” (see ¶ [0019], [0048], [0115], [0150]-[0161]). She teaches “the present preservation compositions and methods, as well as the biological material recovered from preservation using the present preservation compositions and methods can be used for research and/or clinical application (e.g., cell-based therapies, transplantation, regenerative medicine, diagnostics and genetic testing, cell/tissue banking for surveillance, toxicity testing and for in vitro fertilization). (see ¶ [0003], [0170], [0184], [0186]-[0187]).
However, She does not explicitly or expressly teach: the exact claim language pertaining to the temperature and duration limitations (such as seen in claims 1-2, 6, 11-12, 14-15, 17-18, and 22).
Brockbank’s general disclosure relates to the field of cell, tissue, and organ preservation, particularly new ice-free formulations (e.g., for vitrification) incorporating sugars, such as disaccharides (e.g., trehalose and sucrose), and protocols that improve sample material properties and biological viability (see ¶ [0003]-[0006]). Brockbank discloses “a sample to be preserved (e.g., such as a tissue or cellular material) is vitrified when it reaches the glass transition temperature (Tg)” (see ¶ [0032]-[0033]).
The claimed temperature and/or duration conditions would have been readily apparent or prima facie obvious to one of ordinary skill in the art following the guidance of the cited reference because based upon the overall objective provided by She with respect to maximizing the integrity and viability of the biological material for long-term cryopreservation, the adjustments of particular conventional working conditions (e.g., temperature and duration) are deemed a matter of judicious selection and routine optimization which are within the purview of the skill artisan. The disclosure of She establishes the conditions of variable parameters such that one of ordinary skill in the art would recognize that the temperature conditions and duration of exposure are result effective optimizable variables. In particular, She expressly discloses:
“parameters of the freezing step and/or thawing step are optimized such that temperature ramp-up and/or ramp-down rates do not disrupt the integrity of the biological material, and does not adversely affect the viability or function of the biological material post-thaw” (see She at ¶ [0135]).
“a temperature ramp-down phase having a selected rate of temperature reduction. In some embodiments, a rate of temperature reduction in a temperature ramp-down phase is about 10°C per minute, about 1° C per minute, about 2°C per minute, about 5°C per minute, about 7°C per minute, about 12°C per minute, about 15°C per minute, about 17°C per minute, about 20°C per minute” (see She at ¶ [0136]-[0139]).
Furthermore, the secondary reference of Brockbank discloses:
“the cryoprotectant formulations supplemented with sugars (such as trehalose and or sucrose) have a reduced propensity for ice nucleation during exposure to temperatures above the glass transition temperature. Thus, cellular materials in these formulation will tolerate short term exposure to temperatures such as -80°C., for minutes or hours. The precise duration depending upon the cryoprotectant/ sugar formulation. The duration tolerated at each temperature will depend upon the relative cytotoxicity of the cryoprotectant formulation employed at that temperature” (see Brockbank at ¶ [0068]).
“the glass transition temperature of the first solution (such as a cryoprotectant formulation) may be in set at any desired level, such as, for example, in a range of from about -100°C to about -140°C, such as about -110°C to about -130°C, or -115°C to about -130°C” (see Brockbank at ¶ [0069]-[0072]).
Therefore, these are motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Note the MPEP 2144.05(I)(A) states “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. Where 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”. Furthermore, She teaches that a temperature ramp-down phase may include a flash freezing (e.g., maximal temperature reduction) step (see ¶ [0137], which is similar to a rapid freeze step) and also teaches a two-step non-linear cooling step (see ¶ [0077]-[0078]) or a slow-freezing step (see ¶ [0127]-[0130]), which allows for a different temperature exposure similar to a gradual freeze step). Absent any teaching of criticality by the Applicant concerning the temperature or duration, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variables which can be met as a matter of routine optimization (MPEP 2144.05 II), and considering that She is not restricted in the cryopreservation protocol but rather invites modification as “freeze-drying and cryopreservation in accordance with the present disclosure may be carried out in any method suitable to the biological material. The freezing of above methods of the present disclosure can be done in any method or apparatus known in the art” (see She at ¶ [0126]).
Regarding claims 3-4 pertaining to the biological sample, She does not teach wherein said biological sample comprises a tissue or an organ being vascularized, innervated, or both. However, Brockbank teaches a large volume cellular material or sample refers to living biological material containing cellular components, whether the material is natural or manmade and includes cells, tissues and organs (see Brockbank at ¶ [0026]-[0027]); wherein an organ “refers to any organ, such as, for example, liver, lung, kidney, intestine, heart, pancreas, testes, placenta, thymus, adrenal gland, arteries, veins, lymph nodes, bone or skeletal muscle” (see Brockbank at ¶ [0027]-[0028]). Brockbank teaches “the method of any of the above aspects may be a method in which the cellular material is selected from the group consisting of heart valves, skin, tendons and peripheral nerve grafts” (i.e., vascularized or innervated) (see Brockbank at ¶ [0068], [0083], [0090]); and further discloses fingers and limb extremities (see Brockbank at ¶ [0078]). Accordingly, it would have been further obvious to envisage the biological sample being a limb, or a tissue or organ that is vascularized and/or innervated such as taught by Brockbank in the cryopreservation process of She. The ordinary artisan would have had a reasonable expectation of success is because both of the cited references are in the same field of endeavor directed to improvement of long-term cryopreservation protocols of biological materials.
Conclusion
No claims were allowed.
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653