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
Claims 1-6, 8-17, 21-23 are being considered on their merits. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and applicant’s comments.
Priority
This application is a CON of 16/094,316 (filed 10/17/2018) PAT 11311008 which is a 371 of PCT/US17/28351 (filed 4/19/2017) which claims benefit of 62/324,624 (filed 4/19/2016).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-6, 8-17, 21-23 remain rejected under 35 U.S.C. 103(a) as being unpatentable over Jin (2014, Cryobiology, 68(3): 419-430; 4/21/2022 IDS) in view of Etheridge (2014, Technology, 2(3):229-242; 4/21/2022 IDS) and Ma (2012, Nano Lett., 12:3954-3960) in further view of WO 2007077560 (of record) or WO2005032251.
Regarding claim 1, Jin teaches a method of warming a cryopreserved biospecimen (vitrified oocytes) (page 419, title and abstract).
Jin teaches they conceived the idea that the oocytes could be warmed 100 more rapidly by applying a powerful short duration laser pulse using a laser manufactured by LaserStar Corp. that met their requirements of energy and power (page 420, right column, 2nd full paragraph). Jin teaches there was one important consideration, as the laser emits at 1064 nm in the infrared but the water-rich medium and cell contents absorb only ~3.5% at this wavelength, so they chose to use carbon black (India Ink) that absorbs all wave lengths (page 420, right column, 2nd full paragraph). Regarding claim 1, Jin teaches nearly 100% survival of cryopreserved oocytes via rapid warming using this 1064 nm IR laser pulse (page 419, title).
Regarding claims 1, 11, 13, 15 and 16, Jin teaches a method comprising obtaining a cryopreserved specimen (vitrified oocytes) by suspending in a vitrification solution with a cryoprotective agent such as ethylene glycol or sucrose which permeates the cell, and a laser absorber (such as carbon black/India Ink) and subjecting the cryopreserved specimen to a laser pulse effective to heat the laser absorber sufficiently to rewarm the cryopreserved biospecimen (see pages 420-423, Table 1). Jin teaches the general technology of vitrification in which formation of ice should be avoided with the use of cryopreservatives in order to permeate the cells and convert water to glass preventing ice formation and rewarming should be at a high rate to revert glass to ice. Jin teaches the general premise of the concentration of the cryopreservatives are known in that some permeate the cell and some do not.
Regarding claims 5-6, Jin teaches the cryopreserved specimen is irradiated with laser pulse at wavelength of near infrared radiation (NIR) at 1064 nm (page 420, right column, 2nd full paragraph, line 6++).
Regarding claim 17, Jin teaches the laser pulse produces a warming rate of at least 500,000oC/min (page 421, right column, line 10++).
Jin does not teach the laser absorber comprises a metal/gold nanorod (claims 1-4 and 8), the laser absorbers are injected into the cryopreserved specimen prior to cryopreservation (claims 9-10), the cryopreserved specimen is perfused with the cryoprotective composition (claim 12); however, this would be implicit based on Jin’s teachings that the agent needs to permeate the cell so as to prevent ice formation, the laser absorber is distributed in all compartment of the cell/oocyte (claims 14-15).
Regarding claims 1-4, 9-12 and 14-15, Etheridge teaches heating of metal nanoparticles improves the thawing of cryopreserved biomaterials and that uniformly heating cryopreserved biospecimens can be achieved uniformly loading cryoprotectants to allow for homogeneity in heating (title, abstract and pages 229-230). Regarding claims 1, 9-12 and 14-15, Etheridge teaches both rapid and uniform heating of cryopreserved biospecimens, and that a number of groups have demonstrated various approaches for achieving relatively uniform cryoprotectant distributions within tissues and organs (pages 229-230 and abstract). Specifically, regarding claims 1-4, 9-12 and 14-15, Etheridge teaches uniformly heating cryopreserved biospecimens using mNPs, and in the “Innovation” section of Etheridge on page 229, Etheridge explicitly teaches (1) the mNPs which can be distributed throughout macro- and microscopic tissue structures, (2) that said distribution can likely be accomplished through existing methods for uniformly loading, and (3) that the homogeneity in heating (uniform heating) depends on the mNP distribution. In other words, this page of Etheridge recognizes that uniform heating is beneficial, and that it is directly dependent on mNP distribution (see abstract and pages 229-230). Additionally, regarding claims 1-4, 9-12 and 14-15, Etheridge continues on page 230 to explicitly teach that (1) the uniformity in heating depends on the mNP distribution, wherein the volumetric heating is directly proportional to the local mNP concentration, and (2) a major benefit of nanoparticles is their small size which allows them to achieve relatively uniform cryoprotectant distributions within tissues. Together, these teachings read on the limitation of claim 1 wherein the laser absorbers are distributed throughout the cytoprotective composition such that heating the laser absorbers results in a sufficiently uniform distribution of energy throughout the cytoprotective composition to uniformly rewarm the cryopreserved biospecimen to minimizing damage to the biospecimen.
Regarding claims 1, 9-12 and 14-15, Etheridge teaches both diffusion/perfusion and direct-injection to deliver the nanoparticle into tissue/cells, and provides examples of metal nanoparticles have already been approved for clinical use (page 229 and page 237 at left column, line 5++).
Regarding claims 1-8, Ma is drawn to characterization of gold nanorods irradiated by a 1064 nm NIR laser (Jin’s laser is also a 1064 nm NIR laser) and Ma teaches that gold nanorods beneficially have high heating rates (page 3955 and page 3959 at right column, line 1++, and 1st paragraph++). Regarding claims 1-8, Ma teaches gold nanoparticles can be used with biological material, and that biological material is relatively transparent to NIR light (page 3954 at right column). Regarding claims 1-8, Ma teaches that when gold nanoparticles are irradiated at its surface plasmon resonance frequency, a metallic nanoparticle efficiently converts the absorbed energy into heat that is locally dissipated, thus resulting in a significant temperature increase around the nanoparticle (page 3954 at right column).
WO ‘560 (Gabbai) teaches a process of cryopreserving material and methods of rewarming. Gabbai teaches the general vitrification process. Gabbai teach cryoprotective compositions comprising a biospecimen (see page 19) including cells, organs, (reads on at least 0.1mm) and tissues and methods of using them to preserve biological material, where the composition is contacted with the cellular matter. The composition includes a cryoprotective agent, including a starch or dextran, and a nanostructure, wherein the core material of the nanostructure including metals (page 4, lines 16-18 and page 5, lines 26-29; specifically, page 5, lines 4-6; and 27-29). Gabbai teaches a cryoprotective agent reduces the injury of cells caused by intracellular and extracellular ice crystal formation during freezing and thawing (page 11, lines 12-29). Gabbai teaches Gabbai teaches use of electromagnetic radiation for the thawing and recovery of the material. Gabbai teaches as thawing occurs ice crystals form and increase in size; thus rapid reheating should be done. Gabbai teaches using their cryoprotective composition in a cryopreserved state (pages 19-20). The cryoprotecting agents or nanostructures in the composition may be at a high enough concentration, such that contacting triggers vitrification of the cellular matter. Gabbai teaches concentrations of cryoprotecting agents may range from about 4 M to about 10 M and precise concentrations for each agent can be empirically determined (page 24, lines 10-15). Gabbai is teaches cryoprotecting agents include DMSO, propylene glycol, mannitol, glycerol, polyethylene glycol, ethylene glycol, butanediol, formamide, propanediol and mixtures of these substances. (see page 6, lines 11-22).
WO2005032251 the term "cryopreservation solution" refers to any solution or media in which biological material is immersed before cryopreservation. Typically, cryopreservation solutions contain a balanced salt solution such as phosphate buffered saline and at least one cryoprotectant (as taught by Jin in characterizing the state of the art). Cryoprotectants are substances that reduce the damage incurred by the cells or tissues during freezing and/or thawing. Most freezing solutions are composed of intracellular cryoprotectants (e.g. DMSO, glycerol, ethylene glycol, polyethylene glycol, 1,2- propanediol, formamide) and/or extra cellular cryoprotectants (Sugars, proteins, carbohydrates such as: Hydroxy Ethyl Starch, dextran, etc.). The cryopreservation solution may comprise for example 5 to 200ml of buffered physiological solution and a cell-penetrating organic solute in a concentration from about 0.5M to about 3M. The volume of solution 15 used is such that the tissue would be completely immersed therein and can be easily determined by one skilled in the art and is dependent upon the size of the tissue to be preserved.
It would have been obvious to combine Jin with Etheridge and Ma to inject uniformly distributed gold nanorods as the laser absorber in Jin’s method. A person of ordinary skill in the art would have had a reasonable expectation of success in injecting uniformly distributed gold nanorods as the laser absorber in Jin’s method because Etheridge teaches rapid and uniform heating of cryopreserved biomaterials can be done with direct-injection to deliver the nanoparticle into tissue/cells and Ma establishes that gold nanorods irradiated by a 1064 nm NIR laser (Jin’s laser is also a 1064 nm NIR laser) beneficially have high heating rates. The skilled artisan would have been motivated to use uniformly distributed gold nanorods as the laser absorber in Jin’s method because Etheridge teaches rapid and uniform heating of cryopreserved biomaterials can be done with direct-injection to deliver the nanoparticle into tissue/cells and heating of metal nanoparticles improves the thawing of cryopreserved biomaterials and that uniformly heating cryopreserved biospecimens can be achieved uniformly loading cryoprotectants to allow for homogeneity in heating, while Ma establishes that gold nanorods irradiated by a 1064 nm NIR laser (Jin’s laser is also a 1064 nm NIR laser) beneficially have high heating rates and that gold nanoparticles can be used with biological material. An ordinary skilled artisan would have reasonable expectation of success of achieving such modifications because all of the cited references teach the various steps of the claimed method including use of gold nanorod, etc. is routine and known in the art. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to inject gold nanorod as laser absorber in cryopreserved cells/oocyte to rewarm the cells.
Ma is silent as to the properties of the gold. The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants' gold nanorod, and if so to what extent, from the gold nanorod discussed in Ma. The prior art gold nanorod in the prior art is used for heating by 1064 nm NIR laser, just as the gold nanorod in the claimed method. The cited art taken as a whole demonstrates a reasonable probability that the gold nanorod of the prior art is either identical or sufficiently similar to the claimed gold nanorod that whatever differences exist are not patentably significant. Therefore, the burden of establishing novelty or unobviousness by objective evidence is shifted to applicants.
Additionally it would have been obvious to combine the references and utilize the instantly claimed concentration of the cryopreservative since both WO ‘251 and WO ‘560 teach the state of the art in which cryoprotectants were known substances used to reduce damage incurred by the cells or tissues during freezing and/or thawing and both suggest the claimed concentrations and it is within the purview of a skilled artisan to determine the precise amount.
Response to Arguments
Applicant's arguments filed 2/19/2026 have been fully considered. Applicant’s amendments have necessitated new grounds of rejections addressing the claimed concentration of the cryopreservative. All arguments are directed to the new claim limitations and new claims which have been addressed in the rejection above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-6, 8-17, and 21-23 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7 of U.S. Patent No. 11311008 in view of Etheridge (Technology, 2014, 2(3):229-242, IDS) and Ma (Nano Lett., 2012, 12:3954-3960).
The instant application direct to a method of warming a cryopreserved biospecimen comprising steps of “obtaining…” and “subjecting…”.
Although the conflicting claims are not identical, they are not patentably distinct from each other because both are directed to a method of warming a cryopreserved biospecimen with same steps, wherein the instant application include a laser absorber/plasmonic material that is a gold nanorod that absorbs a narrow band of laser energy by irradiated with visible or near infrared radiation with wavelength between 400-2500 nm, whereas the patent direct to absorber/plasmonic material that is a gold nanorod and a laser pulse sufficient to heat the laser absorber to rewarm the biospecimen. Additionally, the conflicting claims specifically limit to the gold nanorod distributed in the chorion and the yolk.
Patent ‘008 does the properties of the gold nanorod such as the stimulation at near infrared radiation with wavelength between 400-2500 nm and that are injected into the cryopreserved specimen prior to cryopreservation as recited in claims 1 and 9-10, cryopreserved specimen is perfused with the cryoprotective composition (including the claimed cryoprotective species and concentrations) as recited in claim 5-6, 12.
However, Etheridge teaches heating of metal nanoparticles improves the thawing of cryopreserved biomaterials (title and abstract) and diffusion based perfusion of the nanoparticle or in some cases, direct-injection to deliver the nanoparticle into tissue/cells (page 237, left column, line 5++, for claims 9-12 and 14-15). Etheridge teaches heating of metal nanoparticles improves the thawing of cryopreserved biomaterials and that uniformly heating cryopreserved biospecimens can be achieved uniformly loading cryoprotectants to allow for homogeneity in heating (title, abstract and pages 229-230). Regarding claims 1, 9-12 and 14-15, Etheridge teaches both rapid and uniform heating of cryopreserved biospecimens, and that a number of groups have demonstrated various approaches for achieving relatively uniform cryoprotectant distributions within tissues and organs (pages 229-230 and abstract).
Ma teaches gold nanorod irradiated by infrared radiation with wavelength of 1064 nm with high heating rate, and that this allows for peak, or maximal, absorption (page 3959, right column, line 1++, and 1st paragraph++, page 3959, left column and page 3956, left column).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to inject gold nanorod as laser absorber in cryopreserved cells/oocyte to rewarm the cells using infrared radiation with wavelength of 1064 nm with high heating rate.
A person of ordinary skill in the art would have been motivated before the effective filing date of the claimed invention to make the modification because the cited references teaches method of warming a cryopreserved biospecimen using metal nanoparticles and Etheridge teaches rapid and uniform heating of cryopreserved biospecimens (page 229, abstract, line 3++) and suggested direct-injection to deliver the nanoparticle into tissue/cells (page 237, left column, line 5++, for claims 9-12 and 14-15). In addition, it would have been obvious to one skilled in the art to stimulate the gold nanorod in the reference Patent with by infrared radiation with wavelength of 1064 nm as taught by Ma to achieve the predictable result of rapid and uniform heating of cryopreserved biospecimens because Ma establishes that this narrow wavelength stimulates gold nanorods with high heating rate and maximal absorption.
Response to Arguments
Applicant's arguments filed 2/19/2026 have been fully considered but they are not persuasive.
Applicant argues that the new limitations directed to the concentration overcome the rejection. However, US ‘008 claims a cryopreservative (PEG) in the same concentration, i.e. no more than 3M. The rejection is maintained.
Conclusion
All claims are rejected.
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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/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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