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 .
Claims 1,3-12,14-15 are under examination.
Response to Applicant’s Arguments/Amendments
The claim amendments dated February 11, 2026 have significantly altered the scope of the invention. As a result of the amendments, the former rejections are withdrawn and new rejections put forward. Applicants also argue that Jennings teaches “sodium lithocholate chenocholate” and not –sodium lithocholate--. While sodium lithocholate is a recognized compound, sodium lithocholate chenocholate is not recognized as a chemical compound. It appears that there are typos in Jennings and a comma is needed after the term “sodium lithocholate”; “sodium lithocholate” is still disclosed by Jennings. The past rejection citing Gibson had a typo that referred to Gibson as Gordon; the cited paragraphs are from the Gibson reference.
The examiner would like to further point out that both cryopreservation and lyophilization involving freezing processes, therefore, an artisan would have been motivated to have interchanged components from a cryopreservation process/medium and a lyophilization process/medium and vice versa because such components protect biological specimens during freezing processes.
The instant set of claims are so broad and include the transition term comprising which means that other active protective agents can be present. If it is the intent of applicants to focus on the bile salts being the only protective agent in the claim language, then amending the claims to recite this would help get around the references cited in the current rejections.
Applicants argue that the use of Xu in the rejections is improper because Xu does not teach a cryopreservation solution with bile salts. The primary reference is relied upon for teaching a cryopreservation solution with bile salts. Xu is only being relied upon to teach administration of the cryopreservation solution to a biological substrate using a drip method. Xu is applied in the rejection to teach a method of administration, not a cryopreservation medium with bile salts.
Claim Rejections - 35 USC § 102
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.
Claims 1,3-4,8-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim (KR102116954)
Kim discloses cryopreserving a biological substrate including at least one of cryopreserved biological cells; and applying a bile salt to the cryopreserved biological substrate before and/or during cryopreservation of the biological substrate/cells (Pages 1-3 of Kim); wherein the bile salt is selected from the group consisting of sodium cholate (NaC) and sodium deoxycholate (NaDC) (Page 3, 2nd paragraph of Kim), and is provided in a solution that does not include glycerol or dimethyl sulfoxide (Page 3, 1st paragraph of Kim) as in instant Claim 1. Kim discloses wherein the bile salt is dissolved in a solvent to form the solution and the solution is applied to the cryopreserved biological substrate (Page 2, Means for Solving the Problem, 3rd Paragraph; Page 3, 2nd Paragraph) as in instant Claim 3. Kim discloses wherein the solvent comprises phosphate-buffered saline (PBS) (Page 2, Means for Solving the Problem, 3rd Paragraph) as in instant Claim 4. Kim discloses wherein the bile salt is applied to the biological substrate before/during cryopreservation of the biological substrate (Page 1, Background Art, Paragraph 3; Page 3, 2nd Paragraph) as in instant Claim 8-9. Kim discloses wherein the bile salt is applied to the biological substrate by immersing the biological substate in a solution containing the bile salt (Page 1, Background Art, Paragraph 3; Page 3, 2nd Paragraph) as in instant Claim 10.
The reference anticipates the claim limitations
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.
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.
Claims 1,3-5,8-10,12,15 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (KR102116954)
Kim applies as above to teach claims 1,3-4,8-10. Kim discloses cryopreserving a biological substrate including at least one of cryopreserved biological substrate/cells and applying a solution containing a bile salt to the cryopreserved biological substrate/cells before and/or during cryopreservation of the biological substrate/cells (Pages 1-3 of Kim). Kim discloses wherein the bile salt is selected from the group consisting of sodium cholate (NaC) and sodium deoxycholate (NaDC) (Page 3, 2nd Paragraph) and the bile salt is provided in a solution that does not include glycerol or dimethyl sulfoxide (Page 3, 1st paragraph of Kim) as in instant Claims 1 and 12. Kim discloses wherein the solvent comprises phosphate-buffered saline (PBS) (Page 2, Means for Solving the Problem, 3rd Paragraph) as in instant Claim 15.
Kim does not specify the specific amount of bile salt that must be present in its cryopreservation preparation. 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 concentrations are critical. Absent such evidence, it would have been obvious to an artisan of ordinary skill at the time of effectively filing Kim to try a finite number of possible concentrations of bile salts to predictably arrive at the claimed concentration of bile salts in cryopreservation medium through routine optimization. An artisan would have a reasonable expectation of success in optimizing the concentration because determining the appropriate concentration of bile salts was long established in the art as in instant Claims 5 and 12.
It would have been obvious for an artisan of ordinary skill in the art to have optimized the concentration of bile salts disclosed in Kim in such a cryopreservation process. Such optimization and experimentation could have been easily determined by using different concentrations of bile salts and determining which concentrations produced the best effects. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary, that the skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in cryopreservation of cells. Therefore, the level of ordinary skill in this art is high.
Claims 1,3-10,12,14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (KR102116954) in view of Jennings (US 20100168011)
Kim applies as above to teach claims 1,3-5,8-10,12,15. Kim teaches that multiple bile salts can be used as surfactants/detergents in cryopreservation/lyophilization to include sodium cholate and sodium deoxycholate. Kim does not teach that sodium lithocholate is used specifically as a surfactant/detergent. However, Jennings teaches that sodium lithocholate can be used successfully as a detergent/surfactant. It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the detergent/surfactant in Jennings (sodium lithocholate) with the cryopreservation solution of Kim. An artisan would have been motivated to have used sodium lithocholate as the detergent/surfactant in place of sodium cholate or sodium deoxycholate because it can also function as a detergent/surfactant used in a freezing preparation (Paragraph 271 of Jennings). Paragraph 271 of Jennings teaches that sodium lithocholate can successfully be used in a freezing process; therefore, there would have been a high expectation for success that sodium lithocholate can be used in the cryopreservation/freezing process of Kim as in instant Claims 1,6,12, and 14.
Jennings does not expressly teach the claimed concentration of sodium lithocholate recited in the instant set of claims. 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 concentrations of sodium lithocholate are critical. Absent such evidence, it would have been obvious to an artisan of ordinary skill at the time of effectively filing Kim/Jennings to try a finite number of possible concentrations of bile salts/sodium lithocholate to predictably arrive at the claimed concentration through routine optimization. An artisan would have a reasonable expectation of success in optimizing the concentration because determining the appropriate concentration of bile salt/sodium lithocholate was long established in the art as in instant Claims 7 and 12.
Dependent Claims taught by Jennings
Jennings teaches wherein the bile salt is dissolved in a solvent to form the solution and the solution is applied to the cryopreserved substrate (Paragraphs 11-16,22-24 of Jennings) as in instant Claim 3. Jennings teaches wherein the bile salt is applied to the biological substrate before freezing (Abstract and Paragraphs 7-8 of Jennings) as in instant Claim 8. Jennings teaches wherein the bile salt is applied to the biological substrate during the freezing process (Abstract and Paragraphs 22-24 of Jennings) as in instant Claim 9. Jennings discloses wherein the bile salt is applied to the biological substrate by immersing the biological substrate in the solution containing the bile salt (Paragraph 41 of Jennings) as in instant Claim 10.
It would have been obvious for an artisan of ordinary skill in the art to have optimized the concentration of bile salts mentioned in Kim/Jennings in such a cryopreservation process. Such optimization and experimentation could have easily been accomplished by using different concentrations of bile salts and determining which concentration produced the best results. Furthermore, Kim teaches that surfactants/detergents that can be used with its cryopreservation process (a freezing process) include sodium cholate and sodium deoxycholate. Jennings further teaches that sodium cholate, sodium deoxycholate, and sodium lithocholate (NaLC) can be used as surfactants/detergents in freezing solutions/processes (Paragraph 271 of Jennings). Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary, that the skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in cryopreservation of cells. Therefore, the level of ordinary skill in this art is high.
Claims 1,3-5,8-12,15 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (KR102116954) in view of Yanhong Xu (CN 109644989)
Kim applies as above to teach claims 1,3-5,8-10,12,15. Kim does not teach that the cryopreservation solution can be added to the biological substrate/cells by dripping the cryopreservation solution on the biological substrate. However, Page 3, Example 2 of Xu states that cryopreservation solution can be added to a biological specimen by dripping it on a biological sample (Page 3, Example 2). It would have been obvious to an artisan of ordinary skill at the time of effective filling to have used the dripping method of Xu. An artisan would have been motivated to have used Xu’s drip application method taught in Example 2 since it can be used to apply cryopreservation solution to biological material (Xu, Page 3 Example 2). There would have been a high expectation for success because Xu teaches that such a method can be used to effectively add cryopreservation solution to a biological specimen (Page 3, Example 2 of Xu) as in instant Claim 11.
Kim teaches immersing the biological substrate/cells in a cryopreservation solution. Kim does not administer the cryopreservation solution to the cells using a drip method. However, it would have been obvious to have used the dripping administration method of Xu since it is yet another way that the cryopreservation solution can be successfully applied to a biological substrate/cells. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary, that the skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in cryopreservation of cells. Therefore, the level of ordinary skill in this art is high.
Conclusion
All claims stand 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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