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 1-3,5-10,12-17,19-20, and 22 are under examination.
Response to Applicants Arguments/Amendments
Because indefinite claims have been canceled, the 112(b) rejection is withdrawn. The arguments for each rejection are directly placed under that rejection. An additional written description rejection has been added based on the new claim amendments.
Claim Rejections - 35 USC § 112
Claims 1-3,5-10,12-17,19-20, and 22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for preserving living large volume cellular material and/or cartilage comprising exposing the living large volume cellular material/cartilage to a solution of high concentration cryoprotectant formulation with iron metal nanoparticles (Fe mNPs); obtaining a cryopreserved cellular material/cartilage from the exposed cellular material/cartilage by subjecting the exposed cellular material/cartilage to a preservation protocol in which damage to the exposed cellular material/cartilage due to freezing does not occur; and nanowarming the cryopreserved cellular material/cartilage such that metabolic activity of the nanowarmed tissue is recovered to in a range of 70% to 100% of control values within two days of being rewarmed, the control values corresponding to metabolic activity of fresh cellular material/cartilage, which was not cryopreserved, in a growth media, wherein the total concentration of Fe mNPs in the high concentration cryoprotectant formation is in the range of from 2 mg/ml to 3 mg/ml, and wherein the high concentration cryoprotectant formulation comprises 4.65 mol/L dimethyl sulfoxide, 4.65 mol/L formamide, and 3.31 mol/L propylene glycol in 1xEuroCollins solution does not reasonably provide enablement for a method for preserving living large volume cellular material and/or cartilage tissue comprising exposing the living large volume cellular material/cartilage to a solution of high concentration cryoprotectant formulation; obtaining a cryopreserved cellular material/cartilage from the exposed cellular material by subjecting the exposed cellular material to a preservation protocol in which damage to the exposed cellular material/cartilage due to freezing does not occur; and nanowarming the cryopreserved cellular material/cartilage such that metabolic activity of the nanowarmed tissue is recovered to in a range of 70% to 100% of control values within two days of being rewarmed, the control values corresponding to metabolic activity of fresh cellular material/cartilage, which was not cryopreserved, in a growth media, wherein the total concentration of Fe mNPs in the high concentration cryoprotectant formation is in the range of from 2 mg/ml to 3 mg/ml, and wherein a cryoprotectant agent concentration in the high concentration cryoprotectant formulation is in a range of 75% to 83%, and wherein the high concentration cryoprotectant agent comprises 3.88-4.65 mol/L dimethyl sulfoxide, 3.88-4.65 mol/L formamide, and 2.75-3.31 mol/L propylene glycol in 1x Euro Collins Solution. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Nature of the Invention:
Applicants last submitted set of claims encompassed a method for preserving large volume cellular material (Claim 1)/cartilage tissue (Claim 16) by exposing such material to a solution containing a high concentration of cryoprotectant formation. The preservation method in independent claims 1 and 16 recite exposing the living large volume cellular material/cartilage to a solution of high concentration cryoprotectant formulation containing Fe mNPs; obtaining a cryopreserved cellular material/cartilage from the exposed cellular material/cartilage by subjecting the exposed cellular material/cartilage to a preservation protocol in which damage to the exposed cellular material/cartilage due to freezing does not occur; and nanowarming the cryopreserved cellular material/cartilage such that the metabolic activity of the nanowarmed tissue is recovered to in a range of 70% to 100% of the control values within two days of being rewarmed, the control values corresponding to metabolic activity of fresh cellular material/cartilage, which was not cryopreserved, in a growth media, wherein a total concentration of Fe mNPs in the high concentration cryoprotectant formulation is in the range of from 2 mg/mL to 3 mg/mL, and wherein a cryoprotectant agent concentration in the high concentration cryoprotectant formulation is in the range of 75% to 83%. On June 17, 2026, applicants offered amended claims that required the high concentration cryoprotectant formulation to comprise 3.88-4.65 mol/L dimethyl sulfoxide, 3.88-4.65 mol/L formamide, and 2.75-3.31 mol/L propylene glycol in 1xEuroCollins solution in the independent claims.
Breadth of the Claims:
The claims require that a cryoprotectant formulation is used in the process. The claims have been amended to state that the range for cryoprotectant formulation includes the following: 3.88-4.65 mol/L dimethyl sulfoxide, 3.88-4.65 mol/L formamide, and 2.75-3.31 mol/L propylene glycol in 1 x Euro Collins solution.
Applicants Specification/Guidance/Working Examples:
Figure 1 of applicants’ specification only shows that a metabolic activity for recovered cells of 70-100% after a freezing/thawing process is possible when VS83 is used. VS83 is a tradename. In the specification, VS83 has the following components: 4.65 mol/L dimethyl sulfoxide, 4.65 mol/L formamide, and 3.31 mol/L propylene glycol in 1x Euro Collins solution in combination with about 2mg/mL of Fe mNPs. Paragraph 61 of the specification states that this VS83 formulation has a molarity of 12.6 M. No other concentration is shown to produce recovered cells with a metabolic activity level of 70-100% after the freeze/thaw process.
Figure 1 shows that the following cryopreservation formulations VS55 and VS70 did not result in the high metabolic activity level recited in the claims. Figure 7 and Paragraph 131 teach that cryoprotectant formulations VS55 and DP7 (DMSO AND 1,2-propanediol with disaccharides) with cryoprotective agents (sucrose and/or trehalose) were unable to obtain a high metabolic level (70-100%) recited in the claim language. VS55 has the same components as VS83 but at a lower concentration, and VS55 cannot generate the metabolic activity level after thawing recited in the instant claims. VS70 has levels of cryoprotectants between VS55 and VS83 (Figure 1); however, it does not successfully produce cells that have a high metabolic activity (70-100%) after thawing. Figure 1 shows that the VS83 formulation at its stated concentrations with the iron nanoparticles can provide cells with a high metabolic activity (70-100%) after thawing. The specification does not even mention VS75 wherein the high concentration of cryoprotectant agent comprises 3.88 mol/L dimethyl sulfoxide, 3.88 mol/L formamide, and 2.75 mol/L propylene glycol in 1x Euro Collins solution.
Conclusion: Because applicant has only demonstrated that a high metabolic activity (70-100%) after thawing is possible with just the VS83 solution and about 2 mg/mL Fe mNPs, applicant should only be entitled to that embodiment.
Response to Applicants’ Arguments
Applicants argue that Figure 1 VS70 (70% cryopreservation agent) illustrates that at least 70% of the metabolic activity is restored after thawing. Figure 1 might show that VS70 can reach a preservation level of 70% but it does not appear to reach upwards to 80%,90%, or 100% preservation as recited in the instant set of claims. Furthermore, the specification does not even mention the range of VS75 (75%) to VS83 (83%) which is now claimed or what the concentration range of each cryoprotectant agent is at VS75. Not only is this an enablement issue but it is now a written description issue.
Written Description Rejection:
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3,5-10,12-17,19-20, and 22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Instant claim 1 now includes that living large volume of cellular material can be successfully preserved using a total cryoprotectant agent concentration in the high concentration cryoprotectant formulation in a range of 75% to 83%, and wherein the high concentration cryoprotectant agent comprises 3.88-4.65 mol/L dimethyl sulfoxide, 3.88-4.65 mol/L formamide, and 2.75-3.31 mol/L propylene glycol in 1xEuro Collins solution.” The same claim further recites that the range of cryoprotectant agents allow for “nanowarming the cryopreserved cellular material such that metabolic activity of the nanowarmed tissue is recovered to a range of 70% to 100% of the control value within two days of being nanowarmed.”
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the filed of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F. 3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F. 3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. “Vas-Cath, Inc. v. Mahurkar, 935 F. 2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04
A described in MPEP § 2163, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice...reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus”...See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."
The claims now recite that a cryoprotectant in the range of 75% to 83% (3.88-4.65 mol/L dimethyl sulfoxide, 3.88-4.65 mol/L formamide, and 2.75-3.31 mol/L propylene glycol in 1xEuro Collins solution) results in the nanowarmed tissue being recovered to a range of 70% to 100% of the control value within two days of being rewarmed. This is problematic because the specification does not teach a cryoprotectant range of 75% to 83%. Instead, the specification discloses results for VS55 (55%), VS70 (70%), and VS83 (83%) only (Figure 1A); no 75% to 83% range is provided. Only Figure 1 shows that the VS83 formulation at its stated concentration with the iron nanoparticles can provide cells with a high metabolic activity (70-100%) after thawing.
In Conclusion: Only one species (a cryoprotectant in the range of 83%---4.65 mol/L dimethyl sulfoxide, 4.65 mol/L formamide, and 3.31 mol/L propylene glycol in 1x Euro Collins Solution) is present in the specification. This is only one point in the claimed range; therefore, applicants are only entitled to that species and not the entire range now claimed of 75% to 83%.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGFs were found to be unpatentable due to lack of written description for that broad class. The specification only provided the bovine sequence.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3,5-10,12-17,19-20,22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of Application 19/310,608. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and those of Application 19/310,608 have the same limitations with the exception that the concentrations of the dimethyl sulfoxide, formamide, and 1,2-propanediol are lower in the claims of 19,310,608. It would have been expected that a person of ordinary skill would have modified the amount of cryoprotectant formula to best preserve the living large volume of cellular material/cartilage. Instant claims 1 and 4 correspond to claim 1 of 19/310,608. Instant claim 2 corresponds to claim 2 of 19,310,608. Instant claim 3 corresponds to claim 3 of 19/310,608. Instant claim 5 corresponds to claim 4 of 19,310,608. Instant claim 6 corresponds to claim 5 of 19,310,608. Instant claim 7 corresponds to claim 6 of Application 19,310,608. Instant claim 8 corresponds to claim 7 of Application 19,310,608. Instant claim 9 corresponds to claim 8 of Application 19,310,608. Instant claim 10 corresponds to claim 9 of Application 19,310,608. Instant claim 12 corresponds to claim 10 of Application 19,310,608. Instant claim 13 corresponds to claim 11 of Application 19,310,608. Instant claim 14 corresponds to claim 12 of Application 19,310,608. Instant claim 15 corresponds to claim 13 of Application 19,310,608. Instant claim 16 corresponds to claims 14 and 18 of Application 19,310,608. Instant claim 17 corresponds to claim 15 of Application 19,310,608. Instant claim 19 corresponds to claim 16 of Application 19,310,608. Instant claim 20 corresponds to claim 17 of Application 19,310,608. Instant claim 22 corresponds to claim 18 of Application 19,310,608.
Response to Applicants’ Arguments:
This nonstatutory double patenting rejection is maintained because a terminal disclaimer has not been submitted timely.
Conclusion
All claims stand rejected.
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are 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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