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 .
Applicant’s amendment and response filed on 9/29/2025 has been received and entered into the case.
Claims 1-33, 35 have been canceled, claims 44-46 are newly added, claims 39-43 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 34, 36-38 and 44-46 have been considered on the merits. All arguments have been considered.
The claim rejection under 35 USC 112(b) has been withdrawn due to the instant amendment.
The claim rejection under 35 USC 103 has been withdrawn due to the instant amendment.
The double patenting rejections have been withdrawn due to the instant amendment.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 16/983,190, 14/810,003, and 62/194,574 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The instant claims disclose “cadaverous vertebral bodies” in claim 44 as a source of the exosome isolated by the claimed method. None of the above listed prior applications disclose the subject matter.
Furthermore, claim 44 requires that the freeze-dried or frozen cryoprotected exosomes have enhanced osteoinductive properties relative to control exosomes. None of the listed prior applications disclose the subject matter including 16/710,472, and 62/794,912. It is noted that 16/710,472, and 62/794,912 as well as the instant specification disclose “the uptake assay revealed that more exosomes, cryoprotected and lyophilized, were taken up by hMSCs compared to DPBS exosomes, pointing to a potential mechanism for its enhanced osteoinductive capabilities”. This disclosure supports the cryoprotected and lyophilized exosome (i.e. freeze-dried exosomes) whereas the instant claims disclose either frozen or freeze-dried.
Thus, based on the above discussion, the earliest priority date of the instant application is determined as 11/01/2022.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Claim 44 requires “the freeze-dried or frozen cryoprotected exosomes” having enhanced osteoinductive properties. However, the instant specification discloses the uptake assay revealed that more exosomes, cryoprotected and lyophilized, were taken up by hMSCs compared to DPBS exosomes, pointing to a potential mechanism for its enhanced osteoinductive capabilities (para. [0054]). This statement does not support the limitation of claim 1 discussed above. The fact given by this disclosure is that the freeze-dried exosomes are taken up by hMSCs more than the control. It does not provide support for cryopreserved (frozen) but not dried exosomes.
Claims 45-46 disclose that the shelf-life of the exosome being at least 1 year or 2 year. The instant specification discloses that the expected shelf-life for both frozen liquid and freeze-dried configurations is two years from the final packaging date (para. [0035]). Thus, the instant specification fails to provide proper antecedent basis for the claimed subject matter.
Claim Rejections - 35 USC § 112 (New 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 34, 36-38 and 44-46 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. This is a new matter rejection.
The amended claims disclose:
Freeze-dried or frozen cryoprotected exosomes would have enhanced osteoinductive properties compared to the control (claim 44), and
The shelf-life of either freeze-dried or frozen cryoprotected exosomes have the shelf-life at least 1 year or 2 years (claims 45-46).
The instant specification fails to provide support to the limitation of claim 44 directed to the osteoinductive properties of the exosome as it only provides support for freeze-dried exosomes. The specification discloses “the uptake assay revealed that more exosomes, cryoprotected and lyophilized, were taken up by hMSCs compared to DPBS exosomes, pointing to a potential mechanism for its enhanced osteoinductive capabilities” (para. [0054]).
Claims 45-46 disclose that the shelf-life of the exosome being at least 1 year or 2 year. The instant specification discloses that the expected shelf-life for both frozen liquid and freeze-dried configurations is two years from the final packaging date (para. [0035]). It is noted that the specification also discloses “[t]he current expiration date of both the frozen and freeze-dried configurations of the Spine Derived Exosome Product is 2 years from the date of freezing. These dates are likely to be much longer, and in the case of the freeze-dried product, may be stored indefinitely in their vacuum sealed containers” (para. [0046]). While paragraph [0046] is considered to support “at least 1 year” or “at least 2 years”, however, it requires the storage in a vacuum sealed container. As the claims do not require any vacuum sealed containers, the limitation of the claims is the broader scope than the support provided by the specification.
Therefore, the instant amendment introduces new matter to the instant application.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 34 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 34 discloses “the incubation”. There is no antecedent basis for the term as claim 44 does not disclose any incubation.
Claim Rejections - 35 USC § 103 (New Rejection)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 34, 38 and 44-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weston et al. (US 2016/0256490)
Regarding claim 44, Weston et al. teach a method of isolating exosomes from a biological composition having a mixture of mechanically selected allogeneic biologic material derived from bone marrow, and the mixture has non-whole cellular components including exosomes (para. 7). Weston et al. teach that the bone marrow is from cadaverous bone including a vertebral body taken from a spine of a cadaver donor (para. 25 and 36).
Regarding the steps (a) and (b), Weston et al. teach the step of separating the cellular components of bone marrow from the cadaverous bone using the processing medium washing cycle, and collect decanted fluid after sieving the processing media using 500 mm and 180 mm sieve (para. 39-41).
Weston et al. further teach the collected decanted fluid is then centrifuged to separate the mixture including whole cells from the soft marrow tissue and the remaining bone is discarded (para. 41), and the cells are separated from the non-whole cell components by density centrifugation (para. 42). This teaching is considered to meet the step (c).
Weston et al. teach the supernatant after the removal of the cell fraction is further filtered through 0.45 and 0.2 mm filters, and exosomes are further collected and separated within the suspension in centrifugation steps and density gradient-based isolation (para. 44-45), and this teach meets the step (d).
Regarding the step (e), While Weston et al. teach the step of mixing the non-cellular component with a polyampholyte cryoprotectant and freezing or freeze-drying the mixture (para. 9, 12; p.4, claim 9), however, Weston et al. do not particularly disclose that the isolated exosomes are cryopreserved. However, it would have been obvious to a person skilled in the art to cryopreserve or freeze dry the isolated exosomes for a storage purpose. A person of ordinary skilled in the art would have been motivated to do so because Weston et al. teach that the biological composition comprising non-whole cellular component including exosomes are cryopreserved or freeze dried. Thus, it is reasonable to store the isolated exosomes from the non-whole cellular component taught by Weston et al. in a mixture with a cryoprotectant and cryopreserve or freeze dry the exosomes with a reasonable expectation of success.
Regarding the wherein clause of step (f) directed to the property of the exosomes that have been cryopreserved or freeze-dried, this limitation does not require any active step to be performed for the claimed method and thus, it does not provide any patentable weight in determining patentability of the claimed method of preparing the exosome product. As the teachings of Weston et al. meet the claimed method steps, the resulted product of Weston et al. is expected to have the identical property as claimed.
Regarding the limitation of claims 45-46 directed to the shelf-life of the freeze-dried or frozen cryoprotected exosomes being at least 1 or 2 year, Weston et al. do not teach the limitation. The wherein clauses of these claims do not require any active step to be performed for the claimed method and thus, the wherein clause does not provide any weight in determining the patentability of the claimed method. Rather the wherein clause provides the results of the freeze-drying or freezing step of the exosomes, and thus, the limitation directed to the shelf-life is inherent to the cryopreservation or freeze-drying of the cryoprotected exosomes. As Weston et al. teach the use of polyampholyte cryoprotectant for cryopreservation, it is expected that the exosomes cryoprotected and cryopreserved or freeze-dried would have the identical properties as claimed.
Regarding claim 34 directed to the incubation being for 18-24 hrs., the newly added claim 44 does not disclose any step of incubating. However, if the step (a) of claim 44 is considered as an incubating step,
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weston et al. as applied to claim 44 above, and further in view of Matsumura et al. (2010, Cell Transplantation; IDS ref.).
Regarding claim 36 directed to the cryoprotectant being COOH-PLL, Weston et al. do not teach the limitation.
Matsumura et al. teach that COOH-PLL is a polyampholyte cryoprotectant (p.1, Introduction).
It would have been obvious to a person skilled in the art to use COOH-PLL taught by Matsumura et al. as the polyampholyte cryoprotectant used in the method of Weston et al. as COOH-PLL is known as a polyampholyte cryoprotectant according to Matsumura et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weston et al. (supra) as applied to claim 44 above, in view of Kommawar et al. (2014, RJPBCS; of record)
Regarding claim 37 directed to the step of storing the freeze-dried composition of exosomes in a vacuum-sealed container at ambient temperature, the cited references do not particularly teach the limitation. However, freeze-drying technique or lyophilization is extremely well known in the art for the storage of biological materials according to Kommawar et al. Kommawar et al. teach that lyophilization is a process which extracts the water from foods and other products remain stable and easier to store at room temperature (ambient temperature) and lyophilization maintains food/biochemical and chemical reagent quality (Abstract) and it is ideal for processing valuable or sensitive biological materials (p.5, Advantages).
Thus, it would have been obvious to a person skilled in the art to store the freeze-dried exosome prepared by the method of Weston et al. using the vacuum sealed container taught by Kommawar et al. As it is well known in the art that the lyophilized biomaterials would be stored vacuum sealed containers that prevent moist entering the container and maintain the dryness as taught by Kommawar et al. Thus, it would have been obvious to a person skilled in the art to use a vacuum sealed container for the lyophilized exosome of Weston et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weston et al. as applied to claim 44 above, and further in view of Lee et al. (2016, Biotechnology and Bioprocess Engineering)
Regarding claim 38 directed to the storage temperature of frozen cryoprotected exosomes being about -65°C, Weston et al. teach the range of cryopreservation temperature being 0 to -200°C (para. 10). Furthermore, Lee et al. teach that the most used condition of exosome preservation is -70°C (p.303, 1st col.). Thus, it would have been obvious to a person skilled in the art to use the temperature -70°C for the storage of the exosomes of Weston et al. The temperature of -70°C would meet the limitation of “about -65°C”.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Double Patenting (New Rejection)
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 34, 36-38 and 44-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9,687,511 in view of Kommawar et al. (supra), Matsumura et al. (supra) and Lee et al. (supra)
Although the claims at issue are not identical, they are not patentably distinct from each other because the claim of the ‘511 patent disclose a method of making a biological composition from bone marrow derived from cadaverous bone comprising processing the bone marrow, separating and collecting non-cellular fractions or non-cellular components excluding the whole cells, concentrating by using centrifugation and filtration, and quantifying the concentration, and suspending the mixture of the non-cellular fractions or non-cellular components in a polyampholyte cryoprotectant, and then freezing the mixture. The scope of cadaverous bone of the ’511 patent encompass and exemplified as vertebral bodies. The scope of non-cellular fractions or non-cellular components of the ‘511 patent would encompass exosomes of the instant claims.
The claim of the ‘511 patent does not teach the step of isolating exosomes. However, it is known in the art that exosomes are isolated from MSCs and bone marrow is a source of mesenchymal stem cells. Thus, it would have been obvious to a person skilled in the art to isolate exosomes from the non-cellular fraction or components of the ‘511 patent with a reasonable expectation of success.
While the claim of the ‘511 patent does not particularly disclose the step of freeze-drying the exosomes or COOH-PLL, however, it is known in the art that the polyampholyte cryoprotectant includes COOH-PLL according to Matsumura et al., and freeze-drying of biological composition is extremely well known in the art as an alternative means for storage to freezing according to Kommawar et al.
Regarding the frozen exosomes being stored at about -65°C, while the claim of the ‘511 patent does not particularly disclose the limitation, however, it is known in the art that -70°C is commonly used temperature for exosome storage according to Lee et al.
Regarding the limitation of claims 45-46 directed to the shelf-life of the freeze-dried or frozen cryoprotected exosomes being at least 1 or 2 year, the claim of the ‘511 patent do not teach the limitation. However, the wherein clause provides the results of the freeze-drying or freezing step of the exosomes, and thus, the limitation directed to the shelf-life is inherent to the cryopreservation or freeze-drying of the cryoprotected exosomes taught by the combined teaching of the claim of the ‘511 patent combined with the teachings of the cited references.
Thus, the claim of the ‘511 patent in view of the cited references above would render the claims of the instant application obvious.
Claims 34, 36-38 and 44-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,760,058 in view of Weston et al., Kommawar et al., Matsumura et al. and Lee et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claim of the ‘058 patent disclose a method of making a biological composition from bone marrow derived from cadaver donors comprising processing the bone marrow, separating and collecting non-cellular fractions or non-cellular components excluding the whole cells, concentrating by using centrifugation and filtration, and quantifying the concentration, and suspending the mixture of the non-cellular fractions or non-cellular components in a polyampholyte cryoprotectant, and then freezing the mixture. The scope of cadaverous bone of the ’058 patent encompass and exemplified as vertebral bodies. The scope of non-cellular fractions or non-cellular components of the ‘058 patent would encompass exosomes of the instant claims.
The claim of the ‘058 patent does not teach the step of isolating exosomes. However, it is known in the art that exosomes are isolated from MSCs and bone marrow is a source of mesenchymal stem cells. Thus, it would have been obvious to a person skilled in the art to isolate exosomes from the non-cellular fraction or components of the ‘058 patent with a reasonable expectation of success.
While the claim of the ‘058 patent does not particularly disclose the step of freeze-drying the exosomes or COOH-PLL, however, it is known in the art that the polyampholyte cryoprotectant includes COOH-PLL according to Matsumura et al., and freeze-drying of biological composition is extremely well known in the art as an alternative means for storage to freezing according to Kommawar et al.
Regarding the frozen exosomes being stored at about -65°C, while the claim of the ‘058 patent does not particularly disclose the limitation, however, it is known in the art that -70°C is commonly used temperature for exosome storage according to Lee et al.
Regarding the limitation of claims 45-46 directed to the shelf-life of the freeze-dried or frozen cryoprotected exosomes being at least 1 or 2 year, the claim of the ‘058 patent do not teach the limitation. However, the wherein clause provides the results of the freeze-drying or freezing step of the exosomes, and thus, the limitation directed to the shelf-life is inherent to the cryopreservation or freeze-drying of the cryoprotected exosomes taught by the combined teaching of the claim of the ‘058 patent combined with the teachings of the cited references.
Thus, the claim of the ‘058 patent in view of the cited references above would render the claims of the instant application obvious.
Response to Arguments
Applicant’s arguments with respect to claim(s) 27-35 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.
Conclusion
No claims are allowed.
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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/TAEYOON KIM/Primary Examiner, Art Unit 1631