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 .
Election/Restrictions
Applicant’s election with traverse of Group I (Claims 1-3 and 13-16; drawn to a method for treating a tissue or organ in a subject in need thereof comprising administering a therapeutically effective amount of encapsulated cells to the tissue or organ) in the reply filed on December 19, 2024, is acknowledged.
Claims 4-12 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (Groups II and III), there being no allowable generic or linking claim.
DETAILED ACTION
The amended claims filed on July 22, 2025, have been acknowledged. Claims 2-3 and 16 were cancelled. Claims 1 was amended. Claims 18-19 are new. In light of the Applicant’s elected invention, claims 4-12 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 13-15, and 18-19 are pending and examined on the merits.
Priority
The applicant claims domestic priority from U.S. provisional application No. 62/873,365, filed on July 12, 2019. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1, 13-15, and 18-19 receive domestic benefit from U.S. provisional application No. 62/873,365, filed on July 12, 2019.
Withdrawn Objection to Specification
The prior objection to the specification has been withdrawn in light of Applicant’s amendments to the specification to identify the SEQ ID NOs found in Figures 8 and 12.
Withdrawn Objection to Drawings
The prior objection to the drawings has been withdrawn in light of Applicant’s amendments to the specification to identify the SEQ ID NOs found in Figures 8 and 12 in the description of the drawings.
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claims 1-3 and 13-15 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by United States Patent Application No. 20150320833 (Stice) is withdrawn in light of Applicant’s amendments to claim 1 to require transfection of BMP7 and treatment of specific conditions.
The prior rejection of claims 1-2, 13, and 15-16 under 35 U.S.C. 102(a)(1) as being anticipated by United States Patent Application No. 20180037868 (Gunther) is withdrawn in light of Applicant’s amendments to claim 1 to require transfection of BMP7 and treatment of specific conditions.
Claim Rejections - 35 USC § 103
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.
Claims 1, 13, 15, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Experimental and Molecular Pathology 102: 70-77. 2017), Ma et al. (Am J Physiol Lung Cell Mol Physiol 312: 741-747. 2017), and Liu et al. (Int J Radiation Oncol Biol Phys 101: 945-956. 2018).
Regarding claim 1, Li teaches a method of treating induced pulmonary fibrosis in rats comprising overexpressing BMP7 in mesenchymal stem cells through lentivirus transduction and administering the cells to the rats via tail vein injection. BMP7 transduced mesenchymal stem cells significantly reduced the pulmonary fibrosis levels, indicating there is an anti-fibrotic effect from mesenchymal stem cells overexpressing BMP7. Li teaches that collagen levels were reduced when administering the BMP7 MSCs (abstract, Figures 3-6, and page 72, column 1, paragraph 3-page 76, column 2, paragraph 4).
Li does not teach wherein the BMP7 overexpressing mesenchymal stem cells are encapsulated.
However, Ma teaches a method of treating induced pulmonary fibrosis in mice comprising overexpressing Lefty A in HEK293 cells, encapsulating the HEK293 cells, and subcutaneously implanting them. Ma teaches that their engineered HEK cells attenuated pulmonary fibrosis by reducing collagen levels (abstract and lines 260-307). Ma teaches that alginate encapsulation can protect cells from host reactivity in immunocompetent mice and that encapsulated MSCs have previously been used to treat lung fibrosis (lines 317-332).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating pulmonary fibrosis of Li by encapsulating the BMP7 MSCs in alginate, as identified by Ma, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to modify with a reasonable expectation of success because Ma teaches that alginate encapsulation can protect cells from host reactivity in immunocompetent mice and that encapsulated MSCs have previously been used to treat lung fibrosis. Furthermore, Ma teaches that their genetically modified, encapsulated cells also decreased collagen levels like the BMP7 MSCs of Li. Therefore, it would have been obvious that the BMP7 MSCs of Li could be encapsulated while still being able to have the therapeutic effect of reducing collagen levels and reducing the severity of pulmonary fibrosis. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
The combined teachings of Li and Ma do not teach wherein the cells are transfected. Instead, they use transduction with a lentivirus.
However, Liu teaches a method of treating induced pulmonary fibrosis comprising administering mesenchymal stem cells transfected with an adenovirus encoding decorin to mice via intravenous administration. This was shown to reduce pulmonary fibrosis levels and collagen levels in the mice up to 28 days after MSC administration (abstract and page 946, column 1, paragraph 1-page 954, column 1, paragraph 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the method of overexpressing BMP7 from lentiviral transduction and integration to adenovirus transfection, as identified by Liu, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Liu teaches that mesenchymal stem cells genetically modified through transfection were still able to elicit a therapeutic response lessening pulmonary fibrosis and collagen levels for at least 28 days. Furthermore, lentiviral integration is known to increase the risk of insertional mutagenesis and malignant cell transformation as part of the random integration of the lentivirus. On the contrary, adenoviruses are episomal and do not integrate into the genome, removing this as a possible risk factor for treatment. Therefore, it would have been obvious to use an adenovirus for BMP7 overexpression as there are reduced risk of insertional mutagenesis and malignant cell transformation and Liu teaches that the adenovirus can still maintain therapeutic effects for at least 28 days. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claim 13, Li teaches they treated rats and Ma and Liu teach they treated mice, all of which are mammals.
Regarding claim 15, Li, Ma, and Liu consider their animal model studies as being important for generating treatments for humans (Li: page 70, column 1, paragraph 1-page 71, column 1, paragraph 1; Ma: abstract; Liu: page 946, column 1, paragraph 1-3). Therefore, it would have been obvious that a similar treatment could be used in humans. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claim 18, Li and Liu do not teach using human stellate cells nor human embryonic kidney cells.
However, Ma, as stated supra, teaches that they transduced HEK293 cells to treat induced pulmonary fibrosis and were able to achieve reductions in pulmonary fibrosis severity and collagen levels (abstract and lines 260-307), which is the same as was found with the genetically modified MSCs of Li and Liu. Therefore, it would have been obvious that HEK293 cells could also be used to overexpress BMP7 to treat pulmonary fibrosis. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Claims 1 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Experimental and Molecular Pathology 102: 70-77. 2017), Ma et al. (Am J Physiol Lung Cell Mol Physiol 312: 741-747. 2017), and Liu et al. (Int J Radiation Oncol Biol Phys 101: 945-956. 2018), as applied to claim 1 above, and further in view of United States Patent Application No. 20150320833 (Stice).
The teachings of Li, Ma, and Liu are as discussed above.
The teachings of Li, Ma, and Liu do not teach wherein the subject is a non-human primate.
Stice teaches a method of treating a bone or cartilage disorder comprising administering a composition of mesenchymal stem cells that have been transfected with a plasmid comprising a sequence encoding BMP-7 and encapsulated in a biomaterial to a patient (claims 1-3, 7-10 and 22 and 23 and paragraphs 0018-0028). Stice teaches that their method can be used to treat mice, humans, non-human primates, and other veterinary or domesticated animal (paragraph 0056 and examples 4 and 7).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that one could use this method to also treat humans and non-human primates, as identified by Stice, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to treat humans and non-human primates with a reasonable expectation of success because Stice teaches that mesenchymal stem cells overexpressing BMP7 and encapsulated can treat laboratory animals such as mice, humans, and non-human primates. Furthermore, mice, rats, and non-human primates are known to be animal models for developing treatments for human clinical use. Therefore, it would have been well understood that the method of the combined teachings of Li, Ma, and Liu could be used to treat humans and non-human primates. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Claims 1 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Experimental and Molecular Pathology 102: 70-77. 2017), Ma et al. (Am J Physiol Lung Cell Mol Physiol 312: 741-747. 2017), and Liu et al. (Int J Radiation Oncol Biol Phys 101: 945-956. 2018), as applied to claim 1 above, and further in view of Xu et al. (Stem Cell Translational Medicine 7: 721-730. 2018).
The teachings of Li, Ma, and Liu are as discussed above.
The teachings of Li, Ma, and Liu do not teach wherein the transfected cells are administered a selection agent and subject to clonal selection prior to encapsulation.
However, Xu teaches that puromycin selection gene markers can be included in viral vectors to allow for selection of mesenchymal stem cells that are transfected with their gene of interest. Puromycin-resistant cells were then collected and later used for transplantation into mice tail vein injection (page 722, column 1, paragraph 4-column 2, paragraph 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of overexpressing BMP7 from transfection by including a puromycin selection marker and puromycin selection step, as identified by Xu, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to modify with a reasonable expectation of success because puromycin selection is commonly used in the field to identify and select for cells that have been successfully modified with the gene of interest. Furthermore, Xu successfully reduces to practice that puromycin selection markers can be used to select for genetically modified MSCs. Therefore, it would have been obvious to one of ordinary skill in the art that the vector could include a puromycin selection marker and the MSCs could undergo selection for cells that were successfully transfected. This would obviously occur prior to encapsulation to ensure only successfully transfected cells are encapsulated and administered to the subject for treatment. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Conclusion
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 KEENAN A BATES whose telephone number is (571)270-0727. The examiner can normally be reached M-F 7:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KEENAN A BATES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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