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 election without traverse of Group I, encompassing claims 1-2 and 9 directed to a process comprising inhibiting expression of TGF-beta R1 in the reply filed on 02/26/2025 is acknowledged.
Claims 3-8 and 10-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/26/2025.
Newly submitted claim 13 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claim 13 is drawn to a method for inducing transdifferentiation of somatic cells into mammary epithelial cells in vitro, utilizing gene interference. This method is patentably distinct from the method encompassing Group I of the elected invention. The methods of the elected invention and 13 are distinct methods for inducing transdifferentiation of somatic cells into mammary epithelial cells. The small molecules of the elected invention are not required for the induction of the cells in claim 13. The lentiviral recombinant plasmid and methods for gene interference of claim 13 are not required for the method of the elected invention.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 13 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. CN201911328267.2, filed on 07/27/2022.
Information Disclosure Statement
The IDS filed 07/27/2022 has been considered by the Examiner.
Status of Claims
Claim 1 is under examination.
Claims 3-8 and 10-13 are withdrawn.
Claims 2 and 9 have been canceled.
Claim Rejections - 35 USC § 112
Rejections to claims 1 and 2 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph have been withdrawn in view of the applicant’s amendments filed 06/12/2025.
Claim Rejections - 35 USC § 103
Claims 1, 2, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Piccolo (US 2018/0245038 Al) in view of Page (US 2003/0059939 Al) and Clarke (Tocris Scientific Review Series, 2018).
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Piccolo et al. (US 2018/0245038 Al) in view of Page et al. (US 2003/0059939 Al) and in further view of Clarke et al. (Tocris Scientific Review Series, 2018).
Regarding claim 1, Piccolo et al. teach a method for inducing transdifferentiation of somatic cells into mammary epithelial stem cells in vitro which reads on a method for inducing transdifferentiation into mammary epithelial cells in vitro (page 2, paragraph 0020). Piccolo et al. teach the starting cell can be any mammalian cell, including, but not limited to, terminally differentiated cells. Piccolo further teaches the cell is a human cell, mouse cell, or rat cell which reads on the somatic cells are derived from a human being, mouse, or rat. Piccolo et al. teach the cell may be a terminal differentiated cell, a committed progenitor or a partially differentiated cell or a cell with dual stem-differentiated traits which reads on somatic cell (page 2, paragraph 0020).
Piccolo et al. do not specifically teach ear fibroblasts or epidermal cells. Piccolo does not teach inhibiting the expression of TGF-beta R1 and sites thereof. Piccolo et al. do not specifically teach the small molecules compounds comprises valproic acid (VPA), Forskolin, Tranylcypromine, Arotinoid Acid (TTNPB), and one or more of SB431542, SB525334 and LDN193189.
Page et al. teach a method that can be used to effect trans-differentiation of any type of somatic cell into any other type of somatic cell (page 2, paragraph 0012). Page et al. teach a method for effecting trans-differentiation of a somatic cell comprising culturing a somatic cell in the presence of at least one agent selected from the group consisting of cytoskeletal inhibitors and inhibitors of acetylation, and inhibitors of methylation; culturing the cell in the presence of agents or conditions that induce differentiation to a cell type different than that of said somatic cell; and allowing the cell to trans-differentiate to said different cell type (pages 11-12, claim 1). Page et al. teach the methods which can be used to effect trans-differentiation of any type of any type of somatic cell into any other type of somatic cell (page 2, paragraph 0012). Page et al. teach that cells which can be used include fibroblasts and epidermal cells (page 2, paragraph 0012). Page further teaches the cells used with the methods of the invention may be mammal. Page et al. teach transdifferentiated cells could be human, bovine, buffalo, mouse, rat, rabbit sheep, goat, or pig (page 2, paragraph 0013).
Page does not specifically teach TGF-beta R1 inhibition or related sites.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Piccolo et al. for transdifferentiation of somatic cells into mammary stem cells with the teachings of Page et al. for transdifferentiation methods from one somatic cell to any other type. Page et al. provide motivation by teaching that cell type-designed culture conditions will yield cells resembling the expected cell type (page 7, paragraph 0093). Therefore, since the cells of Page et al. are primed for neuronal generation the addition of Piccolo’s methods for differentiation to a mammary lineage would be desired. One of skill in the art would have had a reasonable expectation of success at combining Piccolo et al. and Page et al. because both Piccolo et al. and Page et al. teach methods for transdifferentiation of somatic cells.
Clarke et al. teach somatic reprogramming and further teaches small molecules in the reprogramming of somatic cells. Clarke et al. teach small molecules targeting various ligands and targets in the TGF-b pathway, as inhibitors which have been used in the generation of both mouse and human iPS cells from somatic cells. Clarke et al. teach "RepSox" as a selective inhibitor of TGF-bR1 which plays a roles in the generation of iPS cells, which reads on inhibiting expression of TGFbeta R1(page 10, paragraph 4). Clarke et al. teach another target for small molecules in the reprogramming of somatic cells is the TGF-b pathway, which reads on inhibiting the TGFbeta R1 using small molecule compounds. Clarke et al. teach iPS cell generation has also been improved through the application of small molecules that target histone modifications, such as valproic acid which inhibit histone deacetylases (HDACs) (page 10, paragraph 3). Clarke et al. teach other small molecules for differentiation that include Forskolin (page 13, catalog number 1099), Tranylcypromine (page 15, catalog number 3852), TTNPB (page 15, catalog number 0761), SB431542 (page 15, paragraph 2), and LDN193189 (page 13, catalog number 6053) which reads on wherein the small molecule compounds comprises Forskolin, Tranylcypromine, Arotinoid Acid (TTNPB), and one or more of SB431542 and LDN193189. Clarke suggests the combination of small molecules in order to induce reprogramming (page 10, right column). Clarke et al. further teach dedifferentiation activity on cell types including dermal fibroblasts with high efficiency in vitro and in vivo(page 10, paragraph 2). Dermal fibroblasts could be obtained from various regions including the ear which makes obvious the somatic cells are ear fibroblasts.One of ordinary skill in the art would have been motivated to combine the transdifferentiation of somatic cells into mammary stem cells of Piccolo and Page with the introduction of a small molecule inhibitors including TGF-bR1 to produce histocompatible cells as taught by Clarke (page 10, paragraph 4). Clarke provides motivation by teaching the TGF-RI inhibitor enhances reprogramming efficiency (page 13, catalog number 3742) and combination of small molecules for reprogramming induction. There would be a reasonable expectation of success due to successful reprogramming of somatic cells in Piccolo et al. and Page et al. and the further enhancement of reprogramming taught by Clarke et al.
Response to Arguments
Applicant’s Argument: Applicant argues that amended claim 1 recites features that have not been disclosed, taught, or suggested by Piccolo. Applicant argues that Piccolo fails to disclose, teach, or suggest that a method for inducing transdifferentiation of somatic cells into mammary epithelial cells in vitro, wherein the somatic cells are ear fibroblasts or epidermal cells derived from a human being, a mouse, a rat, a rabbit, a pig, a sheep, a goat, a bovine, or a buffalo.
Response to Argument: Piccolo et al. teach a method for inducing transdifferentiation of somatic cells into mammary epithelial stem cells in vitro (page 2, paragraph 0020). Piccolo et al. teach the starting cell can be any mammalian cell, including, but not limited to, terminally differentiated cells. Piccolo further teaches the cell is a human cell, mouse cell, or rat cell. Piccolo does not teach the somatic cells are ear fibroblasts or epidermal cells. Page et al. teach a method of the present invention can be used to effect trans-differentiation of any type of somatic cell into any other type of somatic cell (page 2, paragraph 0012). Page teach examples of somatic cells that may be used or produced include fibroblasts or epidermal cells (page 2, paragraph 0012). The combination of the provided references make obvious the invention disclosed.
Applicant’s argument: Applicant argues that Clarke fails to disclose, teach, or suggest that inhibiting the TGFbeta R1 using small molecule compounds, wherein the small molecule compounds comprises valproic acid (VPA), Forskolin, Tranylcypromine, Arotinoid Acid (TTNPB), and one or more of SB431542, SB525334, and LDN193189. Clarke discloses small molecules valproic acid, Forskolin, Tranylcypromine, Arotinoid Acid, SB431542, SB525334 and LDN193189. However, Clarke did not publicly combine the use of valproic acid, Forskolin, Tranylcypromine, and Arotinoid Acid. In Claim 1, while valproic acid, Forskolin, Tranylcypromine, and Arotinoid Acid are used in combination, and choosing to use one or more combinations of SB431542, SB525334 and LDN193189. Only in this way can the effect produced in claim 1 be achieved. This is not made disclose by Clarke.
Response to Argument: Clarke does not explicitly state the small molecule compounds comprises a combination of valproic acid (VPA), Forskolin, Tranylcypromine, Arotinoid Acid (TTNPB). Clarke however suggests this combination in teaching the combinations of small molecules have also been shown to induce iPS cell reprogramming in the absence of all of the transcription factors from the four factor-method (page 10, right column).
Applicant’s Arguments: Applicant argues that claim 13 recites features that have not been disclosed, taught, or suggested by Clarke. Applicant argues the features “inhibiting the TGF beta R1 using gene interference, wherein gene interference includes the following steps: constructing a lentiviral recombinant plasmid pSicoR-Efla-mCh TGFBRI1 shRNA; co-transfecting 293T cells with the lentiviral recombinant plasmid pSicoR- Efla-mCh TGFBRI shRNA, Vesicular stomatitis virus-G (VSVG) and nuclear respiratory factor (NRF) for lentiviral packaging; and infecting fibroblasts with the packaged lentivirus;”. Applicant argues that Clarke fails to disclose, teach, or suggest that inhibiting the TGFbeta R1 using gene interference, wherein gene interference includes the following steps: constructing a lentiviral recombinant plasmid pSicoR-Efla-mCh TGFBR1 shRNA; co-transfecting 293T cells with the lentiviral recombinant plasmid pSicoR-Efla-mCh TGFBR1 shRNA, Vesicular stomatitis virus-G (VSVG) and nuclear respiratory factor (NRF) for lentiviral packaging; and infecting fibroblasts with the packaged lentivirus.
Response to Argument: Claim 13 is drawn to a non-elected invention and therefore cannot be examined as a part of the present invention.
Conclusion
THIS ACTION IS MADE FINAL. 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 Catherine L McCormick whose telephone number is (703)756-5659. The examiner can normally be reached Monday-Friday, 8:30 am-5:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635