DETAILED ACTION
The amendment filed 08/13/2025 is acknowledged and has been entered.
Claims 1, 3-10, 12-13, 15 are currently pending.
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 .
Claim Rejections - 35 USC § 112
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.
Claims 1, 3, 5-6, 8, 10 are 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 1 recites the limitation "the micro-RNA encoding DNA segment" (emphasis added for clarity) in lines 3, 4, 5, 11, and 15. There is insufficient antecedent basis for this limitation in the claim because the claim does not recite “DNA segment” prior to the first recitation of “the micro-RNA encoding DNA segment”. It is noted that that claim 1 does recite “DNA fragment encoding a microRNA”, thus amending “DNA segment” to “DNA fragment” would obviate the rejection.
Claim 3 recites the limitation "the micro-RNA segment" in line 1. There is insufficient antecedent basis for this limitation in the claim. It is noted that claim 1 does recite “the micro-RNA encoding DNA segment”, which may be changed to “the micro-RNA encoding DNA fragment” as indicated above. It is recommended that claim 1 be amended to “the micro-RNA encoding DNA fragment” as indicated above, and then claim 3 may similarly be amended from “the micro-RNA segment” to “the micro-RNA encoding DNA fragment” to obviate the rejection.
Claim 5 recites the limitation "the micro-RNA encoding DNA segment" (emphasis added for clarity) in line 1. There is insufficient antecedent basis for this limitation. It is noted that that claim 1 does recite “DNA fragment encoding a microRNA”, thus amending “the micro-RNA encoding DNA segment” to “the micro-RNA encoding DNA fragment” would obviate the rejection.
Claim 6 recites the limitation "the micro-RNA segment" in line 1. There is insufficient antecedent basis for this limitation. It is noted that that claim 1 does recite “DNA fragment encoding a microRNA”, thus amending “the micro-RNA segment” to “the micro-RNA encoding DNA fragment” would obviate the rejection.
Claim 8 recites the limitation "the micro-RNA encoding DNA segment" (emphasis added for clarity) in line 1. There is insufficient antecedent basis for this limitation. It is noted that that claim 1 does recite “DNA fragment encoding a microRNA”, thus amending “the micro-RNA encoding DNA segment” to “the micro-RNA encoding DNA fragment” would obviate the rejection.
Claim 10 recites the limitation "the micro-RNA encoding DNA segment" (emphasis added for clarity) in lines 7, 8, and 9. There is insufficient antecedent basis for this limitation in the claim It is noted that that claim 10 does recite “DNA fragment encoding a microRNA”, thus amending “the micro-RNA encoding DNA segment” to “the micro-RNA encoding DNA fragment” would obviate the rejection.
In the interest of compact prosecution the claims will be interpreted as if there were proper antecedent support for the claim limitations.
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 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3-8, 10, 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Cubillos-Ruiz et al. (Cancer Res. (2012) 72:1683-1693; of record) in view of U.S. 2016/0008397 (hereafter “Krams”; of record) and Zhu et al. (International Journ. Mol. Med (2012), vol. 30: 1321-1326; of record); and further in view of US20150359867A1 (hereafter “Yu”).
Cubillos-Ruiz et al. teaches administering miR-155 directly to dendritic cells in vivo for immunotherapy of ovarian cancer wherein the method comprises delivering Dicer substrate RNA duplexes that mimic the structure of endogenous precursor miR-155 hairpin to dendritic cells in vivo at the site of a tumor (e.g., see abstract, paragraph bridging pages 1683-1684, etc.). Cubillos-Ruiz et al. teaches that the miR-155 sequence is administered using a polyethylenimine (PEI) based nanoparticle (e.g., see paragraph bridging pages 1683-1684, page 1684 second column, etc.). If necessary, Official Notice is taken that PEI is a cationic polymer.
Cubillos-Ruiz et al. does not teach amplifying a DNA fragment encoding the miRNA, sub-cloning the miRNA-encoding DNA into a delivery vehicle, such as a lentiviral vector, delivering the miRNA-encoding DNA into the cell via the delivery vehicle, injecting the cell into a tumor microenvironment (TME), or that the miRNA sequence comprises a miRNA stem loop structure, or administration in conjunction with a dendritic cell vaccine.
However, isolating dendritic cells (DCs), transfecting the isolated DCs with nucleic acid sequences, including expression constructs and viral vectors which express miRNAs, and then transplanting the transfected DCs into a patient (i.e., ex vivo) for treatment was well known in the prior art.
For instance, Krams teaches methods comprising isolating DCs from a subject, transfecting the DC cells with miRNA molecules or expression constructs which express the miRNAs, including viral vectors wherein the virus can be a lentivirus, and injecting the transfected DCs back into the patient (i.e., ex vivo administration of the DC which produces (i.e., “forms”) the miRNA in the subject). Krams teaches producing expression constructs which express the miRNA, including a viral vectors, such as lentiviral vectors. Krams teaches that the expression constructs comprising the miRNA can be transfected into DCs by known means, including electroporation. (For example, see abstract, paragraphs [0010], [0013], [0018], [0024], [0062]. [0122], [0124], claims 1-12, etc.).
Furthermore, the lentiviral vector PWPI was used in the prior art to deliver and expresses nucleic acids of interest, including miRNAs, in cells in vivo. For instant Zhu et al. teaches using pWPI to express a miRNA, and includes steps of amplifying a DNA fragment containing a miRNA comprising a pri-miR sequence (i.e., a stem-loop structure comprising the miR) and sub-cloning the pri-miR sequence into the vector and transferring the miRNA expressing PWPI vector into cells.
Additionally, dendritic cell vaccines for the treatment of ovarian cancer were known in the art. For instance, Yu teaches methods for treating ovarian cancers using dendritic cell (DC) vaccines (e.g., see abstract, claims 11 and 22, etc.).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the filing date of the instant invention, to combine the teachings of Cubillos-Ruiz et al., Krams, Zhu et al., and Yu to arrive at the claimed invention with a reasonable expectation of success. That is, one of ordinary skill in the art would have known to combine the cited references to make a lentiviral viral vector that expresses microRNA-155, transfer the viral vector into a DC (which is a bone marrow derived cell) and the administer the DC cell in combination with a DC cancer vaccine to an ovarian tumor site in a subject such that the DC cell expresses (i.e., forms) microRNA-155 ex vivo. The reason to do so would be to combine what was previously known in the art to treat ovarian cancer. The positive results of the cited prior art provides a reasonable expectation of success.
With respect to the limitation “wherein the microRNA segment increases efficacy of the at least one dendritic cell vaccine”, it is noted that this a functional limitation and performing the claimed method steps would necessarily have the same results including increasing efficacy of the dendritic cell vaccine.
It is noted that KSR forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http://www.uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
The combination of prior art cited above in the rejection(s) under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 USPQ2d 1385 (2007): “Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.”
Therefore, the claimed invention is not patentable in view of the prior art.
It is noted that claims 9 and 15 are not included in the rejection because they limit the tumor that is being suppressed to a breast cancer tumor. Therefore, amending claim 1 and 10 to limit the tumor to breast cancer tumor would obviate this rejection.
Non-Statutory 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3-10, 12-13, 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,537,625 (of record). Although the claims at issue are not identical, they are not patentably distinct from each other. The instant claims are broader in scope and fully encompass the claimed invention of the ‘625 patent, except with respect to the limitations requiring that the microRNA-encoding DNA is administered to a subject in conjunction with at least one dendritic cell vaccine. It is noted that limitations that are broader in scope are anticipated by narrower embodiments which they fully encompass. As such, the broader limitations of the instant claims are anticipated by the narrower claims of the ‘625 patent. With respect to the new limitations requiring that the microRNA segment is administered to a subject in conjunction with at least one dendritic cell vaccine, although the claims of the ‘625 patent do not explicitly require administration of a dendritic cell vaccine, the patented claims broadly encompass administration of other therapeutic agents. Using the specification of the issued patent as a dictionary to define the broad embodiments encompassed by the claims, it is clear that the specification indicates that a dendritic cell vaccine can also be administered to the subject. For instance, column 18, lines 5-25 indicates administration of a DC vaccine in conjunction with miR-155. Therefore, the instant claims are an obvious variation of the claimed method of the issued patent.
Claims 1, 3-10, 12-13, 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,071,753. Although the claims at issue are not identical, they are not patentably distinct from each other. The instant claims are broader in scope and fully encompass the claimed invention of the ‘753 patent, except with respect to the limitations requiring that the microRNA-encoding DNA is administered to a subject in conjunction with at least one dendritic cell vaccine. It is noted that limitations that are broader in scope are anticipated by narrower embodiments which they fully encompass. As such, the broader limitations of the instant claims are anticipated by the narrower claims of the ‘753 patent. With respect to the new limitations requiring that the microRNA segment is administered to a subject in conjunction with at least one dendritic cell vaccine, although the claims of the ‘753 patent do not explicitly require administration of a dendritic cell vaccine, the patented claims broadly encompass administration of other therapeutic agents. Using the specification of the issued patent as a dictionary to define the broad embodiments encompassed by the claims, it is clear that the specification indicates that a dendritic cell vaccine can also be administered to the subject. For instance, column 18, lines 5-25 indicates administration of a DC vaccine in conjunction with miR-155. Therefore, the instant claims are an obvious variation of the claimed method of the issued patent.
Response to the Amendment
With respect to the rejection of claims under 35 USC 112(b) as set forth in the previous office action, the amendment to the claims obviates the rejection. However, in view of the amended claims a new rejection under 35 USC 112(b) is set fort for the reasons indicated above.
With respect to the Non-Statutory Double Patenting rejections, Applicant's arguments have been fully considered but they are not persuasive. Applicant argues that Applicant’s method isolates dendritic cells and cancer cells from a breast cancer patient, and further preparing a dendritic cell vaccine by introducing a viral vector having a micro-RNA-155-encoding DNA into the isolated dendritic cells and treating the manipulated dendritic cells with cell lysate made from the isolated breast cancer cells.
In response, it is noted that the features upon which applicant relies (i.e., isolating dendritic cells and cancer cells from the breast cancer patient and treating the manipulated dendritic cells with cell lysate from the isolated breast cancer cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues that Cubillos-Ruiz does not teach manipulation of dendritic cells ex vivo and argues that Cubillos-Ruiz is directed to ovarian cancer which is an entirely separate cancer from breast cancer.
Applicant argues that Krams uses a different micro-RNA and modifies dendritic cells to suppress immune response.
Applicant argues that Zhu is directed to making liver cancer cells overexpress microRNA-29a.
Applicant argues that Yu teaches injection of multiple peptides to enhance immune response against ovarian cancer.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Furthermore, the rejected claims are not drawn to treating breast cancer. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Therefore, Applicant’s arguments are not persuasive and the claims stand rejected under 35 USC 103 for the reasons indicated above.
With respect to the Non-Statutory Double Patenting rejections, it is noted that Applicant has not present any arguments against these rejections. Therefore the claims stand rejected for the reasons set forth above.
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 J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00).
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL, Ph.D./ Primary Examiner, Art Unit 1637