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 2-25 are pending in the application. Claims 22-25 are withdrawn. Claims 2-21 are currently under examination.
This office action is in response to the amendment filed on 3/30/2026.
All previous rejection not reiterated in this office action are withdrawn.
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.
Claim 16 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 16 recites the limitation "the exogenous genes" in line 2. There is insufficient antecedent basis for this limitation in the claim because neither claim 2 nor claim 13 recites any exogenous genes.
This rejection is maintained because the amendment did not address this 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.
Claim 21 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This rejection is rewritten to address the amendment.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (a) the nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
The nature of the invention
Claim 21 is drawn to a method for treating a cancer that comprises a single step of introducing the herpes simplex virus with CCTCC deposit number of V201810, or an attenuated strain thereof, or a culture progeny thereof, into a subject suffering from cancer, wherein the cancer is liver cancer, melanoma, glioma, sarcoma, lung cancer, colorectal cancer, head and neck tumors, breast cancer, renal cell cancer, ovarian cancer, cervical cancer, prostate cancer, gastric cancer, lymphoma, pancreatic cancer, skin cancer for bladder cancer.
The breadth of the claim
The claim scope is rather broad. The claim encompasses treating a wide variety of cancer of different origin, etiology and metastatic potential by a single step of introducing the herpes simplex virus with CCTCC deposit number of V201810, or an attenuated strain thereof, or a culture progeny thereof, into a subject suffering from cancer, wherein the cancer is liver cancer, melanoma, glioma, sarcoma, lung cancer, colorectal cancer, head and neck tumors, breast cancer, renal cell cancer, ovarian cancer, cervical cancer, prostate cancer, gastric cancer, lymphoma, pancreatic cancer, skin cancer for bladder cancer.
The teaching from the specification and presence of working examples
The specification teaches HSV-1 is usually transformed into oncolytic simplex virus type 1 (oHSV-1) by means of genetic modification, and the main methods includes knocking out certain genes and inserting tumor therapy related genes, etc. (page 2, lines 42-43). The specification teaches the new HSV-1 isolate HL-1 (CCTCC V201810) has enhanced replication in human tumor cell lines, in the absence of ICP34.5 and/or ICP47, it has enhanced killing ability to tumor cells compared to an HSV-1 virus strain 17 (page 4, 1st paragraph). The specification provides working example 1 for isolating HL-1 strain, and example 2 demonstrates the oncolytic effects of wild strain HL-1 and strain 17 by transfecting a number of tumor cell line HepG2, A375, A549, MCF7, HeLa, U251 and Vero monkey kidney cells, wherein the transfection efficiency of HL-1 is significantly higher than that of HSV 17. However, the specification fails to teach whether administering HL-1 to cell in vitro, and/or in vivo enhanced replication and killing of any tumor cells. The specification also fails to teach how to treat cancer in an animal model or human subject by a single step of introducing HL-1, attenuated HL-1 or progeny thereof to said subject. The skilled artisan thus needs to look for guidance from prior art to practice the claimed method of treating cancer.
The state of prior art and the level of predictability in the art
The prior art is silent on a HSV-1 with a CCTCC deposit number of V201810. The state of prior art teaches a better understanding of the complex pattern of the interaction between HSV and host, and combination with current oHSV is essential to the refinements the strategy of oHSV to improve the therapeutic effects and to comprehend the oHSV immune imperfection (Ma et al. IDS, page 2, 2nd col., 2nd paragraph). Ma teaches the key to eradicate tumors with oHSV is to improve the precision when targeting oHSV for tumors, and enhance suppression, which involves genetic engineering of key genes in healthy cells that replicate with the virus (page 4, 2nd col., 4th paragraph, and Table 2). Ma teaches that the application of oHSV still have some problems that limits its therapeutic effect because the delivery by intratumoral or intravenous injection each has its own problem, difficult to spread to the lesion area outside the injection area, and innate immune response respectively. Based on the knowledge from prior art, whether a wild strain virus isolated from HSV fluid may be used to treat a wide variety of cancer as claimed would have been unpredictable.
The amount of experimentation needed to practice the invention
As discussed above, the teaching from the specification is limited to increased transfection efficiency for the HL-1 in a number of tumor cell lines, but not any therapeutic effect achieved in cells in vitro, animal model and human subject. The prior art does not provide any teaching with regard to HL-1 strain of HSV-1, but recognizes oHSV still has many hurdles to overcome including attenuated efficacy due to deletion of genes confer safety and selectivity, route of delivery, and physical factors like the extracellular matrix, and inborn and acquired anti-virus immunity (page 8, 1st col., 3rd paragraph of Ma et al). In view of limited teaching from the specification and the unpredictability exists in the art of HSV-1 therapy, an ordinary skilled in the art would have to engage in undue experimentation to practice the method as claimed. Therefore, the specification fails to provide sufficient teaching to enable a skilled artisan to practice the method as claimed.
Response to Arguments
Applicant argues that the specification provides more than ample guidance on how to implement the presently claimed methods of treating the recited cancers. Applicant states that example 2 demonstrates the oncolytic effects of wild strain HL-1 and strain 17 by transfecting a number of tumor cell line HepG2, A375, A549, MCF7, HeLa, U251 and Vero monkey kidney cells, wherein the transfection efficiency of HL-1 is significantly higher than that of HSV 17. Applicant states that the IC50 value of HL-1 and HSV when transfecting cells were all smaller than those HSV17. Applicant states that the viral strain HL-1 had better infection efficiency and replication ability in cells, and stronger oncolytic effect. Applicant states that example 4 demonstrates the HL-1 recombinant virus with inserted IL-12, GM-CSF or anti-PD-1 gene had better infection efficiency, replicating ability and stronger tumor oncolysis and better application prospects s oncolytic virus. Applicant concludes such teaching enables the claimed invention.
The above argument has been fully considered but deemed unpersuasive. With regard to the teaching from example 4, applicant is reminded that the claimed method is directed to using a virus strain with a CCTCC deposit number V201810 or an attenuated strain or a cultured progeny. As disclosed in the specification, this wild type virus does not have IL12, GM-CSF or anti-PD-1 insertion. As such, the teaching from example 4 does not enable the claimed method of claim 21 that uses virus strain with a CCTCC deposit number V201810 or an attenuated strain or a cultured progeny. With regard to the teaching from example 2, it demonstrates the oncolytic effects of wild strain HL-1 and strain 17 by transfecting a number of tumor cell line HepG2, A375, A549, MCF7, HeLa, U251 and Vero monkey kidney cells, wherein the transfection efficiency of HL-1 is significantly higher than that of HSV 17. Applicant states that the IC50 value of HL-1 and HSV when transfecting cells were all smaller than those HSV17. However, the effect is demonstrated in cell lines, which does not take into the consideration of the art recognized unpredictability for in vivo treating of cancer in a subject due to immune response and effective delivery that exists in a live animal and human subject. Therefore, for reasons discussed in previous rejection and set forth above, this rejection is still considered proper and thus maintained.
Allowable Subject Matter
Claim 2-15, 17-20 are allowed.
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 CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637
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