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 .
This is in response to Applicant’s papers filed 11/25/2025.
Claims 1-4, 6-7, 9, 11, 13, 15, 19, 22, 25, 28-30, 33, 36, 41, 46, 48 and 52-59 are pending in the application. Claims 52-59 are newly added, claims 1-2, 7, 9, 11, 13, 15, 19, 22, 25, 28, 30, 33, 36, 41, 46, and 48 are amended, and no claims are canceled as set forth in the claim set filed 11/25/2025.
Therefore, claims 1-4, 6-7, 9, 11, 13, 15, 19, 22, 25, 28-30, 33, 36, 41, 46, 48 and 52-59 are examined on the merits.
Priority
This application is a 371 of PCT/US2021/026873 filed April 12, 2021.
Applicant’s claim for the benefit of provisional applications 63/121,777 filed 12/04/2020 and 63/009,218 filed 04/13/2020 is acknowledged.
Thus, the earliest possible priority date for the instant application is April 13, 2020.
Response to arguments
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 102
Claim(s) 1, 3, 4, 6, 7, 9, 11, 13, 15, 19, 22, 25, 28, 30, 33, and 46 remain rejected and 52-55 are newly rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mendlein (WO2018195338A1).
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/25/2025.
Regarding claims 1, 3, 4, and 6, Mendlein teaches utilizing one or more immunomodulatory agents such as cytokine and/or cytokine receptor inhibitors in addition to a viral therapeutic vector delivering a therapeutic polypeptide product (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 18, 2nd to last paragraph). The one or more cytokine and/or cytokine receptor inhibitors include anakinra and tocilizumab (i.e. IL-1R antagonist/signal inhibitor and IL-6 receptor antagonist) (p. 3-4, bridging paragraph). Moreover, the vector utilized can be adenoviral vectors, herpes virus vectors, vaccinia virus vectors, adeno- associated virus (AAV) vectors, and retroviral vectors (p. 20, 2nd paragraph).
Regarding claim 7, Mendlein teaches that the one or more immunomodulatory agents include steroids such as dexamethasone (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3, 1st paragraph).
Regarding claim 9, Mendlein teaches that the one or more immunomodulatory agents include calcineurin inhibitor such as tacrolimus (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3, 2nd paragraph)
Regarding claim 11, Mendlein teaches that the one or more immunomodulatory agents include TNF-alpha inhibitors such as etanercept (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3-4, bridging paragraph).
Regarding claim 13, Mendlein teaches that the one or more immunomodulatory agents include kinase inhibitors (JAK signal inhibitors) such as baricitinib, tofacitinib, ruxolitnib, and filgotinib (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 4, 1st paragraph).
Regarding claim 15, 19, 22, and 25, as discussed above, Mendlein teaches utilizing one or more immunomodulatory agents such as cytokine and/or cytokine receptor inhibitors in addition to a viral therapeutic vector delivering a therapeutic polypeptide product (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 18, 2nd to last paragraph). The one or more cytokine and/or cytokine receptor inhibitors include anakinra and tocilizumab (i.e. IL-1R antagonist/signal inhibitor and IL-6 receptor antagonist) (p. 3-4, bridging paragraph). Regarding claim 7, Mendlein teaches that the one or more immunomodulatory agents include steroids such as dexamethasone (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3, 1st paragraph). Additionally, Mendlein teaches that the one or more immunomodulatory agents include calcineurin inhibitor such as tacrolimus, TNF-alpha inhibitors such as etanercept, kinase inhibitors (JAK signal inhibitors) such as baricitinib, tofacitinib, ruxolitnib, and filgotinib (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3-4,). These immunomodulatory agents with the vector are disclosed as active ingredients/agents and Mendlein teaches an effective daily dose of the active agents can be administered in a single dose or multiple in either daily, weekly or monthly intervals (p. 110, 2nd to last paragraph; p. 114, 2nd to last paragraph). Therefore, the IL-1R antagonist anakinra and IL-6 receptor antagonist tocilizumab, dexamethasone tacrolimus, baricitnib, tofacitinib, ruxolitnib, and filgotinib are administered on the same day together with the vector.
Regarding claim 28, although Mendlein does not teach the specific results compared to controls that are claimed, Mendlein teaches each and every method step and limitation of the claims on which claim 28 depends and therefore, the same method steps yield the same results.
Regarding claim 30, Mendlein teaches that the vectors can transfer or encode a selectable marker so that transduced cells can be identified and generated (p. 20, 2nd paragraph).
Regarding claim 33, Mendlein teaches that the composition comprising the vector and immunomodulatory agents is formulated to be suitable for intravenous and subcutaneous injection (p. 109, 3rd paragraph, Example 1).
Regarding claim 46, Mendlein teaches that the term ‘subject’ in their invention is a mammalian subject such as a human (p. 24, line 9).
Regarding claim 52, Mendlein teaches that the one or more immunomodulatory agents include steroids such as dexamethasone (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3, 1st paragraph).
Regarding claim 53-55, Mendlein teaches that the one or more immunomodulatory agents include calcineurin inhibitor such as tacrolimus, TNF-alpha inhibitors such as etanercept, kinase inhibitors (JAK signal inhibitors) such as baricitinib, tofacitinib, ruxolitnib, and filgotinib (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3-4).
Therefore, the invention is anticipated by the time of the effective filing date.
In response to Applicant’s arguments and amendments filed 11/25/2025 regarding the 102 rejection,
Applicant’s arguments and amendments have been considered, however they are not persuasive.
Applicant argues that Mendlein provides only a laundry list of immunomodulatory agents with only three tested and enabled for in the examples, none of which are claimed in the present invention. Moreover, Applicant argues that the combination of adenovirus gene vector and IL-1 signal inhibitors and IL-6 receptor agonists is not demonstrated and there is an indeterminate number of pages of immunomodulatory agents to choose from.
The examiner disagrees. Mendlein states that one or more immunomodulatory agents such as cytokine and/or cytokine receptor inhibitors in addition to a viral therapeutic vector delivering a therapeutic polypeptide product can be utilized together in a method of therapy (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 18, 2nd to last paragraph). Mendlein additionally states one or more cytokine and/or cytokine receptor inhibitors include anakinra and tocilizumab (i.e. IL-1R antagonist/signal inhibitor and IL-6 receptor antagonist) (p. 3-4, bridging paragraph). Moreover, the vector utilized can be adenoviral vectors (p. 20, 2nd paragraph). This provides teachings which anticipate the claimed invention. Enablement provided by a disclosure is not necessary to show anticipation of an invention.
Moreover, the instant claims require administering to the subject of an interleukin-1 (IL-1) signal inhibitor, an interleukin-6 (IL-6) receptor antagonist and an adenoviral vector therapy, but the instant claims are not so limited such that this is the only possible regimen of administration. The claims are "open" and thus lend themselves to additional combinations of immunomodulatory agents and transgenes with a viral gene therapy vector. There is no requirement that the only combination of an IL-1 signal inhibitor and an IL-6 receptor antagonist and an adenoviral vector of instant claim 1 is so limited as argued by Applicant. Thus, the disclosure of Mendlein additionally anticipates the instant invention, since of Mendlein discloses combination of an IL-1 signal inhibitor and an IL-6 receptor antagonist and an adenoviral vector.
Claim Rejections - 35 USC § 103
Claim(s) 1-4, 6, 7, 9, 11, 13, 15, 19, 22, 25, 28-30, 33, 36, 41, 46 and 48 remain rejected and 52-55 are newly rejected under 35 U.S.C. 103 as being unpatentable over Mendlein (WO2018195338A1; IDS Reference filed 07/11/2024) in view of Richter (Hematol Oncol Clin N Am 31 (2017) 771–785).
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/25/2025.
Regarding claims 1, 3, 4, and 6, Mendlein teaches utilizing one or more immunomodulatory agents such as cytokine and/or cytokine receptor inhibitors in addition to a viral therapeutic vector delivering a therapeutic polypeptide product (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 18, 2nd to last paragraph). The one or more cytokine and/or cytokine receptor inhibitors include anakinra and tocilizumab (i.e. IL-1R antagonist/signal inhibitor and IL-6 receptor antagonist) (p. 3-4, bridging paragraph). Moreover, the vector utilized can be adenoviral vectors, herpes virus vectors, vaccinia virus vectors, adeno- associated virus (AAV) vectors, and retroviral vectors (p. 20, 2nd paragraph).
Regarding claims 2, 29, and 41, Mendlein does not explicitly teach the transduction of stem cells in particular, the mobilization of stem cells, and delivery of payload into the genome of the stem cell.
Richter teaches administering in vivo therapy through the combination of intravenous injection after the mobilization of HSCs through subcutaneous injections of GSCF/AMD3100 (Figure 1; p. 2, last paragraph; p. 8, 2nd paragraph). In Richter’s studies, the in vivo transduction utilizing this method with HDAd5/35 vectors showed that the gene was integrated into the stem cell genome (p. 8, 2nd paragraph). HSC gene therapy’s goal is the lifelong correction of an underlying genetic disease and HSC in vivo gene therapy approaches aim to simplify the gene therapy process by eliminating the need for ex vivo handling of patient HSCs (Synopsis; p. 7, last paragraph).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to administer the vector of Mendlein with all of the immunomodulatory agents claimed to a subject receiving in vivo therapy and transduce the subject’s HSCs when combined with a mobilizing agent such as G-CSF with a reasonable expectation of success. An artisan would be motivated to utilize Mendlein’s vector and immunomodulatory agents with a mobilization regime as Richter teaches HSC gene therapy’s goal is the lifelong correction of an underlying genetic disease and HSC in vivo gene therapy approaches aim to simplify the gene therapy process by eliminating the need for ex vivo handling of patient HSCs (Synopsis; p. 7, last paragraph). Combining a viral vector with a mobilization regime is an in vivo gene therapy method which is known in the art as taught by Richter (Figure 1). Therefore, the payload would be delivered to the stem cells with a reasonable expectation of success.
Regarding claim 7, Mendlein teaches that the one or more immunomodulatory agents include steroids such as dexamethasone (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3, 1st paragraph).
Regarding claim 9, Mendlein teaches that the one or more immunomodulatory agents include calcineurin inhibitor such as tacrolimus (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3, 2nd paragraph)
Regarding claim 11, Mendlein teaches that the one or more immunomodulatory agents include TNF-alpha inhibitors such as etanercept (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3-4, bridging paragraph).
Regarding claim 13, Mendlein teaches that the one or more immunomodulatory agents include kinase inhibitors (JAK signal inhibitors) such as baricitinib, tofacitinib, ruxolitnib, and filgotinib (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 4, 1st paragraph).
Regarding claim 15, 19, 22, and 25, as discussed above, Mendlein teaches utilizing one or more immunomodulatory agents such as cytokine and/or cytokine receptor inhibitors in addition to a viral therapeutic vector delivering a therapeutic polypeptide product (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 18, 2nd to last paragraph). The one or more cytokine and/or cytokine receptor inhibitors include anakinra and tocilizumab (i.e. IL-1R antagonist/signal inhibitor and IL-6 receptor antagonist) (p. 3-4, bridging paragraph). Regarding claim 7, Mendlein teaches that the one or more immunomodulatory agents include steroids such as dexamethasone (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3, 1st paragraph). Additionally Mendlein teaches that the one or more immunomodulatory agents include calcineurin inhibitor such as tacrolimus, TNF-alpha inhibitors such as etanercept, kinase inhibitors (JAK signal inhibitors) such as baricitinib, tofacitinib, ruxolitnib, and filgotinib (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3-4,). These immunomodulatory agents with the vector are disclosed as active ingredients/agents and Mendlein teaches an effective daily dose of the active agents can be administered in a single dose or multiple in either daily, weekly or monthly intervals (p. 110, 2nd to last paragraph; p. 114, 2nd to last paragraph). Therefore, the IL-1R antagonist and IL-6 receptor agonist, dexamethasone tacrolimus, baricitnib, tofacitinib, ruxolitnib, and filgotinib are administered on the same day together with the vector.
Regarding claim 28, although Mendlein does not teach the specific results compared to controls that are claimed, Mendlein teaches each and every method step and limitation of the claims on which claim 28 depends and therefore, the same method steps yield the same results.
Regarding claim 30, Mendlein teaches that the vectors can transfer or encode a selectable marker so that transduced cells can be identified and generated (p. 20, 2nd paragraph).
Regarding claim 33, Mendlein teaches that the composition comprising the vector and immunomodulatory agents is formulated to be suitable for intravenous and subcutaneous injection (p. 109, 3rd paragraph, Example 1).
Regarding claim 36, Mendlein does not teach where the adenoviral vector is derived from or is an Ad5/35 or Ad35 adenoviral vector. However, Ritcher teaches in vivo transduction with HDAd5/35 vectors which showed that the gene was integrated into the stem cell genome (p. 8, 2nd paragraph). Therefore, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to utilize an Ad5/35 vector as an artisan would know it effectively integrates into the cell genome.
Regarding claim 46, Mendlein teaches that the term ‘subject’ in their invention is a mammalian subject such as a human (p. 24, line 9).
Regarding claim 48, Mendlein does not teach specifically that the dosing regimen of immune suppression agents is increased based on immunotoxicity levels. However, Mendlein teaches “a physician having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician could start doses of the HRS polypeptides/expressible polynucleotides and/or immunomodulatory agents employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.” Therefore, it would be obvious to one of ordinary skill in the art to optimize the parameters and base the immunomodulatory agents and viral vectors on the level of therapeutic effect an artisan would want to achieve and as taught by increase the pharmaceutical composition levels. As disclosed in the instant specification, immunotoxicity can be an inflammatory response or cytokine response, therefore, when such a parameter is measured, optimizing the levels of a cytokine inhibitor would be obvious to one of ordinary skill in the art.
Regarding claim 52, Mendlein teaches that the one or more immunomodulatory agents include steroids such as dexamethasone (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3, 1st paragraph).
Regarding claim 53-55, Mendlein teaches that the one or more immunomodulatory agents include calcineurin inhibitor such as tacrolimus, TNF-alpha inhibitors such as etanercept, kinase inhibitors (JAK signal inhibitors) such as baricitinib, tofacitinib, ruxolitnib, and filgotinib (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 3-4).
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
In response to Applicant’s arguments and amendments filed 11/25/2025 regarding the 102 rejection,
Applicant’s arguments and amendments have been considered, however they are not persuasive.
Applicant argues that there is an unexpected finding that an IL-1 signal inhibitor and IL-6 receptor agonist can abrogate immunotoxicity by adenoviral vector administration and that neither references teach the combination’s advantageous effects.
The examiner states that evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). “A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference.” In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential). See also MPEP 716.02e.
Moreover, in response to applicant's argument that advantageous effects or combinations are not explicitly stated in the referencs, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
New objections/ Rejections in response to Applicants’ arguments or amendments
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 15, 22, 25, 33, 36, 41, 48, 56, and 59 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.
Claims 15, 22, 25, 33, 36, 41 and 48 recite the term “and/or.” It is unclear what the metes and bounds of this term, as “and” could be interpreted to include only one option or all options, or, “or” would imply that the options/steps are in the alternative. Appropriate correction is required.
The term “selecting agent” in claim 59 renders the claim indefinite. The term “selecting agent” is not defined by the claim and the only selecting agent disclosed by the application is O6BG/BCNU.
Claim 48 is rejected because of the recitation of “the dosing regimen”. There is not proper antecedent bases for “the dosing regimen” in the claim.
New grounds of objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 56-57 are newly rejected under 35 U.S.C. 103 as being unpatentable over Mendlein (WO2018195338A1; IDS Reference filed 07/11/2024) as applied to claims 1, 15 and 19 above, and further in view of Keidel (Rheumatology 2014;53:573574).
Regarding claims 1, 15 and 19, Mendlein teaches utilizing one or more immunomodulatory agents such as cytokine and/or cytokine receptor inhibitors in addition to a viral therapeutic vector delivering a therapeutic polypeptide product for the treatment of inflammation (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 18, 2nd to last paragraph). The one or more cytokine and/or cytokine receptor inhibitors include anakinra and tocilizumab (i.e. IL-1R antagonist/signal inhibitor and IL-6 receptor antagonist) (p. 3-4, bridging paragraph). Moreover, the vector utilized can be adenoviral vectors, herpes virus vectors, vaccinia virus vectors, adeno- associated virus (AAV) vectors, and retroviral vectors (p. 20, 2nd paragraph).
However, Mendlein does not teach the dosage of the anakinra or the tocilizumab.
Keidel teaches utilizing anakinra at a dose of 100 mg/day and tocilizumab at a dose of 8mg/kg/month in a teen subject with an inflammatory disorder (p. 573, 2nd column). If the average weight of a teen woman is 50kg, this would be approximately 13 mg/day of tocilizumab.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to utilize anakinra at a dose of 100 mg/day and 13 mg/day of tocilizumab in the method of Mendlein with a reasonable expectation of success. An artisan would have been motivated to do so as Keidel demonstrates that the dosages are known in the art to treat inflammatory conditions.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Claims 58-59 are newly rejected under 35 U.S.C. 103 as being unpatentable over Mendlein (WO2018195338A1; IDS Reference filed 07/11/2024) as applied to claims 1 and 30 above, and further in view of Ball (Blood (2004) 104 (11) : 2109.)
Regarding claims 1 and 30, Mendlein teaches utilizing one or more immunomodulatory agents such as cytokine and/or cytokine receptor inhibitors in addition to a viral therapeutic vector delivering a therapeutic polypeptide product for the treatment of inflammation (p. 1, Brief Summary; p. 2, 2nd to last paragraph; p. 18, 2nd to last paragraph). The one or more cytokine and/or cytokine receptor inhibitors include anakinra and tocilizumab (i.e. IL-1R antagonist/signal inhibitor and IL-6 receptor antagonist) (p. 3-4, bridging paragraph). Moreover, Mendlein teaches that the vectors can transfer or encode a selectable marker so that transduced cells can be identified and generated (p. 20, 2nd paragraph). The vector utilized can be adenoviral vectors, herpes virus vectors, vaccinia virus vectors, adeno- associated virus (AAV) vectors, and retroviral vectors (p. 20, 2nd paragraph).
However, Mendlein does not teach administering to the subject a selecting agent such as O6BG/BCNU or that the selectable marker is MGMTP140K.
Ball teaches bone marrow cells from mice transduced with an MGMT/IRES/eGFP encoding retroviral vector and transplanted into recipient mice. Starting 4 weeks post-transplant, the mice were treated monthly with two reduced dosages of O6 BG and BCNU (p. 2) Overall, “successful selection of gene modified hematopoietic stem cells against the majority of non-modified cells may increase the efficiency and safety of clinical gene therapy. Especially if a reduction of the intensity of the myelotoxic pre-transplant conditioning treatment is sought, selection of the initially low percentage of retrovirally gene modified stem cells is required. In addition to the decreased drug related toxicity, such a procedure reduces the risk of genotoxicity caused by insertional mutagenesis simply by diminishing the likelihood of transplanting stem cells that carry unwanted insertion sides compared to strategies that attempt to increase efficiency by increasing vector dose and/or the number of engrafted gene-modified cells. To date, the mutant O6-methylguanine-DNA methyltransferase (MGMT) enzyme that confers resistance to nitrosoureas such as BCNU is the drug-resistance gene that allows most efficient selection at the stem cell level.” (p. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer to the subject a selecting agent such as O6BG/BCNU and encode a selectable marker such as MGMTP140K with a reasonable expectation of success. An artisan would have been motivated to utilize both the agent and the marker as successful selection of gene modified hematopoietic stem cells against the majority of non-modified cells may increase the efficiency and safety of clinical gene therapy as well as such a procedure which reduces the risk of genotoxicity caused by insertional mutagenesis.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
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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/ALEXANDRA F CONNORS/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634