DETAILED ACITON
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 .
Application Status
Applicant’s remarks, and amendments to the drawings, specification, and claims filed January 26, 2026 are acknowledged. Claims 1-2, 14, and 18 were amended. Claims 1-2, 5-6, 12, 14, 16-20, 22, 27, 31, 35, and 37-44 are pending.
Restriction/Election
Claims 5-6, and 38-44 remain withdrawn from further consideration pursuant to 37 C.F.R. 1.142(b) as being drawn to a non-elected invention. Claims 1-2, 12, 14, 16-20, 22, 27, 31, 35, and 37 are under examination herein.
Priority
Applicant’s claim for priority to Application Nos. 62/825,516, filed March 28, 2019, and PCT/US20/25217, filed March 27, 2020, is acknowledged. Claims 1-2, 12, 14, 16-20, 22, 27, 31, 35, and 37 find support in Application No. 62/825,516. The effective filing date of all claims under examination is March 28, 2019.
Withdrawn Rejections
Applicant’s remarks and amendments to the drawings, specification, and claims have been thoroughly reviewed. The amendments are sufficient to overcome the previous objections to the drawings, specification, and claims raised in the prior action. These have been withdrawn, accordingly. Applicant’s amendments to claim 1 to require that (a)-(b) occur “prior to the administering step” are sufficient to overcome the § 102 rejections raised in the prior action over Andrews. These rejections are withdrawn, accordingly.
Applicant’s remarks and amendments to the claims have been thoroughly considered, but are not found sufficient to place the claims in condition for allowance for the reasons that follow. Any objection or rejection not reiterated herein has been overcome by amendment.
Claim Objections
Claim 2 is objected to because of the following informalities:
Claim 2 recites “identifying methylated residues in MGMT in the subject.” The specification only describes identifying DNA methylation in the MGMT promoter in the subject (Fig. 3; [0013]; [0144]; Table 6), i.e., not methylation of the “residues in MGMT,” a phrase which would refer to the amino acids of MGMT protein. The claim should be amended, accordingly.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-2, 12, 14, 16-20, 22, 27, 31, 35, and 37 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. The rejections that follow are maintained and modified as necessitated by Applicant’s amendments to the claims.
Claim 1 recites “increased likelihood of responding to an IGF-1R AS ODN.” The phrase includes relative terminology, i.e., “increased,” and it is not clear what the likelihood must be increased relative to, e.g., other subjects with cancer, a reference value, etc. The claim and specification provide means to evaluate the likelihood of responding to an IGF-1R AS ODN, e.g., determining MGMT methylation in the subject prior to the administering step, but these means do not actually provide a standard for ascertaining the requisite degree of “increased likelihood.” Because it is not clear what constitutes an “increased likelihood,” a skilled artisan would not be reasonably apprised of the scope of the invention, and the claim is indefinite.
Claims 2, 12, 14, 16-20, 22, 27, 31, 35, and 37 are rejected for depending from claim 1 and failing to remedy the indefiniteness.
Claim 2 recites “good T cell function.” The term “good” is a relative term. The claim and specification state that “good T cell function” refers to subjects with “a median or greater number of T cells expressing IFN-γ in response to nonspecific stimulation” ([0008]). However, this description does not rescue the relative terminology. It is not clear how many T cells constitute “a median or greater” number of T cells expressing IFN-γ. Furthermore, the term “nonspecific stimulation” is not defined in the specification, and based on the art, the skilled artisan would understand that the number of responding T cells would differ based on the type and amount of stimulus used. Because it is not clear what constitutes “good” T cell function based on the claims or specification, a skilled artisan would not be reasonably apprised of the scope of the invention, and the claim is indefinite.
Response to Remarks - 35 USC § 112(b)
Applicant’s remarks regarding the § 112(b) rejections raised in the prior rejection have been reviewed. Applicant submits that the amendments to claims 1 and 2 resolve the rejections. Examiner respectfully disagrees. The amendments to claim 1 require that (a)-(b) be determined “prior to the administering step.” These amendments do not remedy the relative terminology, because as described above, the means do not actually provide a standard for ascertaining the requisite degree of “increased likelihood.” Claim 2 has been amended to recite a phrase (“a median or greater number of T cells expressing IFN-γ in response to nonspecific stimulation”) which attempts to define “good T cell function.” This phrase is evaluated in the prior action and above. The phrase does not rescue the relative terminology of “good T cell function,” because the phrase itself recites relative terminology (e.g., “median or greater number… nonspecific stimulation”). The rejections are maintained and modified, accordingly.
CLAIM INTERPRETATION
Claim 1 recites “A method of treating cancer, the method comprising identifying a subject having cancer and having an increased likelihood of responding to an…. []IGF-1R AS ODN[] and administering to the subject the IGF-1R AS ODN….” In view of the indefiniteness described above, the phrase “increased likelihood” will be interpreted as “likelihood.” Accordingly, the claim is interpreted as a method of treating cancer by identifying a subject having cancer, evaluating the likelihood of the subject responding to an IGF-1R AS ODN by determining MGMT methylation or determining T cell function in the subject, and, after determining, administering the IGF-1R AS ODN to the subject. The claim recites elements which could be considered abstract ideas (e.g., “identifying a subject…,” “evaluated by,” “determining MGMT methylation,” or “determining T cell function”) or natural phenomena (i.e., the correlation between response to an IGF-1R AS ODN and MGMT methylation levels or T-cell function). However, the claim also requires a particular treatment step (“administering to the subject the IGF-1R AS ODN”) which, therefore, renders the claim subject matter eligible. See MPEP 2106.04(d)(2).
Notice to Joint Inventors
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim Rejections - 35 USC § 103 – Andrews
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.
Claims 1-2, 12, 16-17, 27, 35, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record). The following rejections are new and necessitated by Applicant’s amendments to the claims.
Regarding claim 1, Andrews teaches a method of treating cancer comprising identifying a subject having cancer (see “Study Site and Patients”; Table 1), and administering an IGF-1R AS ODN to the subject (“subjects were treated by 24 hour implantation… of ten biodiffusion chambers containing irradiated autologous tumor cells and IGF-1R AS ODN”, pg. 7, “Abstract”; “the combination product consisted of autologous tumor cells removed at surgery then treated overnight with the IGF-1R AS ODN… prior to being added to semi-permeable chambers and irradiated… Study objectives included assessment of safety and radiographic responses as well as exploratory objectives looking at immune function and response”, pg. 7, “Study Design and Objectives”).
Andrews also teaches correlating the subject’s response to the administered IGF-1R AS ODN with the subject’s level of T-cell function (“pre-treatment assessments of immune function,” pg. 7; “Two significantly different protocol survival cohorts of 48.2 and 10 weeks were identified as longer and short survival cohorts, respectively (Figure 1A&B)”, pg. 9, left col.; “Levels of 24 of the 78 cytokines/chemokines were significantly higher in serum from the longer survival cohort compared to the short cohort”, pg. 9, middle col.; “the longer survival subjects manifested significantly higher Th-1 cytokine production including IFN-γ after stimulation”, pg. 9, right col.) and MGMT methylation (“The short survival cohort had longer overall survival perhaps in part due to MGMT methylation and better responses to temozolamide in three patients”, pg. 12, middle col.; Table 1 “IDH-1 mutation/MGMT methylation”). Thus, Andrews teaches determining MGMT methylation and/or T-cell function in the subject as a means to evaluate the likelihood the subject will respond to the IGF-1R AS ODN.
However, Andrews does not teach a method in which determining MGMT methylation and/or T-cell function in the subject as a means to evaluate the likelihood the subject will respond to the IGF-1R AS ODN occurs prior to the administration of the IGF-1R AS ODN.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have determined MGMT methylation and/or T-cell function in a subject with cancer, as a means to evaluate the likelihood the subject will respond to the IGF-1R AS ODN in view of Andrews. It would have amounted to measuring the levels of known survival marker(s) in a known method of treating cancer, by known means, to yield predictable results. The skilled artisan would have had a reasonable expectation of success because Andrews demonstrates that T cell function and MGMT methylation correlate with a subject’s likelihood to respond to an IGF-1R AS ODN. The skilled artisan would have been motivated to determine the levels of these know survival markers, prior to administering an IGF-1R AS ODNto a subject with cancer, because Andrews illustrates that the likelihood of a subject’s response to an IGF-1R AS ODN is correlated with the subject’s levels of MGMT methylation and T cell function, and the step(s) would, therefore, allow the skilled artisan to predict whether the subject would be a good candidate for the method taught by Andrews.
Regarding claim 2, in view of the indefiniteness described above, (b) is interpreted as determining T cell function in the subject, by assessing IFN-γ production in T cells after stimulation. As stated above, Andrews’ method involves determining T cell function in the subject, as assessed by IFN-γ production from T cells after stimulation, as a means to evaluate the likelihood the subject will respond to the IGF-1R AS ODN (“Levels of 24 of the 78 cytokines/chemokines were significantly higher in serum from the longer survival cohort compared to the short cohort”, pg. 9, middle col.; “the longer survival subjects manifested significantly higher Th-1 cytokine production including IFN-γ after stimulation”, pg. 9, right col.).
Regarding claim 12, as described above, Andrews teaches the T cell function is determined by evaluating the number of T cells expressing IFN-γ in response to stimulation (“the longer survival subjects manifested significantly higher Th-1 cytokine production including IFN-γ after stimulation”, pg. 9, right col.).
Regarding claim 16, the term “autologous cancer cell vaccine” is interpreted as a composition comprising tumor cells isolated from the subject, which may comprise additional components, e.g., IGF-1R AS ODN ([0022]). Andrews teaches the IGF-1R AS ODN is administered to the subject as an autologous cancer cell vaccine (“we report the results of a second Phase 1 autologous tumor cell vaccination trial for patients with recurrent glioblastomas,” pg. 7; “the combination product consisted of autologous tumor cells removed at surgery then treated over-night with the IGF-1R AS ODN (4mg/ml) prior to being added to semi-permeable chambers and irradiated. Enhancements to the vaccine product…, see “Study Design and Objectives,” pg. 7; “we have established the safety profile of an improved combination glioma vaccine product,” pg. 12).
Regarding claim 17, the term “biodiffusion chamber” is interpreted as an container which allows diffusion of factors, e.g., small molecules, but not cells, between the subject and chamber ([0051]). A “fully formulated biodiffusion chamber” is interpreted as a biodiffusion chamber that includes autologous tumor cells and other cells included in the tumor microenvironment that may be treated with IGF-1R AS ODN prior to encapsulation ([0023]). Andrews teaches administering the IGF-1R AS ODN to the subject as a fully formulated biodiffusion chamber (“the combination product consisted of autologous tumor cells removed at surgery then treated over-night with the IGF-1R AS ODN (4mg/ml) prior to being added to semi-permeable chambers and irradiated,” see “Study Design and Objectives,” pg. 7).
Regarding claim 27, Andrews teaches the sequence of the IGF-1R AS ODN (“5’-TCCTCCGGAGCCAGACTT-3’,” pg. 7), which is 100% identical to the sequence set forth in instant SEQ ID NO: 1 as shown in Fig. A below.
Figure A
TCCTCCGGAGCCAGACTT Andrews’ IGF-1R AS ODN
TCCTCCGGAGCCAGACTT SEQ ID NO: 1
Regarding claim 35, Andrews teaches the cancer is brain cancer (“we report the results of a second Phase 1 autologous tumor cell vaccination trial for patients with recurrent glioblastomas,” pg. 7).
Regarding claim 37, Andrews’ subjects are human subjects (see “Study Site and Patients”; Table 1).
Claim Rejections - 35 USC § 103 – Andrews in view of Pearson
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) as applied to claims 1-2, 12, 16-17, 27, 35, and 37, in view of Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record). The following rejection is new and necessitated by Applicant’s amendments to the claims.
The teachings of Andrews are described above and applied as to claims 1-2, 12, 16-17, 27, 35, and 37 therein.
Regarding claim 14, Andrews teaches that the subjects enrolled in the study failed standard therapies, which included treatment with temozolomide (pg. 7; “TMZ, Table 1). Andrews teaches that “resistance to treatments in gliomas [are] associated with activation of the IGF-1R signaling axis,” and that “IGF-1R inhibition… overcomes this resistance with improved outcomes.” Indeed, Andrews teaches that in their study, the short survival cohort had “longer overall survival,” perhaps owing to three patients having “MGMT methylation and better responses to temozolamide” (pg. 6, middle col.).
While Andrews teaches that IGF-1R inhibition can overcome treatment resistance, and illustrates improved outcomes and better responses to temozolomide in a cohort of subjects treated with the biodiffusion chambers, Andrews does not teach a method in which the IGF-1R AS ODN Is administered prior to temozolomide.
Pearson teaches that temozolomide is part of the “gold standard” treatment for subjects with glioblastoma (pg. 1, right col.). Pearson teaches that glioblastoma is “uniformly fatal” despite this multimodal aggressive therapy, and that accordingly, novel avenues for therapy are imperative (pg. 1, right col.). Pearson suggests new avenues, e.g., therapies targeting IGF-1R (Table 1). Pearson teaches that IGF-1R is overexpressed in glioblastoma, and this overexpression is linked to shorter survival and reduced responsiveness to temozolomide (pg. 2-4). Pearson teaches that an IGF-1R inhibitor has “shown promising anti-tumor properties” in temozolomide resistant glioblastoma cells (pg. 4, right col.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted Andrews’ method to administer the IGF-1R AS ODN-comprising biodiffusion chambers prior to administering temozolomide. It would have amounted to adapting the order of steps in a known method, by known means, to yield predictable results. Pearson teaches that temozolomide resistance can be overcome by IGF-1R inhibition. Andrews’ method employs an IGF-1R inhibitor (i.e., the IGF-1R AS ODN), and Andrews illustrates improved outcomes in a cohort of subjects treated with biodiffusion chambers comprising the IGF-1R inhibitor, owing in part to “better responses to temozolamide.” Accordingly, based on Andrews and Pearson, the skilled artisan would have had a reasonable expectation of success in adapting Andrews’ method to administer the IGF-1R AS ODN-comprising biodiffusion chambers prior to administering temozolomide. Pearson strongly encourages exploration of new therapeutic approaches for glioblastoma. The skilled artisan would have recognized that Andrews’ method employs an IGF-1R inhibitor with the potential to combat temozolomide resistance based on Pearson, and therefore, would have been motivated to adapt Andrews’ method to illicit better responses to this “gold standard” glioblastoma treatment.
Claim Rejections - 35 USC § 103 – Andrews in view of NIH Clinical Trials
Claims 18, 20, 22, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) as applied to claims 1-2, 12, 16-17, 27, 35, and 37, in view of NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record). The following rejections are new and necessitated by Applicant’s amendments to the claims.
Regarding claim 18, the claim recites steps through which the biodiffusion chamber administered in claim 17 is prepared, and therefore, the biodiffusion chamber of claim 18 and its dependents is interpreted as a product-by-process. MPEP 2113(I) states that product-by-processes are not limited to the manipulations of the recited steps, only the structure implied by the steps. In the case of claim 18, the structure implied by the steps is an irradiated biodiffusion chamber containing tumor cells isolated from the subject and an IGF-1R AS ODN, wherein the ratio of tumor cells to IGF-1R AS ODN in the chamber is within the recited range.
The teachings of Andrews are described above and applied as to claims 1-2, 12, 16-17, 27, 35, and 37 therein. Andrews teaches administering an irradiated biodiffusion chamber containing tumor cells isolated from the subject and an IGF-1R AS ODN (“the combination product consisted of autologous tumor cells removed at surgery then treated over-night with the IGF-1R AS ODN (4mg/ml) prior to being added to semi-permeable chambers and irradiated… Enhancements to the vaccine product included… addition of 2 mg of exogenous antisense to the chambers,” see “Study Design and Objectives,” pg. 7).
Andrews is silent as to the ratio of tumor cells to IGF-1R AS ODN in the chamber. However, Andrews states that the study corresponds to a Phase I clinical trial associated with ID: NCT01550523 (see “Background,” pg. 7).
NIH Clinical Trials (hereinafter, “NIH”) provides the study design for the clinical trial associated with ID: NCT01550523. Regarding the preparation of the biodiffusion chamber, NIH teaches that each chamber is loaded with 106 cells and contains 2µg of IGF-1R AS ODN (“Tumor cells will be incubated with IGF-1R/AS ODN for a maximum of 6 hours and 106 cells will [] then be loaded into each chamber and a target maximum of 10 chambers prepared,” pg. 8; “Patients will receive approximately 10 to 20 million IGF-1R/AS ODN treated tumor cells, encapsulated in diffusion chambers (maximum of 10)… Autologous tumor cells pretreated with the IGF-1R AS ODN and resuspended in 2ug of exogenous IGF-1R AS ODN are added to the chamber,” pgs. 11-12). Thus, NIH teaches that the biodiffusion chamber contains a ratio of tumor cells to IGF-1R AS ODN in the recited range (i.e., 106 : 2µg = 5 x 105 : 1µg).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the specific preparation steps taught by NIH to prepare the biodiffusion chamber in the method of Andrews. It would have amounted to applying known steps to prepare an element in a known method (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the biodiffusion chamber as taught by NIH because Andrews specifically references the disclosure of NIH, and NIH provides detailed instructions for preparing the generically described biodiffusion chamber of Andrews. The skilled artisan, seeking to prepare the biodiffusion chamber of Andrews in order to practice Andrews’ method, would have been motivated to utilize the specific preparation steps of NIH, because as stated directly above, Andrews’ disclosure corresponds to the Phase I clinical trial described by NIH.
Regarding claim 20, the phrase “enriched for adherent cells compared to tumor cells obtained from the subject” is interpreted as requiring that the tumor cells in the chamber be adherent cells, e.g., as demonstrated by attachment to a surface in cell culture. Andrews is silent as to whether the tumor cells are enriched for adherent cells as interpreted above. However, as stated above, Andrews references the Phase I clinical trial associated with ID: NCT01550523 (see “Background,” pg. 7).
Regarding the preparation of the biodiffusion chamber, NIH teaches that “viable tumor tissue [is] confirmed by pathologic examination of frozen sections, and then sent to a BL-2 facility for disaggregation and plating in culture” (pg. 8). NIH teaches that “once cells are attached, cells will immediately be treated with IGF-1R/AS ODN” (pg. 8). Thus, NIH teaches that the biodiffusion chamber contains cells which are enriched for adherent cells compared to tumor cells obtained from the subject.
The obviousness of utilizing the specific preparation steps taught by NIH to prepare the biodiffusion chamber in Andrews’ method is described in paragraph 36 above and applied here with respect to claim 20.
Regarding claim 22, Andrews teaches the cells are treated with IGF-1R AS ODN prior to encapsulation in the chamber (“the combination product consisted of autologous tumor cells removed at surgery then treated overnight with the IGF-1R AS ODN (4mg/ml) prior to being added to semi-permeable chambers and irradiated,” see “Study Design and Objectives,” pg. 7).
Regarding claim 31, Andrews teaches implanting two or more biodiffusion chambers into the subject (“subjects were treated by 24 hour implantation in the rectus sheath of ten biodiffusion chambers containing irradiated autologous tumor cells and IGF-1R S ODN,” see “Methods,” pg. 7).
Claim Rejections - 35 USC § 103 – Andrews and NIH Clinical Trials as evidenced by Arai
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record) as applied to claims 1-2, 12, 16-18, 20, 22, 27, 31, 35, and 37, as evidenced by Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record). The following rejection is new and necessitated by Applicant’s amendments to the claims.
As stated above, the biodiffusion chamber of claim 18, and therefore, of claim 19, is interpreted as a product-by-process. Accordingly, the phrase “enriched for nestin expression before they are placed into the biodiffusion chamber” is interpreted as requiring that the tumor cells in the chamber express nestin.
The teachings of Andrews and NIH are described above and applied as to claims 2, 12, 16-18, 20, 22, 27, 31, 35, and 37 therein. Neither Andrews nor NIH teach that the tumor cells are enriched for nestin expression as interpreted above.
However, Arai examined the expression of nestin in brain tumors, and concluded that “glioblastomas constantly expressed nestin strongly” (pg. 166, left col.). Based on Arai, the glioblastoma tumor cells isolated from the subjects in Andrews’ method express nestin, and therefore, the biodiffusion chamber rendered obvious over Andrews and NIH meets the structural limitations of claim 19.
Response to Remarks - 35 USC § 103
Applicant’s remarks regarding the § 103 rejections raised in the prior action have been reviewed. Applicant’s remarks refer to the amendments to claim 1 as overcoming the rejections of record. As described above, Examiner agrees that the amendments to claim 1 are sufficient to overcome the § 102 rejections raised in the prior action over Andrews. These rejections have been withdrawn. However, as described above in paragraph 17, Andrews renders obvious the limitations of instant claim 1. Applicant’s remarks regarding the prior art rejections raised in the prior action do not address any other teachings or matters relevant to the § 103 rejections applied herein.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
U.S. Patent No. 6,541,036 B1
Claims 1-2, 12, 16-17, 27, 35, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 6,541,036 B1 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 1 recites “A method of inducing resistance to glioma tumor growth in a human comprising: (a) contacting a tumor cell in vitro or ex vivo with an oligonucleotide comprising SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:6; and (b) implanting a diffusion chamber containing said tumor cell into the rectus sheath of said human for a therapeutically effective time, thereby inducing resistance to glioma tumor growth.”
Like the instant claims, the patented method is directed to a method of treating cancer in which an IGF-1R AS ODN is administered to tumor cells ex vivo, the cells are then encapsulated in a biodiffusion chamber, and implanted into a subject with brain cancer. The teachings of Andrews are described above and applied as to instant claims 1-2, 12, 16-17, 27, 35, and 37 therein. Andrews teaches a substantially identical method to patented claim 1, in which the likelihood of the subject’s response to an IGF-1R AS ODN is evaluated by determining MGMT methylation or T cell function in the subject, e.g., by assessing IFN-γ in response to stimulation.
Regarding instant claims 1-2, 12, 35, and 37, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the patented method with steps of determining MGMT methylation or T cell function in the subject prior to administration of an IGF-1R AS ODN in view of Andrews, in order to arrive at the methods of the aforementioned claims. It would have amounted to a simple combination of known steps from two substantially identical methods, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in combining the steps because Andrews’ and the patented methods are substantially identical, and because Andrews teaches that it is well within the skilled artisan’s purview to assess T cell function and MGMT methylation in a subject. The skilled artisan would have been motivated to combine the steps because Andrews illustrates that the likelihood of a subject’s response to a substantially identical method comprising a biodiffusion chamber is correlated with the levels of MGMT methylation and T cell function, and the steps would, therefore, allow the skilled artisan to predict whether the patient would be a good candidate for the patented method.
Regarding instant claims 16-17, patented claim 4 recites that the tumor cell is selected from an “autograft.”
Regarding instant claim 27, patented SEQ ID NO: 2 is identical to instant SEQ ID NO: 1.
Claims 18, 20, 22, and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 6,541,036 B1 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
The teachings of Andrews and NIH are described above and applied as to claims 18, 20, 22, and 31 therein.
Regarding instant claims 18, 20, and 22, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the specific preparation steps taught by NIH to prepare the biodiffusion chamber in the patented method. It would have amounted to applying known steps to prepare a known element in a method (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the biodiffusion chamber as taught by NIH because NIH provides detailed instructions for preparing a substantially identical biodiffusion chamber to the chamber used in the patented method. The skilled artisan, seeking to prepare the biodiffusion chamber in order to practice the patented method, would have been motivated to utilize the specific preparation steps of NIH, because NIH provides detailed instructions, where the patented method is substantially more generic, and because NIH describes preparation of a biodiffusion chamber used in clinical trials, which is, therefore, likely to be relatively safe and effective in vivo.
Regarding instant claim 31, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implanted two or more biodiffusion chambers into the subject as taught by Andrews. It would have amounted to adapting the patented method to deliver more than one of a known element (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in implanting more than one biodiffusion chamber in the subject because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method of implanting ten biodiffusion chambers is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated to practice the patented method as taught by Andrews, because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 6,541,036 B1 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the tumor cell is selected from a “glioblastoma.” The teachings of Andrews and Pearson are described above and applied as to claim 14 described therein.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. It would have amounted to combining a patented method with a known treatment step, by known means to yield predictable results. Pearson teaches that temozolomide resistance can be overcome by IGF-1R inhibition. The patented method employs an IGF-1R inhibitor (i.e., the IGF-1R AS ODN), and Andrews illustrates improved outcomes in a cohort of subjects treated with substantially identical biodiffusion chambers comprising an IGF-1R inhibitor, owing in part to “better responses to temozolamide.” Accordingly, based on Andrews and Pearson, the skilled artisan would have had a reasonable expectation of success in adapting the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. Pearson strongly encourages exploration of new therapeutic approaches for glioblastoma. The skilled artisan would have recognized that the patented method employs an IGF-1R inhibitor with the potential to combat temozolomide resistance based on Pearson, and therefore, would have been motivated to adapt the patented method to illicit better responses to this “gold standard” glioblastoma treatment.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 6,541,036 B1 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record), NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record), and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the tumor cell is selected from a “glioblastoma.”
The teachings of Andrews, NIH, and Arai are described above and applied as to claim 19 described therein. Based on Arai, the glioblastoma tumor cell in the patented method expresses nestin, and therefore, the biodiffusion chamber of the patented method in view of Andrews and NIH meets the limitations of instant claim 19.
U.S. Patent No. 10,357,509 B2
Claims 1-2, 12, 16-18, 20, 22, 27, 31, 35, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,357,509 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 1 recites “A method of vaccinating a subject having a brain cancer comprising: (i) obtaining viable morselized tumor tissue from the subject; (ii) collecting the morselized tissue in a sterile trap; (iii) harvesting adherent cells from the morselized tissue; (iv) encapsulating the harvested cells in a biodiffusion chamber along with insulin-like growth factor receptor-1 antisense oligodeoxynucleotide (IGF-1R AS ODN) having the sequence of SEQ ID NO:1; wherein the chamber contains about 1×104 to about 5×106 tumor cells and about 1 μg to about 5 μg of the IGF-1R AS ODN; (v) irradiating the chamber, and (vi) implanting the chamber in the subject, wherein an immune response against the brain cancer is obtained.”
Like the instant claims, the patented method is directed to a method of treating cancer, in which an IGF-1R AS ODN is administered to tumor cells isolated from a subject with brain cancer, the cells are then encapsulated in a biodiffusion chamber, which is then implanted into the subject. The teachings of Andrews are described above and applied as to instant claims 1-2, 12, 16-18, 20, 22, 27, 31, 35, and 37 therein. Andrews teaches a substantially identical method to patented claim 1, in which the likelihood of the subject’s response to an IGF-1R AS ODN is evaluated by determining MGMT methylation or T cell function in the subject, e.g., by assessing IFN-γ in response to stimulation.
Regarding instant claims 1-2, 12, 16-18, 20, and 35, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention t to have combined the patented method with steps of determining MGMT methylation or T cell function in the subject prior to administration of an IGF-1R AS ODN in view of Andrews, in order to arrive at the methods of the aforementioned claims. It would have amounted to a simple combination of known steps from two substantially identical methods, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in combining the steps because Andrews’ and the patented methods are substantially identical, and because Andrews teaches that it is well within the skilled artisan’s purview to assess T cell function and MGMT methylation in a subject. The skilled artisan would have been motivated to combine the steps because Andrews illustrates that the likelihood of response to a substantially identical method comprising a biodiffusion chamber is correlated with the levels of MGMT methylation and T cell function, and the steps would, therefore, allow the skilled artisan to predict whether the patient would be a good candidate for the patented method.
Patented claim 2 meets the limitations of instant claim 22.
Regarding instant claim 27, patented SEQ ID NO: 1 is identical to instant SEQ ID NO: 1.
Patented claim 3 meets the limitations of instant claim 31.
Regarding instant claim 37, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have practiced the patented method in human subjects as taught by Andrews. It would have amounted to substituting a generic subject for a human subject, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in practicing the patented method in human subjects because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated to practice the patented method in human subjects because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of U.S. Patent No. 10,357,509 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 8 recites that the brain cancer is “a grade IV astrocytoma (glioblastoma multiforme).” The teachings of Andrews and Pearson are described above and applied as to claim 14 described therein.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. It would have amounted to combining a patented method with a known treatment step, by known means to yield predictable results. Pearson teaches that temozolomide resistance can be overcome by IGF-1R inhibition. The patented method employs an IGF-1R inhibitor (i.e., the IGF-1R AS ODN), and Andrews illustrates improved outcomes in a cohort of subjects treated with substantially identical biodiffusion chambers comprising an IGF-1R inhibitor, owing in part to “better responses to temozolamide.” Accordingly, based on Andrews and Pearson, the skilled artisan would have had a reasonable expectation of success in adapting the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. Pearson strongly encourages exploration of new therapeutic approaches for glioblastoma. The skilled artisan would have recognized that the patented method employs an IGF-1R inhibitor with the potential to combat temozolomide resistance based on Pearson, and therefore, would have been motivated to adapt the patented method to illicit better responses to this “gold standard” glioblastoma treatment.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of U.S. Patent No. 10,357,509 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 8 recites that the brain cancer is “a grade IV astrocytoma (glioblastoma multiforme).”
The teachings of Andrews and Arai are described above and applied as to claim 19 described therein. As stated therein, based on Arai, the glioblastoma tumor tissue isolated from the subject in the patented method expresses nestin, and therefore, the biodiffusion chamber of the patented method in view of Andrews meets the limitations of instant claim 19.
U.S. Patent No. 10,772,904 B2
Claims 1-2, 12, 16-17, 27, 35, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,772,904 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 1 recites “A method of vaccinating a subject having a brain cancer comprising:
(i) obtaining viable morselized tumor tissue from the subject; (ii) collecting the morselized tissue in a sterile trap; (iii) harvesting adherent cells from the morselized tissue; (iv) encapsulating the harvested cells in a biodiffusion chamber along with insulin-like growth factor receptor-1 antisense oligodeoxynucleotide (IGF-1R AS ODN) having the sequence of SEQ ID NO:1; (v) irradiating the chamber, and (vi) implanting the chamber in the subject, wherein an immune response against the brain cancer is obtained.”
Like the instant claims, the patented method is directed to a method of treating cancer, in which an IGF-1R AS ODN is administered to tumor cells isolated from a subject with brain cancer, the cells are then encapsulated in a biodiffusion chamber, which is then implanted into the subject. The teachings of Andrews are described above and applied as to instant claims 1-2, 12, 16-17, 27, 35, and 37 therein. Andrews teaches a substantially identical method to patented claim 1, in which the likelihood of the subject’s response to an IGF-1R AS ODN is evaluated by determining MGMT methylation or T cell function in the subject, e.g., by assessing IFN-γ in response to stimulation.
Regarding instant claims 1-2, 12, 16-17, and 35, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the patented method with steps of determining MGMT methylation or T cell function in the subject prior to administration of an IGF-1R AS ODN in view of Andrews, in order to arrive at the methods of the aforementioned claims. It would have amounted to a simple combination of known steps from two substantially identical methods, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in combining the steps because Andrews’ and the patented methods are substantially identical, and because Andrews teaches that it is well within the skilled artisan’s purview to assess T cell function and MGMT methylation in a subject. The skilled artisan would have been motivated to combine the steps because Andrews illustrates that the likelihood of a subject’s response to a substantially identical method comprising a biodiffusion chamber is correlated with the levels of MGMT methylation and T cell function, and the steps would, therefore, allow the skilled artisan to predict whether the patient would be a good candidate for the patented method.
Regarding instant claim 27, patented SEQ ID NO: 1 is identical to instant SEQ ID NO: 1.
Regarding instant claim 37, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have practiced the patented method in human subjects as taught by Andrews. It would have amounted to substituting a generic subject for a human subject, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in practicing the patented method in human subjects because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated to practice the patented method in human subjects because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claims 18, 20, 22, and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,772,904 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claims 4-7 recite tumor cell numbers and amounts of IGF-1R AS ODN which meet the instant limitations, but they are not recited in the same claim such that a ratio meeting the instant limitations is encompassed.
The teachings of Andrews and NIH are described above and applied as to claims 18, 20, 22, and 31 therein.
Regarding instant claims 18 and 20, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the specific preparation steps taught by NIH to prepare the biodiffusion chamber in the patented method. It would have amounted to applying known steps to prepare a known element in a method (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the biodiffusion chamber as taught by NIH because NIH provides detailed instructions for preparing a substantially identical biodiffusion chamber to the chamber used in the patented method. The skilled artisan, seeking to prepare the biodiffusion chamber in order to practice the patented method, would have been motivated to utilize the specific preparation steps of NIH, because NIH provides detailed instructions, where the patented method is substantially more generic, and because NIH describes preparation of a biodiffusion chamber used in clinical trials, which is, therefore, likely to be relatively safe and effective in vivo.
Patented claim 2 meets the limitations of instant claim 22.
Patented claim 3 meets the limitations of instant claim 31.
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 10,772,904 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 10 recites that the brain cancer is “a grade IV astrocytoma (glioblastoma multiforme).” The teachings of Andrews and Pearson are described above and applied as to claim 14 described therein.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. It would have amounted to combining a patented method with a known treatment step, by known means to yield predictable results. Pearson teaches that temozolomide resistance can be overcome by IGF-1R inhibition. The patented method employs an IGF-1R inhibitor (i.e., the IGF-1R AS ODN), and Andrews illustrates improved outcomes in a cohort of subjects treated with substantially identical biodiffusion chambers comprising an IGF-1R inhibitor, owing in part to “better responses to temozolamide.” Accordingly, based on Andrews and Pearson, the skilled artisan would have had a reasonable expectation of success in adapting the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. Pearson strongly encourages exploration of new therapeutic approaches for glioblastoma. The skilled artisan would have recognized that the patented method employs an IGF-1R inhibitor with the potential to combat temozolomide resistance based on Pearson, and therefore, would have been motivated to adapt the patented method to illicit better responses to this “gold standard” glioblastoma treatment.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 10,772,904 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record), NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record), and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 10 recites that the brain cancer is “a grade IV astrocytoma (glioblastoma multiforme).”
The teachings of Andrews, NIH, and Arai are described above and applied as to claim 19 described therein. Based on Arai, the glioblastoma tumor tissue isolated from the subject in the patented method expresses nestin, and therefore, the biodiffusion chamber of the patented method in view of Andrews and NIH meets the limitations of instant claim 19.
U.S. Patent No. 10,543,226 B2
Claims 1-2, 12, 16-17, 27, 35, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-23 of U.S. Patent No. 10,543,226 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 11 recites “A method for inducing an anti-tumor immune response in a subject in need thereof, the method comprising implanting a diffusion chamber into the subject for a therapeutically effective time, wherein the diffusion chamber is prepared by: a) treating tumor cells from the subject ex vivo with a first amount of an IGF-1R AS ODN; b) washing the tumor cells to remove the first amount of the IGF-1R AS ODN; c) placing the tumor cells and a second amount of the IGF-1R AS ODN in the diffusion chamber; and d) irradiating the tumor cells and the second amount of the IGF-1R AS ODN in the diffusion chamber; wherein the IGF-1R AS ODN has the sequence of SEQ ID NO: 1; and wherein the tumor cells are from a patient suffering from glioma, astrocytoma, breast cancer, head and neck squamous cell cancer, papillary renal cell carcinoma Type II, lung cancer, pancreatic cancer, gall bladder cancer, rectal cancer, classical Hodgkin's lymphoma, ovarian cancer, or colorectal cancer.
Like the instant claims, the patented method is directed to a method of treating cancer, in which an IGF-1R AS ODN is administered to tumor cells isolated from a subject, e.g., a subject with brain cancer, the cells are then encapsulated in a biodiffusion chamber, which is then implanted into the subject. The teachings of Andrews are described above and applied as to instant claims 1-2, 12, 16-17, 27, 35, and 37 therein. Andrews teaches a substantially identical method to patented claim 11, in which the likelihood of the subject’s response to an IGF-1R AS ODN is evaluated by determining MGMT methylation or T cell function in the subject, e.g., by assessing IFN-γ in response to stimulation.
Regarding instant claims 1-2, 12, 16-17, and 35, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the patented method with steps of determining MGMT methylation or T cell function in the subject prior to administration of an IGF-1R AS ODN in view of Andrews, in order to arrive at the methods of the aforementioned claims. It would have amounted to a simple combination of known steps from two substantially identical methods, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in combining the steps because Andrews’ and the patented methods are substantially identical, and because Andrews teaches that it is well within the skilled artisan’s purview to assess T cell function and MGMT methylation in a subject. The skilled artisan would have been motivated to combine the steps because Andrews illustrates that the likelihood of subject’s response to a substantially identical method comprising a biodiffusion chamber is correlated with the levels of MGMT methylation and T cell function, and the steps would, therefore, allow the skilled artisan to predict whether the patient would be a good candidate for the patented method.
Regarding instant claim 27, patented SEQ ID NO: 1 is identical to instant SEQ ID NO: 1.
Regarding instant claim 37, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have practiced the patented method in human subjects as taught by Andrews. It would have amounted to substituting a generic subject for a human subject, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in practicing the patented method in human subjects because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated to practice the patented method in human subjects because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claims 18, 20, 22, and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-23 of U.S. Patent No. 10,543,226 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
The teachings of Andrews and NIH are described above and applied as to claims 18, 20, 22, and 31 therein.
Regarding instant claims 18, 20, and 22, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the specific preparation steps taught by NIH to prepare the biodiffusion chamber in the patented method. It would have amounted to applying known steps to prepare a known element in a method (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the biodiffusion chamber as taught by NIH because NIH provides detailed instructions for preparing a substantially identical biodiffusion chamber to the chamber used in the patented method. The skilled artisan, seeking to prepare the biodiffusion chamber in order to practice the patented method, would have been motivated to utilize the specific preparation steps of NIH, because NIH provides detailed instructions, where the patented method is substantially more generic, and because NIH describes preparation of a biodiffusion chamber used in clinical trials, which is, therefore, likely to be relatively safe and effective in vivo.
Regarding instant claim 31, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implanted two or more biodiffusion chambers into the subject as taught by Andrews. It would have amounted to adapting the patented method to deliver more than one of a known element (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in implanting more than one biodiffusion chamber in the subject because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method of implanting ten biodiffusion chambers is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated practice the patented method as taught by Andrews, because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-23 of U.S. Patent No. 10,543,226 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the tumor cells are from a subject suffering from “glioma.” The teachings of Andrews and Pearson are described above and applied as to claim 14 described therein.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. It would have amounted to combining a patented method with a known treatment step, by known means to yield predictable results. Pearson teaches that temozolomide resistance can be overcome by IGF-1R inhibition. The patented method employs an IGF-1R inhibitor (i.e., the IGF-1R AS ODN), and Andrews illustrates improved outcomes in a cohort of subjects treated with substantially identical biodiffusion chambers comprising an IGF-1R inhibitor, owing in part to “better responses to temozolamide.” Accordingly, based on Andrews and Pearson, the skilled artisan would have had a reasonable expectation of success in adapting the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. Pearson strongly encourages exploration of new therapeutic approaches for glioblastoma. The skilled artisan would have recognized that the patented method employs an IGF-1R inhibitor with the potential to combat temozolomide resistance based on Pearson, and therefore, would have been motivated to adapt the patented method to illicit better responses to this “gold standard” glioblastoma treatment.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-23 of U.S. Patent No. 10,543,226 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record), NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record), and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the tumor cells are from a subject suffering from “glioma.”
The teachings of Andrews, NIH, and Arai are described above and applied as to claim 19 described therein. As stated therein, based on Arai, glioma tissue expresses nestin, and therefore, the biodiffusion chamber of the patented method in view of Andrews and NIH meets the limitations of instant claim 19.
U.S. Patent No. 10,265,339 B2
Claims 1-2, 12, 16-17, 27, 35, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-24 of U.S. Patent No. 10,265,339 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 11 recites “A method for inducing an anti-tumor immune response in a subject in need thereof, the method comprising implanting a diffusion chamber into the subject for a therapeutically effective time, wherein the diffusion chamber is prepared by: a) treating tumor cells from the subject ex vivo with a first amount of an IGF-1R AS ODN, wherein the IGF-IR AS ODN has the sequence of SEQ ID NO: 1; b) washing the tumor cells to remove the first amount of the IGF-1R AS ODN; c) placing the tumor cells and a second amount of the IGF-1R AS ODN in the diffusion chamber; and d) irradiating the tumor cells and the second amount of the IGF-1R AS ODN in the diffusion chamber.”
Like the instant claims, the patented method is directed to a method of treating cancer, in which an IGF-1R AS ODN is administered to tumor cells isolated from a subject, the cells are then encapsulated in a biodiffusion chamber, which is then implanted into the subject. The teachings of Andrews are described above and applied as to instant claims 1-2, 12, 16-17, 27, 35, and 37 therein. Andrews teaches a substantially identical method to patented claim 11, in which the likelihood of the subject’s response to an IGF-1R AS ODN is evaluated by determining MGMT methylation or T cell function in the subject, e.g., by assessing IFN-γ in response to stimulation.
Regarding instant claims 1-2, 12, 16-17, and 35, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the patented method with steps of determining MGMT methylation or T cell function in the subject prior to administration of an IGF-1R AS ODN in view of Andrews, in order to arrive at the methods of the aforementioned claims. It would have amounted to a simple combination of known steps from two substantially identical methods, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in combining the steps because Andrews’ and the patented methods are substantially identical, and because Andrews teaches that it is well within the skilled artisan’s purview to assess T cell function and MGMT methylation in a subject. The skilled artisan would have been motivated to combine the steps because Andrews illustrates that the likelihood of a subject’s response to a substantially identical method comprising a biodiffusion chamber is correlated with the levels of MGMT methylation and T cell function, and the steps would, therefore, allow the skilled artisan to predict whether the patient would be a good candidate for the patented method.
Regarding instant claim 27, patented SEQ ID NO: 1 is identical to instant SEQ ID NO: 1.
Regarding instant claim 37, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have practiced the patented method in human subjects as taught by Andrews. It would have amounted to substituting a generic subject for a human subject, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in practicing the patented method in human subjects because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated to practice the patented method in human subjects because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claims 18, 20, 22, and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-24 of U.S. Patent No. 10,265,339 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
The teachings of Andrews and NIH are described above and applied as to claims 18, 20, 22, and 31 therein.
Regarding instant claims 18, 20, and 22, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the specific preparation steps taught by NIH to prepare the biodiffusion chamber in the patented method. It would have amounted to applying known steps to prepare a known element in a method (i.e., a biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the biodiffusion chamber as taught by NIH because NIH provides detailed instructions for preparing a substantially identical biodiffusion chamber to the chamber used in the patented method. The skilled artisan seeking to prepare the biodiffusion chamber in order to practice the patented method, would have been motivated to utilize the specific preparation steps of NIH, because NIH provides detailed instructions, where the patented method is substantially more generic, and because NIH describes preparation of a biodiffusion chamber used in clinical trials, which is, therefore, likely to be relatively safe and effective in vivo.
Regarding instant claim 31, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implanted two or more biodiffusion chambers into the subject as taught by Andrews. It would have amounted to adapting the patented method to deliver more than one of a known element (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in implanting more than one biodiffusion chamber in the subject because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method of implanting ten biodiffusion chambers is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated practice the patented method as taught by Andrews, because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-24 of U.S. Patent No. 10,265,339 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the subject is suffering from “glioma.” The teachings of Andrews and Pearson are described above and applied as to claim 14 described therein.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. It would have amounted to combining a patented method with a known treatment step, by known means to yield predictable results. Pearson teaches that temozolomide resistance can be overcome by IGF-1R inhibition. The patented method employs an IGF-1R inhibitor (i.e., the IGF-1R AS ODN), and Andrews illustrates improved outcomes in a cohort of subjects treated with substantially identical biodiffusion chambers comprising an IGF-1R inhibitor, owing in part to “better responses to temozolamide.” Accordingly, based on Andrews and Pearson, the skilled artisan would have had a reasonable expectation of success in adapting the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. Pearson strongly encourages exploration of new therapeutic approaches for glioblastoma. The skilled artisan would have recognized that the patented method employs an IGF-1R inhibitor with the potential to combat temozolomide resistance based on Pearson, and therefore, would have been motivated to adapt the patented method to illicit better responses to this “gold standard” glioblastoma treatment.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-24 of U.S. Patent No. 10,265,339 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record), NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record), and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the subject is suffering from “glioma.”
The teachings of Andrews, NIH, and Arai are described above and applied as to claim 19 described therein. Based on Arai, glioma tissue expresses nestin, and therefore, the biodiffusion chamber of the patented method in view of Andrews and NIH meets the limitations of instant claim 19.
U.S. Patent No. 11,077,133 B2
Claims 1-2, 12, 16-17, 27, 35, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,077,133 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 1 recites “A method for treating cancer in a subject in need thereof, the method comprising: systemically administering to the subject an effective amount of a pharmaceutical composition comprising a first Insulin-like Growth Factor-1 Receptor antisense oligonucleotide (IGF-1R AS ODN), wherein the sequence of the first IGF-1R AS ODN is SEQ ID NO: 1, and wherein the first IGF-1R AS ODN has a modified phosphate backbone; and administering to the subject at least one biodiffusion chamber, the chamber comprising tumor cells and a second IGF-1R AS ODN, wherein the sequence of the second IGF-1R AS ODN is SEQ ID NO:1, and wherein the second IGF-1R AS ODN has a modified phosphate backbone.”
Like the instant claims, the patented method is directed to a method of treating cancer, in which an IGF-1R AS ODN and tumor cells are encapsulated in a biodiffusion chamber, which is then administered to a subject having cancer. The teachings of Andrews are described above and applied as to instant claims 1-2, 12, 16-17, 27, 35, and 37 therein. Andrews teaches a substantially identical method to patented claim 1, in which the likelihood of the subject’s response to an IGF-1R AS ODN is evaluated by determining MGMT methylation or T cell function in the subject, e.g., by assessing IFN-γ in response to stimulation.
Regarding instant claims 1-2, 12, 16-17, and 35, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the patented method with steps of determining MGMT methylation or T cell function in the subject prior to administration of an IGF-1R AS ODN in view of Andrews, in order to arrive at the methods of the aforementioned claims. It would have amounted to a simple combination of known steps from two substantially identical methods, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in combining the steps because Andrews’ and the patented methods are substantially identical, and because Andrews teaches that it is well within the skilled artisan’s purview to assess T cell function and MGMT methylation in a subject. The skilled artisan would have been motivated to combine the steps because Andrews illustrates that the likelihood of a subject’s response to a substantially identical method comprising a biodiffusion chamber is correlated with the levels of MGMT methylation and T cell function, and the steps would, therefore, allow the skilled artisan to predict whether the patient would be a good candidate for the patented method.
Regarding instant claim 27, patented SEQ ID NO: 1 is identical to instant SEQ ID NO: 1.
Regarding instant claim 37, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have practiced the patented method in human subjects as taught by Andrews. It would have amounted to substituting a generic subject for a human subject, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in practicing the patented method in human subjects because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated to practice the patented method in human subjects because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claims 18, 20, 22, and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,077,133 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
The teachings of Andrews and NIH are described above and applied as to claims 18, 20, 22, and 31 therein.
Regarding instant claims 18, 20, and 22, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the specific preparation steps taught by NIH to prepare the biodiffusion chamber in the patented method. It would have amounted to applying known steps to prepare a known element in a method (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the biodiffusion chamber as taught by NIH because NIH provides detailed instructions for preparing a substantially identical biodiffusion chamber to the chamber used in the patented method. The skilled artisan seeking to prepare the biodiffusion chamber in order to practice the patented method, would have been motivated to utilize the specific preparation steps of NIH, because NIH provides detailed instructions, where the patented method is substantially more generic, and because NIH describes preparation of a biodiffusion chamber used in clinical trials, which is, therefore, likely to be relatively safe and effective in vivo.
Regarding instant claim 31, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implanted two or more biodiffusion chambers into the subject as taught by Andrews. It would have amounted to adapting the patented method to deliver more than one of a known element (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in implanting more than one biodiffusion chamber in the subject because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method of implanting ten biodiffusion chambers is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated practice the patented method as taught by Andrews, because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,077,133 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the cancer is “glioma.” The teachings of Andrews and Pearson are described above and applied as to claim 14 described therein.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. It would have amounted to combining a patented method with a known treatment step, by known means to yield predictable results. Pearson teaches that temozolomide resistance can be overcome by IGF-1R inhibition. The patented method employs an IGF-1R inhibitor (i.e., the IGF-1R AS ODN), and Andrews illustrates improved outcomes in a cohort of subjects treated with substantially identical biodiffusion chambers comprising an IGF-1R inhibitor, owing in part to “better responses to temozolamide.” Accordingly, based on Andrews and Pearson, the skilled artisan would have had a reasonable expectation of success in adapting the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. Pearson strongly encourages exploration of new therapeutic approaches for glioblastoma. The skilled artisan would have recognized that the patented method employs an IGF-1R inhibitor with the potential to combat temozolomide resistance based on Pearson, and therefore, would have been motivated to adapt the patented method to illicit better responses to this “gold standard” glioblastoma treatment.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,077,133 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record), NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record), and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the cancer is “glioma.”
The teachings of Andrews, NIH, and Arai are described above and applied as to claim 19 described therein. Based on Arai, glioma tissue expresses nestin, and therefore, the biodiffusion chamber of the patented method in view of Andrews and NIH meets the limitations of instant claim 19.
U.S. Patent No. 12,064,446 B2
Claims 1-2, 12, 16-17, 27, 35, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-6 of U.S. Patent No. 12,064,446 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Patented claim 2 recites “ A method for inducing an anti-tumor immune response in a subject in need thereof, the method comprising implanting an immunogenic diffusion chamber into the subject for a therapeutically effective time, wherein the immunogenic diffusion chamber comprises an Insulin-like Growth Factor-1 Receptor antisense oligodeoxynucleotide (IGF-1R AS ODN), wherein the IGF-1R AS ODN has the sequence of SEQ ID NO: 1,” “wherein the immunogenic diffusion chamber further comprises tumor cells and a second amount of the IGF-1R AS ODN, wherein the tumor cells and the second amount of the IGF-1R AS ODN are irradiated with gamma radiation.”
Like the instant claims, the patented method is directed to a method of treating cancer, in which an IGF-1R AS ODN and tumor cells are encapsulated in a biodiffusion chamber, irradiated, and administered to a subject having cancer. The teachings of Andrews are described above and applied as to instant claims 1-2, 12, 16-17, 27, 35, and 37 therein. Andrews teaches a substantially identical method to patented claim 2, in which the likelihood of the subject’s response to an IGF-1R AS ODN is evaluated by determining MGMT methylation or T cell function in the subject, e.g., by assessing IFN-γ in response to stimulation.
Regarding instant claims 1-2, 12, 16-17, and 35, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the patented method with steps of determining MGMT methylation or T cell function in a subject with brain cancer (i.e., glioblastoma) prior to administration of an IGF-1R AS ODN in view of Andrews, in order to arrive at the methods of the aforementioned claims. It would have amounted to a simple combination of known steps from two substantially identical methods, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in combining the steps because Andrews’ and the patented methods are substantially identical, and because Andrews teaches that it is well within the skilled artisan’s purview to assess T cell function and MGMT methylation in a subject with brain cancer. The skilled artisan would have been motivated to combine the steps because Andrews illustrates that the likelihood of a subject’s response to a substantially identical method comprising a biodiffusion chamber is correlated with the levels of MGMT methylation and T cell function, and the steps would, therefore, allow the skilled artisan to predict whether a patient would be a good candidate for the patented method.
Regarding instant claim 27, patented SEQ ID NO: 1 is identical to instant SEQ ID NO: 1.
Regarding instant claim 37, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have practiced the patented method in human subjects as taught by Andrews. It would have amounted to substituting a generic subject for a human subject, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in practicing the patented method in human subjects because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated to practice the patented method in human subjects because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claims 18, 20, 22, and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-6 of U.S. Patent No. 12,064,446 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record). The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
The teachings of Andrews and NIH are described above and applied as to claims 18, 20, 22, and 31 therein.
Regarding instant claims 18, 20, and 22, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the specific preparation steps taught by NIH to prepare the biodiffusion chamber in the patented method. It would have amounted to applying known steps to prepare a known element in a method (i.e., a biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the biodiffusion chamber as taught by NIH because NIH provides detailed instructions for preparing a substantially identical biodiffusion chamber to the chamber used in the patented method. The skilled artisan seeking to prepare the biodiffusion chamber in order to practice the patented method, would have been motivated to utilize the specific preparation steps of NIH, because NIH provides detailed instructions, where the patented method is substantially more generic, and because NIH describes preparation of a biodiffusion chamber used in clinical trials, which is, therefore, likely to be relatively safe and effective in vivo.
Regarding instant claim 31, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implanted two or more biodiffusion chambers into the subject as taught by Andrews. It would have amounted to adapting the patented method to deliver more than one of a known element (i.e., the biodiffusion chamber), by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in implanting more than one biodiffusion chamber in the subject because Andrews’ and the patented methods are substantially identical, and because Andrews demonstrates that their method of implanting ten biodiffusion chambers is “well-tolerated with a favorable median survival” in human subjects (see “Conclusions,” pg. 7). The skilled artisan would have been motivated to practice the patented method as taught by Andrews, because Andrews teaches their data “support [] a novel treatment paradigm that promotes anti-tumor immunity” in human subjects with glioblastoma (see “Conclusions,” pg. 7).
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-6 of U.S. Patent No. 12,064,446 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record) and Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the subject is suffering from “glioma.” The teachings of Andrews and Pearson are described above and applied as to claim 14 described therein.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. It would have amounted to combining a patented method with a known treatment step, by known means to yield predictable results. Pearson teaches that temozolomide resistance can be overcome by IGF-1R inhibition. The patented method employs an IGF-1R inhibitor (i.e., the IGF-1R AS ODN), and Andrews illustrates improved outcomes in a cohort of subjects treated with substantially identical biodiffusion chambers comprising an IGF-1R inhibitor, owing in part to “better responses to temozolamide.” Accordingly, based on Andrews and Pearson, the skilled artisan would have had a reasonable expectation of success in adapting the patented method to administer the IGF-1R AS ODN-comprising biodiffusion chamber prior to administering temozolomide. Pearson strongly encourages exploration of new therapeutic approaches for glioblastoma. The skilled artisan would have recognized that the patented method employs an IGF-1R inhibitor with the potential to combat temozolomide resistance based on Pearson, and therefore, would have been motivated to adapt the patented method to illicit better responses to this “gold standard” glioblastoma treatment.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-6 of U.S. Patent No. 12,064,446 B2 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record), NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record), and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record). The following rejection is maintained and modified as necessitated by Applicant’s amendments to the claims.
The patented claims recite that the subject is suffering from “glioma.”
The teachings of Andrews, NIH, and Arai are described above and applied as to claim 19 described therein. Based on Arai, glioma tissue expresses nestin, and therefore, the biodiffusion chamber of the patented method in view of Andrews and NIH meets the limitations of instant claim 19.
Co-pending Application Nos. 18/471,355 and 18/742,486
Claims 1-2, 12, 14, 16-20, 22, 27, 31, 35, and 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of Application No. 18/471,355 in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record), NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record), Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record), and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record) as applied in the preceding paragraphs. The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
Claims 1-2, 12, 14, 16-20, 22, 27, 31, 35, and 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-16, 18, 20, and 26-29 of Application No. 18/742,486, in view of Andrews (Andrews et al., 28 February 2018, JHN Journal, doi.org/10.29046/JHNJ.013.1.002, Vol. 13, Issue 1, pg. 6-13; of record), NIH Clinical Trials (“Pilot Immunotherapy Trial for Recurrent Malignant Gliomas,” ID: NCT01550523, Record submitted 2 December 2013, accessed 18 August 2025; of record), Pearson (Pearson and Regad, 29 September 2017, Signal Transduction and Targeted Therapy, 2, e17040, pg. 1-11; of record), and Arai (Arai et al., 2012, Brain Tumor Pathol, 29, pg. 160-167; of record) as applied in the preceding paragraphs. The following rejections are maintained and modified as necessitated by Applicant’s amendments to the claims.
The aforementioned claims of the co-pending Applications are directed to substantially identical methods to the instant claims, comprising vaccinating a subject, e.g., a subject having brain cancer, with an irradiated biodiffusion chamber comprising tumor cells isolated from the subject and an IGF-1R AS ODN. For the reasons described above as for the patented claims, the instant claims are also obvious over the co-pending claims in Application Nos. 18/471,355 and 18/742,486 in view of Andrews, NIH, Pearson, and/or Arai.
These rejections are provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented.
Response to Remarks – Nonstatutory Double Patenting
Examiner acknowledges Applicant’s request that the rejections be held in abeyance until claims are deemed allowable in the instant application. The previous rejections are maintained and modified herein, because Applicant’s amendments to the claims are not sufficient to distinguish the instant claims from the patented and co-pending claims for the reasons described above, and no terminal disclaimers have been filed.
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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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
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