DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 18-19, 21, 25-27, 29 and 33-35 are under consideration.
Rejections Maintained
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 18-19, 21, 25-27, 29 and 33-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Andrews (Andrews, et al., WO 00/09145; Published 02/24/2000, of record) in view of Han (Han, et al., J. Exper. & Clin. Cancer Res (2017) 36:156, of record) and Zhang (Zhang, et al., World J Gastroenterology 2006 12(25):3977, of record)
Andrews teaches on the subject of methods of inducing regression of a tumor comprising treating a tumor cell ex vivo with a pro-apoptotic agent, placing the treated tumor cells in a diffusion chamber and inserting the chamber into a human for a therapeutically effective amount of time (Andrews, Abstract). Andrews teaches that the method of Andrews is capable of treating cancer using any tumor cells that undergo apoptosis and induce resistance or regression of tumor cells (Andres, p 6, lines 1-6). Andrews teaches that the pro-apoptotic agent of Andrews is a nucleic acid molecule directed against IGF-IR having the sequence of Andrews’ SEQ ID NO: 9 (same as instant SEQ ID NO: 1) (Andrews, p 7, line 20 – p 8, line 13). Regarding the “two or more” chambers limitation of claims 18 and 29 as well as the 10 to 30 chambers limitation of claim 19 and the 20 chambers limitation of claim 34, Andrews teaches that between five and 20 chambers are implanted in a single patient and the chambers can be removed after 24-30 hours after implantation, if desired (Andrews, p 12, lines 23-30). Regarding limitations i-ii of claim 29, Andrews teaches that the tumor sample is disaggregated with a scalpel, treated with collagenase/protease and then plated and allowed to attach 4-6 hr before washing (Andrews, p 17, lines 16-22), with the chopping with the scalpel converting the tissue into “morselized” tissue and the “sterile trap” being the sterile container the morselized tissue is in and the plating/attachment/ steps satisfying “harvesting adherent cells”. Regarding claim 33 as well as the irradiation limitations of claims 1 and 29, Andrews teaches that the adherent cells are then treated with IGF-IR antisense oligonucleotide for 6-10 hours, placed in a diffusion chamber and irradiated with 6 Gy prior to implantation (Andrews, p 17, line 22- p 18, line 8). Regarding claims 25 and 35, p 14, line 1 through p 26, line 18 of the Andrews reference teaches a detailed protocol used in a clinical trial for the method of Andrews and none of the steps described would expose the tumor cells to temperatures over body temperatures and no chemotherapy or radiation was used on the patients. Regarding claims 26-27, Andrews teaches that three patients who failed initial treatment were re-treated with a higher biological dose under FDA compassionate use (Andrews, p 24, lines 6-10) and while Andrews does not teach whether the cells were obtained after the first harvest or not, this does not matter as it has to be one or the other and claim 27 a) does not require non-response or recurrence.
Additionally, Andrews teaches that situations wherein the pretreated tumor cells undergo apoptosis in the diffusion chambers prior to implantation, the time between when the tumor cells are harvested from the plates until implantation should be an hour maximum, with preference being this time being as small as possible (Andrews, p 18, lines 10-21).
Andrews does not teach that the cancer being treated is hepatocellular cancer (HCC). Andrews does not teach that the chambers are implanted for 48 hours. Andrews does not teach that the tumor cells are encapsulated in the diffusion chamber with IGF-IR antisense.
Han teaches on the subject of whole cell tumor vaccines for HCC comprising HCC cells and a STAT3 decoy oligonucleotide (Han, Abstract- Background and Methods). Han teaches that whole cell vaccines often fail to demonstrate clinical benefit, with poor immunogenicity and immune tolerance/immunosuppression in the stromal microenvironment being possible explanations (Han, p 2, ¶ 2). Han teaches that STAT3 is overexpressed in many tumors and that previous findings confirmed blocking STAT3 signaling in HCC cells inhibited proliferation, promoted apoptosis and were sensitized to killing by NK cells, leading to the hypothesis that STAT3-blocked HCC cells could be used as a vaccine (Han, p 2, ¶ 3). Han teaches that vaccination with the decoy ODN yielded significantly smaller tumor volumes in BALB/c and C57BL/6 mice and longer survival times compared to scrambled ODN, lipofectamine or PBS (Han, Fig. 1).
Zhang teaches on the subject of IGF-IR inhibition in HCC (Zhang, Abstract). Zhang teaches that downregulation of IGF-IR function by antisense and dominant negative techniques reduces the growth and tumorigenicity of several cancer cell lines, thus rendering IGF-IR an attractive therapeutic target based on the hypothesis that inhibition would result in apoptosis and growth inhibition in tumor cells (Zhang, p 3978, ¶ 1). Zhang teaches that HepG2 HCC cells and Chang normal liver cells were treated with the IGF-IR inhibiting antibody aIR3 (Zhang, p 3978, ¶ 1-3). Zhang teaches that aIR3 both decreased cell growth (Zhang, Table 1) and increased apoptotic index (Zhang, Table 2) of the HepG2 HCC cells, both in dose-dependent manners.
It would be prima facie obvious to one of ordinary skill in the art to apply the biodiffusion method of Andrews to HCC in view of the teachings of Han and Zhang to arrive at a method of treating HCC comprising autologous HCC cells that have been transfected with the STAT3 decoy ODN of Han encapsulated in two or more of the biodiffusion chambers of Andrews with IGF-IR antisense in the biodiffusion chamber as well. One of ordinary skill in the art would be motivated to do this in order to better fight HCC. Andrews teaches that the biodiffusion chamber method of Andrews can be used to treat any form of cancer so long as the cells associated with that cancer undergo apoptosis and the resultant cells are capable of inducing an immune response. The teachings of Zhang demonstrate that inhibition of IGF-IR leads to apoptosis in HCC cells and the teachings of Han demonstrate that apoptotic HCC cells can create an anti-tumor response, and this creates a reasonable expectation of success with respect to the use of HCC cells in the biodiffusion chamber method of Andrews.
Andrews also teaches that is preferred to have the cells undergo apoptosis after the biodiffusion chamber has been implanted and this creates a time limit between when the tumor cells are harvested from the IGF-IR antisense treatment plate until implantation of one hour, with less time being better. This creates motivation to put IGF-IR antisense in the chamber with the cells, which one of ordinary skill in the art would reasonably assume would bypass this rush period and guarantee the cells undergo apoptosis in the patient with a reasonable expectation of success.
Regarding the 48-hour implantation limitation, Andrews teaches that the diffusion chambers of Andrews may be removed after 30 hours, if desired (Andrews, p 12, lines 23-30). This renders leaving the chambers in longer and reaching the 48-hour mark as obvious, as removing the chambers after 30 hours is optional. This leaves one of skill in the art the freedom to leave the chambers in longer than 30 hours in an attempt to amplify the effect via routine optimization. One of ordinary skill in the art would have a reasonable expectation of success leaving the chambers in for 48 hours because 1) Andrews teaches that removal of the chambers after 30 hours is optional and 2) one would reasonably deduce that leaving the chambers in longer would increase the effect of the chambers.
Response to Arguments
Applicant's arguments filed 07/02/2026 have been fully considered but they are not persuasive.
Applicant argues that the combined Andrews, Han and Zhang teachings do not demonstrate methods to successfully treat or vaccinate a subject with HCC. Applicant argues that the Han reference only discloses the use of a STAT3 decoy oligonucleotide to treat HCC, Zhang only discloses the use of an anti-IGF1R antibody on HepG2 cells and Andrews does not teach the treatment of HCC at all. Applicant asserts that neither Han nor Zhang teach or suggest the use of IGF1R AS ODN whatsoever. As such, Applicant argues a skilled would not reasonably expect that IGF1R AS ODN could be used to treat a subject having HCC as described in claims 18 and 29.
In response, Andrews teaches that the IGF1R AS ODN encapsulation/biodiffusion chamber method of Andrews is applicable to a wide variety of cancers and provides two definite criteria to determine whether or not a cancer is treatable using the IGF1R AS ODN encapsulation/biodiffusion chamber of Andrews: 1) the tumor cells must undergo apoptosis under the conditions in the biodiffusion chamber and 2) apoptosis of the tumor cells must elicit an anti-tumor response. Regarding the first criterion, the conditions in the biodiffusion chambers of Andrews comprise IGF1R AS ODN, which inhibits IGF1R by way of RNA antisense interactions. Zhang teaches that a different method of inhibiting IGF1R in HCC cells (an antibody) led to tumor cell apoptosis. Hence, it is reasonable for one of skill in the art to believe that HCC cells will undergo apoptosis in the presence of the IGF1R-inhibiting AS ODN present in the chambers of Andrews because Zhang teaches a different IGF1R inhibitor was able to induce apoptosis in HCC cells, thus fulfilling criterion 1). Regarding the second criterion, the teachings of Han demonstrate HCC cells undergoing apoptosis leads to an anti-tumor response. Hence, in view of the teachings of Han, HCC also satisfies criterion 2) of Andrews and, as such, HCC is therefore likely to be one of the types of tumors treatable using the biodiffusion chamber method of Andrews.
Applicant also argues that Zhang does not teach that anti-IGF1R antibodies necessarily induce apoptosis. Applicant focuses in on Zhang’s inability to reconcile how a lower dose of the anti-IGF1R antibody stimulated proliferation in vivo. Applicant submits that a skilled artisan reading Zhang would not arrive at the conclusion that inhibition of IGF1R leads to apoptosis of HCC cells because of this. In response, Applicant’s quotations are selective, out of context and do not convey the overall teaching of the Zhang reference. The fact that lower doses of the anti-IGF1R antibody stimulated cell growth by some unknown mechanism does not take away from the fact that the Zhang reference that, when in sufficient quantities to inhibit IGF1R, the IGF-1R inhibiting antibody did induce apoptosis in HCC cells.
Applicant also argues that Han does not teach blocking IGF-1R signaling induces apoptosis and/or an immune response. Applicant argues that Han is silent on IGF-1R inhibition/blockade and its ability to induce HCC apoptosis and/or any resultant anti-tumor response. Applicant argues that the Han teachings are limited to STAT3-induced apoptosis only and, because Han does not teach inhibition of IGF1R leads to apoptosis/any anti-tumor response, one of skill in the art would not reasonably expect to treat HCC by applying the teachings of Han to a different biological pathway. In response, the Han reference was applied only to address criterion 2 of Andrews: does apoptosis of the tumor cell elicit an anti-tumor response? The Han reference demonstrates that apoptotic HCC cells are capable of eliciting an anti-tumor response when apoptosis is STAT3-induced. It is very reasonable for one of skill in the art to extrapolate this to IGF1R-induced apoptosis, because both mechanisms end in the death of the tumor cells. Additionally, conclusive proof of efficacy is not required to show a reasonable expectation of success (see MPEP 2143.02 (I)). Applicant also argues that Zhang teaches away from the claimed subject matter, pointing to Zhang’s statement that anti-IGF1R antibodies may not be effective as a monotherapy in cancers displaying mitogen dependent proliferation. This is not relevant because in the claimed subject matter no IGF1R inhibitor is used as a monotherapy.
Applicant also points to alleged unexpected results, particularly Example 2 and Figure 1 of the instant disclosure demonstrating the instant claimed invention outperforming a mock treatment in an in vivo model as well as superior antibody titers. It is true that a prima facie case of obviousness may be rebutted by demonstration of unexpected results but the evidence must show unexpected results (see MPEP 716.02(a)). In the instant case the results are not unexpected because one of skill in the art would be likely to view HCC as treatable via the method of Andrews in view of the teachings of Han and Zhang and, as such, it would be expected to outperform a mock treatment.
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.
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Claims 18-19, 21, 25-27, 29 and 33-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. US 10,357,509 B2 in view of Andrews (Andrews, et al., WO 00/09145; Published 02/24/2000, of record) and Han (Han, et al., J. Exper. & Clin. Cancer Res (2017) 36:156, of record) and Zhang (Zhang, et al., World J Gastroenterology 2006 12(25):3977, of record).
Regarding claim 29 as well as the biodiffusion chamber referenced in claim 18, patented claim 1 is directed to a method of vaccinating a subject having brain cancer comprising steps that are identical to all of the step of claim 29 as well as patented SEQ ID NO: 1, which is the same as instant SEQ ID NO: 1. Regarding claims 19, 21 and 34, patented claim 3 is directed to a method comprising implanting 20 chambers for 48 hours. Regarding claim 33, patented claim 2 is directed toward a method of treating tumor cells for 18 hours prior to encapsulation. Regarding claims 25 and 35, the detailed method of treating brain cancer of patented claim 1 does not contain any steps that would elevate the cell temperature above body temperature or any steps comprising chemotherapy or radiation.
The ‘509 patent does not teach that the cancer treated is HCC. The ‘509 patent does not teach a second implantation using cells harvested at the same time as those of the first implantation or cells harvested after the first harvest, wherein the tumor has recurred or not responded.
Andrews teaches on the subject of methods of inducing regression of a tumor comprising treating a tumor cell ex vivo with a pro-apoptotic agent, placing the treated tumor cells in a diffusion chamber and inserting the chamber into a human for a therapeutically effective amount of time (Andrews, Abstract). Andrews teaches that the method of Andrews is capable of treating cancer using any tumor cells that undergo apoptosis and induce resistance or regression of tumor cells (Andres, p 6, lines 1-6). Andrews teaches that the pro-apoptotic agent of Andrews is a nucleic acid molecule directed against IGF-IR having the sequence of Andrews’ SEQ ID NO: 9 (same as instant SEQ ID NO: 1) (Andrews, p 7, line 20 – p 8, line 13). Andrews teaches that adherent cells are then treated with IGF-IR antisense oligonucleotide for 6-10 hours, placed in a diffusion chamber and irradiated with 6 Gy prior to implantation (Andrews, p 17, line 22- p 18, line 8). Andrews teaches that three patients who failed initial treatment were re-treated with a higher biological dose under FDA compassionate use (Andrews, p 24, lines 6-10).
Han teaches on the subject of whole cell tumor vaccines for HCC comprising HCC cells and a STAT3 decoy oligonucleotide (Han, Abstract- Background and Methods). Han teaches that whole cell vaccines often fail to demonstrate clinical benefit, with poor immunogenicity and immune tolerance/immunosuppression in the stromal microenvironment being possible explanations (Han, p 2, ¶ 2). Han teaches that STAT3 is overexpressed in many tumors and that previous findings confirmed blocking STAT3 signaling in HCC cells inhibited proliferation, promoted apoptosis and were sensitized to killing by NK cells, leading to the hypothesis that STAT3-blocked HCC cells could be used as a vaccine (Han, p 2, ¶ 3). Han teaches that vaccination with the decoy ODN yielded significantly smaller tumor volumes in BALB/c and C57BL/6 mice and longer survival times compared to scrambled ODN, lipofectamine or PBS (Han, Fig. 1).
Zhang teaches on the subject of IGF-IR inhibition in HCC (Zhang, Abstract). Zhang teaches that downregulation of IGF-IR function by antisense and dominant negative techniques reduces the growth and tumorigenicity of several cancer cell lines, thus rendering IGF-IR an attractive therapeutic target based on the hypothesis that inhibition would result in apoptosis and growth inhibition in tumor cells (Zhang, p 3978, ¶ 1). Zhang teaches that HepG2 HCC cells and Chang normal liver cells were treated with the IGF-IR inhibiting antibody aIR3 (Zhang, p 3978, ¶ 1-3). Zhang teaches that aIR3 both decreased cell growth (Zhang, Table 1) and increased apoptotic index (Zhang, Table 2) of the HepG2 HCC cells, both in dose-dependent manners.
It would be prima facie obvious to one of ordinary skill in the art to apply the biodiffusion method of the ‘509 patent to HCC view of the teachings of Andrews, Han and Zhang to arrive at a method of treating HCC comprising IGF-IR antisense-treated HCC cells used in the biodiffusion chamber of the ‘509 patent, wherein the HCC cells have been transfected with the STAT3 decoy ODN of Han and wherein there is IGF-IR antisense in the biodiffusion chamber of the ‘509 patent. One of ordinary skill in the art would be motivated to do this in order to better fight HCC. The method of Andrews is nearly identical to the method of the ‘509 patent and Andrews teaches that the method of Andrews can be used to treat any form of cancer so long as the cells associated with that cancer undergo apoptosis and the resultant cells are capable of inducing an immune response. One of ordinary skill would reasonably assume that the method of the ‘509 patent would work for these cancers as well. The teachings of Zhang demonstrate that IGF-IR inhibition is capable of inducing apoptosis in HCC and the teachings of Han demonstrate that apoptotic HCC cells can induce anti-tumor responses, which would lead one of ordinary skill to have a reasonable expectation of success using HCC cells in the method of the ‘509 patent.
It would be further obvious to one of ordinary skill in the art to conduct a second implantation of the biodiffusion chamber of the ‘509 patent comprising HCC cells, wherein the HCC cells obtained after the first cell harvest in the event that the tumor does not respond to the first implantation. One or ordinary skill in the art would be motivated to do this in order to treat hepatocellular cancer that has not responded fully to the first implantation. One of ordinary skill would have a reasonable expectation of success doing this because Andrews teaches subsequent implantations and the method of Andrews is nearly identical to the method of the ‘509 patent.
Response to Arguments
Applicant's arguments filed 07/02/2026 have been fully considered but they are not persuasive. Applicant’s argument/logic for this NSDP rejection is identical to Applicant’s logic for the 35 USC § 103 rejection and, as such, the same counterarguments apply.
Claims 18-19, 21, 25-27, 29 and 33-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. US 10,772,904 B2 in view of Andrews (Andrews, et al., WO 00/09145; Published 02/24/2000, of record) and Han (Han, et al., J. Exper. & Clin. Cancer Res (2017) 36:156, of record) and Zhang (Zhang, et al., World J Gastroenterology 2006 12(25):3977, of record).
Regarding claim 29 as well as the biodiffusion chamber referenced in claim 18, patented claim 1 is directed to a method of vaccinating a subject having brain cancer comprising steps that are identical to all of the step of claim 29 as well as patented SEQ ID NO: 1, which is the same as instant SEQ ID NO: 1. Regarding claims 19, 21 and 34, patented claim 3 is directed to a method comprising implanting 20 chambers for 48 hours. Regarding claim 33, patented claim 2 is directed toward a method of treating tumor cells for 18 hours prior to encapsulation. Regarding claim 35, patented claim 9 is directed to methods wherein the tumor cells are not exposed to temperatures above body temperature. Regarding claim 25, the detailed method of treating brain cancer of patented claim 1 does not contain any steps comprising chemotherapy or radiation.
The ‘904 patent does not teach that the cancer treated is HCC. The ‘904 patent does not teach a second implantation using cells harvested at the same time as those of the first implantation or cells harvested after the first harvest, wherein the tumor has recurred or not responded.
Andrews teaches on the subject of methods of inducing regression of a tumor comprising treating a tumor cell ex vivo with a pro-apoptotic agent, placing the treated tumor cells in a diffusion chamber and inserting the chamber into a human for a therapeutically effective amount of time (Andrews, Abstract). Andrews teaches that the method of Andrews is capable of treating cancer using any tumor cells that undergo apoptosis and induce resistance or regression of tumor cells (Andrews, p 6, lines 1-6). Andrews teaches that the pro-apoptotic agent of Andrews is a nucleic acid molecule directed against IGF-IR having the sequence of Andrews’ SEQ ID NO: 9 (same as instant SEQ ID NO: 1) (Andrews, p 7, line 20 – p 8, line 13). Andrews teaches that adherent cells are then treated with IGF-IR antisense oligonucleotide for 6-10 hours, placed in a diffusion chamber and irradiated with 6 Gy prior to implantation (Andrews, p 17, line 22- p 18, line 8). Andrews teaches that three patients who failed initial treatment were re-treated with a higher biological dose under FDA compassionate use (Andrews, p 24, lines 6-10).
Han teaches on the subject of whole cell tumor vaccines for HCC comprising HCC cells and a STAT3 decoy oligonucleotide (Han, Abstract- Background and Methods). Han teaches that whole cell vaccines often fail to demonstrate clinical benefit, with poor immunogenicity and immune tolerance/immunosuppression in the stromal microenvironment being possible explanations (Han, p 2, ¶ 2). Han teaches that STAT3 is overexpressed in many tumors and that previous findings confirmed blocking STAT3 signaling in HCC cells inhibited proliferation, promoted apoptosis and were sensitized to killing by NK cells, leading to the hypothesis that STAT3-blocked HCC cells could be used as a vaccine (Han, p 2, ¶ 3). Han teaches that vaccination with the decoy ODN yielded significantly smaller tumor volumes in BALB/c and C57BL/6 mice and longer survival times compared to scrambled ODN, lipofectamine or PBS (Han, Fig. 1).
Zhang teaches on the subject of IGF-IR inhibition in HCC (Zhang, Abstract). Zhang teaches that downregulation of IGF-IR function by antisense and dominant negative techniques reduces the growth and tumorigenicity of several cancer cell lines, thus rendering IGF-IR an attractive therapeutic target based on the hypothesis that inhibition would result in apoptosis and growth inhibition in tumor cells (Zhang, p 3978, ¶ 1). Zhang teaches that HepG2 HCC cells and Chang normal liver cells were treated with the IGF-IR inhibiting antibody aIR3 (Zhang, p 3978, ¶ 1-3). Zhang teaches that aIR3 both decreased cell growth (Zhang, Table 1) and increased apoptotic index (Zhang, Table 2) of the HepG2 HCC cells, both in dose-dependent manners.
It would be prima facie obvious to one of ordinary skill in the art to apply the biodiffusion method of the ‘904 patent to HCC view of the teachings of Andrews, Han and Zhang to arrive at a method of treating HCC comprising IGF-IR antisense-treated HCC cells used in the biodiffusion chamber of the ‘904 patent, wherein the HCC cells have been transfected with the STAT3 decoy ODN of Han and wherein there is IGF-IR antisense in the biodiffusion chamber of the ‘904 patent. One of ordinary skill in the art would be motivated to do this in order to better fight HCC. The method of Andrews is nearly identical to the method of the ‘904 patent and Andrews teaches that the method of Andrews can be used to treat any form of cancer so long as the cells associated with that cancer undergo apoptosis and the resultant cells are capable of inducing an immune response. One of ordinary skill would reasonably assume that the method of the ‘904 patent would work for these cancers as well. The teachings of Zhang demonstrate that IGF-IR inhibition is capable of inducing apoptosis in HCC cells and the teachings of Han demonstrate that apoptotic HCC cells are capable of eliciting an anti-tumor response, which would lead one of ordinary skill to have a reasonable expectation of success using HCC cells in the method of the ‘904 patent.
It would be further obvious to one of ordinary skill in the art to conduct a second implantation of the biodiffusion chamber of the ‘904 patent comprising HCC cells, wherein the HCC cells obtained after the first cell harvest in the event that the tumor does not respond to the first implantation. One or ordinary skill in the art would be motivated to do this in order to address the lack of response to the first implantation. One of ordinary skill would have a reasonable expectation of success doing this because Andrews teaches subsequent implantations and the method of Andrews is nearly identical to the method of the ‘904 patent.
Response to Arguments
Applicant's arguments filed 07/02/2026 have been fully considered but they are not persuasive. Applicant’s argument/logic for this NSDP rejection is identical to Applicant’s logic for the 35 USC § 103 rejection and, as such, the same counterarguments apply.
Conclusion
Claims 18-19, 21, 25-27, 29 and 33-35 are rejected.
No Claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SYDNEY VAN DRUFF/ Examiner, Art Unit 1643
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643
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