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 .
DETAILED ACTION
1. The Amendment filed January 13, 2026 in response to the Office Action of July 14, 2025 is acknowledged and has been entered. Claims 2, 4-8, 12-19, 21, 23-27, 31-34 and 39-49 have been cancelled. Claims 3, 9, 11, 20, 22, and 28 have been amended. Claims 36-38 were previously withdrawn as being drawn to a nonelected invention.
2. Claims 1, 3, 9-11, 20, 22, 28-30, and 35 are currently being examined.
Rejections Maintained
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
3. Claims 1, 3, 9-11, 20, 22, 28-30 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2012/135408 A1 (Sharma, M. et al. Oct. 4, 2012, IDS), “Sharma” evidenced by Wen and Kesari (New England Journal Med. 2008 359:492-507, IDS “Wen”, in view of Zeng et al. (International. J. Radiation Oncology Biology Physics June 2013 86(2): 343-349, IDS), “Zeng” and in view of US Pat. No. 8,129,184 (Yu, JS March 6, 2012, IDS), “Yu” for the reasons of record set forth below.
Sharma teaches treating cancer, including glioblastoma, with PD-1 blocking antibodies, such as humanized anti-PD1 monoclonal antibody h409A11, which bind PD-1. See p. 2-¶ 0007, p. 7- ¶ 0046, and pp. 9-10-¶¶0052-0054 and claim 25.
Wen teaches that glioblastoma is a malignant glioma. See Wen p. 492-1st paragraph of Epidemiologic Features.
Sharma teaches that the anti-PD-1 antibody can be used in combination with dendritic cells pulsed with tumor derived antigens. See pp. 12-¶ 0057.
With respect to claims 10, 11, 29 and 30 , the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. See MPEP 2144.04 IV(C).
Sharma teaches treating patients with additional cancer treatments including chemotherapy, radiotherapy or other antibody targeting therapies. See pp. 12-¶ 0057.
Sharma does not specifically provide an example of treatment of glioblastoma with an anti-PD1 antibody or that the dendritic cells were pulsed caner lysates produced from a human malignant glioma.
Zeng teaches treatment of glioblastoma with anti-PD-1 antibodies and stereotactic radiosurgery in an intracranial glioma mouse model. See Summary, Abstract and Fig. 1. Zeng teaches that treatment with anti-PD-1 antibodies or radiation alone improved survival with the combination of the two treatments giving the greatest long-term survival. See Summary, Abstract, Results-p. 346 and Fig. 2. Zeng teaches that combination treatment increased the cytotoxic T cell to regulatory T cell ratio. See p. 347- and Figure 4.
Yu teaches treating glioblastoma with dendritic cells pulsed with glioblastoma cancer stem cell lysates. See column 3-lines 10-20, paragraph bridging columns 7 and 8, column 8--lines 55-65, claims 1-5 and Fig. 1.
Yu teaches that the dendritic antigen presenting cells can be isolated from a human. See column 20-lines 52-65 and column 21-lines 14-16.
Yu teaches immunization of animals with dendritic cells pulsed with antigens from isolated cancer stem cells provided a significant survival benefit as compared to immunization with dendritic cells pulsed with differentiated tumor cells. See paragraph bridging columns 1 and 2 and Example 10.
Yu teaches that the dendritic cell vaccinations may be accompanied by other treatments. See column 21-lines 53-63.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high (e.g. a physician) to combine the teachings of Sharma, Zeng and Yu and prolong the effects of treatment of glioblastoma with the anti-PD1 antibodies of Sharma in combination with human dendritic cells pulsed with human glioblastoma cancer cell lysates alone or with additional therapies because Sharma teaches treating glioblastoma with PD-1 blocking antibodies in combination with dendritic cells pulsed with tumor derived antigens, Zeng teaches that treatment with anti-PD-1 antibodies or radiation alone improved survival with the combination of the two treatments giving the greatest long-term survival, and Yu teaches treating glioblastoma with dendritic cells pulsed with glioblastoma cancer stem cell lysates, using human dendritic cells and combining the dendritic cells with other therapies. One would have been motivated to combine the glioblastoma lysate pulsed human dendritic cells of Yu with the anti-PD1 antibodies of Sharma or Zeng to prolong the effects of treatment of glioblastoma because Yu teaches dendritic cells pulsed with antigens from isolated cancer stem cells provided a significant survival benefit.
Response to Arguments
4. Applicant argues that it seems that the Office is using the present disclosure to find and combine references in impermissible hindsight reconstruction of the present claims. Sharma discloses the production of human anti-PD-1 antibodies and their compositions. In boilerplate sections of the application, it is asserted that the antibodies can be used to treat just about any cancer whether it has been shown to be responsive to immunotherapy or not. Sharma discloses that in most preferred cancers for treatment with anti-PD-1 antibodies, neither glioma or glioblastoma multiforme are listed. Sharma also discloses that the anti-PD-1 antibodies of the disclosure can be combined with essentially any known anticancer therapy. It is well known in the art that there is no or a very weak response when inhibitors of checkpoint proteins are combined with some anticancer therapies.
Applicant argues that Wen and Kesari merely disclose that glioblastoma is a malignant glioma which adds nothing to the rejection overall.
Applicant argues that Zeng discloses the combination of anti-PD-1 antibodies and stereotactic radiosurgery in an intracranial glioma mouse model. The Office has noted that the anti-PD-1 antibodies or radiation when used alone improved survival and that in combination gave the greatest improvement in long-term survival. While such a disclosure may suggest the combination of anti-PD-1 antibodies with radiation treatments, there is no reasonable expectation for one of ordinary skill in the art that the combination of anti-PD-1 antibodies with a glioma lysate pulsed dendritic cell will show any effect, much less an improvement over anti-PD-1 antibodies when used alone. Radiation therapy and a dendritic cell vaccine work through different mechanisms and any result with one or the other cannot be used to predict a result with the other.
Applicant argues that Yu is asserted by the Office to disclose treating glioblastoma with dendritic cells pulsed with glioblastoma cancer stem cell lysate. However, what is taught by Yu is the use of dendritic cells pulsed with cancer stem cell antigens which are very different from glioma or glioblastoma tumor cell lysate. In Yu, the excised glioma or glioblastoma tumor is processed to form cancer stem cells. In particular, the tumors are enzymatically dissociated, plated as a monocellular suspension, and cultured with EGF and bFGF to form tumor neurospheres. These tumor neurospheres are very different from the original tumor cells when excised from a patient. Any result obtained with these cancer stem cells cannot be extrapolated to a glioma tumor cell lysate.
Applicant argues that as such, even if one of ordinary skill in the art were to combine the actual teachings and not speculations of Sharma, Wen, Zeng, and Yu, the method disclosed is the combination of anti-PD-1 antibodies with tumor neurosphere lysate pulsed dendritic cells for treating a cancer. In the case of the most preferred cancers disclosed by Sharma, the cancers would be ovarian, renal, colorectal, pancreatic, breast, liver, gastric, esophageal, and melanoma. Although there might be some suggestion of the pending claims, there is no reasonable expectation that the claimed combination would enhance or prolong the effects of a glioma lysate pulsed dendritic cell vaccine or the effects of an inhibitor of a checkpoint protein. Respectfully, Applicants must assert that the Office has failed to set forth a prima facie case for rejecting Claims 1, 3, 9-11, 20, 22, 28-30, and 35 as being obvious over Sharma, as evidenced by Wen, in view of Zeng, and further in view of Yu.
Applicant argues that an view of the above amendments and remarks, the Office is respectfully requested to reconsider and withdraw the rejection of Claims1, 3, 9-11, 20, 22, 28-30, and 35 under 35 U.S.C. § 103 as being unpatentable over Sharma, as evidenced by Wen, in view of Zeng and in view of Yu.
5. Applicant's arguments have not been found persuasive and the rejection is maintained. In response to Applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Given that the rejection does not use knowledge taken from Applicant’s disclosure the rejection is proper.
In regard to Sharma teaching of treatment of various cancers, including glioblastoma with PD-1 blocking antibodies Applicant appears to be arguing that Sharma is not enabled for treatment of the various cancers. However MPEP 2121 (I) states
When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to provide facts rebutting the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07.
Applicant has not provided any facts to show that the teachings of Sharma are not enabled. Although Applicant argues that there is no or a very weak response when inhibitors of checkpoint proteins are combined with some anticancer therapies, arguments of counsel cannot take the place of evidence in the record. See MPEP 716.01 (c)(II) and In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Additionally, Zeng teaches that treatment of glioblastoma with anti-PD-1 antibodies or radiation alone improved survival with the combination of the two treatments giving the greatest long-term survival, providing support for the teachings of Sharma that anti-PD-1 antibodies can be used for treatment of glioblastoma. Although Sharma does not teach treating glioblastoma as a preferred embodiment, the prior art is relevant for it contains and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See MPEP 2123 (I)(II) and In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Thus, Applicant’s arguments with respect to Sharma are not found persuasive.
Regarding the arguments against Zheng, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Sharma already taught that the anti-PD-1 antibody can be used in combination with dendritic cells pulsed with tumor derived antigens for treatment of cancers like and glioblastoma. Zheng provides motivation to treat glioblastoma, in particular, because Zeng teaches that treatment of glioblastoma with anti-PD-1 antibodies or radiation alone improved survival with the combination of the two treatments giving the greatest long-term survival. Thus, one would have been motivated to treat glioblastoma with the anti-PD-1 antibody methods of Sharma given the effective treatment of glioblastoma taught by Zeng.
Regarding Yu and the argument that the glioblastoma stem cell lysate of Yu is not the same as the claimed cancer lysate produced from a human malignant glioma, this argument is not found persuasive because the glioblastoma stem cell lysate of Yu is a species of the claimed genus of cancer lysate produced from a human malignant glioma. The claims do not exclude the processing steps used by Yu to obtain the lysate or limit the cancer lysate to a particular type of glioma cell. Thus given that Yu teaches treating glioblastoma with dendritic cells pulsed with glioblastoma cancer stem cell lysates, using human dendritic cells and combining the dendritic cells with other therapies, one would have been motivated to combine the glioblastoma lysate pulsed human dendritic cells of Yu with the anti-PD1 antibodies of Sharma or Zeng to prolong the effects of treatment of glioblastoma because Yu teaches dendritic cells pulsed with antigens from isolated cancer stem cells provided a significant survival benefit.
In view of the foregoing, when all of the arguments and evidence are considered, the totality of the arguments and rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness as previously set forth and above. Thus the rejection is maintained for the reasons of record.
Conclusion
6. All other objections and rejections recited in the Office Action of July 14, 2025 are withdrawn.
7. No claims allowed.
8. 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 extension fee 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.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached on M-F 8:30-5:30 Eastern Time
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/Peter J Reddig/
Primary Examiner, Art Unit 1642