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 .
Current Status of 17/769,502
This Office action is responsive to the Applicant remarks and amended claims of 12/17/2025. Claims 1-10 are pending and have been considered on the merits.
Priority
The instant application is a national stage entry of PCT/SE2020/050978, filed 10/14/2020, which claims priority to SE1951181-5, filed 10/18/2019.
Response to Arguments and Amendments
Amendments
Applicants have amended the specification and the drawings to correct typographical errors. The previous objections to the drawings and specification are withdrawn.
Applicants have corrected the typographical errors of claims 1-3. The previous object is withdrawn.
Arguments
Applicants’ argument regarding the 112(a) rejections of claims 1-10 have been fully considered and are found persuasive. The previous rejection is withdrawn.
Applicant’s arguments regarding the 103 rejections of claims 1-10 have been fully considered but are not found persuasive.
Regarding the rejection of claims 1-9, Applicants argue that the Examiner's position relies upon hindsight reasoning to arrive at the instant invention. Applicants assert that the Examiner has improperly generalized cancers susceptible immunotherapy and further contend that desloratadine would not have been and obvious therapeutic agent for the treatment of such cancers. These arguments have been fully considered but are not persuasive.
Applicants rely on the performance of other antihistamines disclosed in Olsson, asserting that because certain antihistamines exhibited neutral or detrimental effects on cancer survival, the artisan would not have been motivated to use desloratadine in the treatment of cancer. However, the rejection does not rely on antihistamines as a class. Rather, the rejection is based specifically on the teachings of Olsson regarding desloratadine. Olsson discloses that administration of desloratadine was associated with improved survival in cancer patients and further teaches that desloratadine is useful in treating cancers susceptible to immunotherapy. In view of this teaching, the performance of other antihistamines disclosed in Olsson does not negate the motivation to investigate or administer desloratadine for cancers falling within this category. The obviousness analysis is directed only to desloratadine and the teachings of the references regarding that compound, not to antihistamines broadly.
Applicants further argue that Kantoff merely establishes that certain cancers are suitable candidates for immunotherapy and does not teach the use of antihistamines generally, or desloratadine specifically in the treatment of cancer. However, Kantoff was relied upon not to teach the therapeutic use of desloratadine. Rather, Kantoff was cited to establish that prostate cancer is recognized in the art as being susceptible to immunotherapy. Accordingly, Kantoff serves to identify prostate cancer as a member of the class of cancers that Olsson expressly teaches may be treated using desloratadine.
The Applicants additionally contend that the Examiner has relied on hindsight reasoning to bridge the alleged gap between the references. The record does not support this characterization. Olsson expressly teaches the use of desloratadine for the treatment of cancers susceptible to immunotherapy (see claim 15). References Kantoff, Kato, Doroshow, Chen, and Rosen each identify specific cancers that are recognized in the art as being susceptible to immunotherapy. In view of these teachings, the artisan would have understood that cancers identified as immunotherapy-susceptible fall within the category of cancers that Olsson teaches may be treated with desloratadine.
Olsson expressly teaches that desloratadine is useful in the treatment of cancers susceptible to immunotherapy and claims a method of treating such cancers using desloratadine. In the absence of evidence that Olsson's disclosure is non-enabling or inoperative, this teaching provides both motivation to administer desloratadine to cancers known to be susceptible to immunotherapy and a reasonable expectation of success in doing so.
Regarding the rejection of claims 1, 8, and 10, Applicants reiterate their contention that desloratadine is non-obvious discussed above. This argument is unpersuasive for the same reasons previously discussed. Applicants argue that desloratadine is not a conventional cancer therapy and therefore would not have been combined with an immune checkpoint inhibitor (ICI) as discussed in Patel. However, the rejection does not rely on desloratadine being a conventional therapy. Rather, Olsson teaches that desloratadine is useful for treating cancers susceptible to immunotherapy, thereby identifying desloratadine as an agent relevant to immunotherapeutic cancer treatment. Patel describes frameworks for rationally designing combination therapies that enhance immune-mediated tumor control, including combinations involving immune checkpoint inhibitors. In view of Olsson's teachings that desloratadine is useful in cancers susceptible to immunotherapy, the artisan would have been motivated to consider combining desloratadine with and ICI consistent with the combination therapy strategy disclosed by Patel.
Applicants further assert that the interaction between desloratadine and an ICI would have been unpredictable and could have resulted in antagonism or no therapeutic effect. These assertions are speculative and are unsupported by evidence. The obviousness inquiry does not require certainty or a complete understanding of the mechanism of action, but rather a reasonable expectation of success. In view of Olsson's teaching that desloratadine is useful in cancers susceptible to immunotherapy and Patel's teaching that ICIs are combined with other agents to enhance treatment efficacy, the artisan would have had a reasonable expectation that combing desloratadine with and ICI could improve cancer treatment outcomes.
Claim Rejections - 35 USC § 103 (Maintained)
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 for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Olsson (WO 2016/116438 A1, found in IDS filed 04/15/2022) in view of Kantoff (Kantoff, Philip W et al. “Sipuleucel-T immunotherapy for castration-resistant prostate cancer.” The New England journal of medicine vol. 363,5 (2010): 411-22. doi:10.1056/NEJMoa1001294 ), Kato (Kato, Ken et al. “A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2).” Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association vol. 22,2 (2019): 344-354. doi:10.1007/s10120-018-0899-6), Doroshow (Doroshow, Deborah B., et al. "Immunotherapy in non–small cell lung cancer: facts and hopes." Clinical Cancer Research 25.15 (2019): 4592-4602), Chen (Chen, Jiang et al. “Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.” Journal of immunology research vol. 2017 (2017): 8282391. doi:10.1155/2017/8282391), and Rosen (Rosen, Lee S., Ira A. Jacobs, and Ronald L. Burkes. "Bevacizumab in colorectal cancer: current role in treatment and the potential of biosimilars." Targeted oncology 12 (2017): 599-610.).
Determining the scope of the prior art:
Olsson teaches the following:
A method of treating breast cancer through administering desloratadine to a patient diagnosed with breast cancer (Abstract, claim 1).
Desloratadine for use in treatment of a patient diagnosed with a cancer type susceptible to immunotherapy (Abstract, claim 15).
The treatment is continuous for at least 50 days, preferably at least 100 days and most preferably at least 400 days (claim 4), reading on instant claims 1 and 6.
The daily dose of desloratadine corresponds to the defined daily dose (DDD) (claim 7), reading on instant claim 4.
The dose of desloratadine is between 2.5 to 45 mg per day (claim 8), reading on instant claim 5.
In addition to the desloratadine treatment, the patient is further treated with radiotherapy, chemotherapy, and/or hormonal treatment (claim 14), reading on instant claims 8 and 9.
Primary prophylaxis corresponds to preventive treatment of an initial disease, secondary to reducing the incidence of recurrence or reactivation of a pre-existing disease, tertiary to a continuous treatment started after the onset of a disease to mitigate further damage, and periodic to treatment given for shorter periods of time (specification, pg. 10 lines 6-15), reading on instant claim 7.
Kantoff teaches that prostate cancer is susceptible to immunotherapy. More specifically that the use of the immunotherapeutic agent sipuleucel-T prolonged overall survival among men with metastatic castration resistant prostate cancer (pg. 411, Conclusions).
Kato teaches that gastric cancer is susceptible to immunotherapy. The use of the PD-1 inhibitor nivolumab in patients with advanced gastric and/or gastro-esophageal junction cancers resulted in patients having a manageable safety profile and longer overall survival, with early and durable responses in comparison to patients treated with placebo.
Doroshow teaches that non-small cell lung cancer is susceptible to immunotherapy. Immune-checkpoint inhibitors, particularly inhibitors of the PD-1 axis, have demonstrated their ability to improve outcomes in second-line or later therapy of advanced disease and were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-1 on at least 50% of cells (pg. 4592, abstract).
Chen teaches that pancreatic cancer is susceptible to immunotherapy. Specific immunotherapy can result in prolonged overall survival in patients. The specific immunotherapy-mediated improvements typically correspond to enhanced immunity function and serum cancer marker inhibitions (pg. 15, left column, first full paragraph).
Rosen teaches that colorectal cancer is susceptible to immunotherapy. Bevacizumab has demonstrated improved overall survival for patients with metastatic colorectal cancer (pg. 599, Key Points).
Ascertaining the differences between the prior art and the claims at issue:
Olsson does not explicitly teach the claimed species of cancer.
Kantoff does not teach the treatment of prostate cancer with desloratadine.
Kato does not teach the treatment of gastric cancer with desloratadine.
Doroshow does not teach the treatment of non-small cell lung cancer with desloratadine.
Chen does not teach the treatment of pancreatic cancer with desloratadine.
Rosen does not teach the treatment of colorectal cancer with desloratadine.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in organic chemistry, medicinal chemistry, pharmaceutical sciences, or a related field. The artisan would have experience in the development of cancer treatment regimens and would be familiar with combination therapies.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to investigate the use of desloratadine for the treatment of additional cancers known to be susceptible to immunotherapy, based on the teachings of Olsson. Given the established responsiveness of prostate, gastric, lung, pancreatic, and colorectal cancer to immunotherapeutic treatment, the artisan would have reasonably expected that these cancers would be ideal candidates for similar treatment. The artisan would have been motivated to administer treatment of these additional species of cancer using the protocol outline by Olsson based on the method’s demonstrated efficacy in the treatment of breast cancer. The artisan would have expected that the protocol taught by Olsson, having shown clinical benefit in an immunotherapy-relevant context, would serve as an appropriate and logical starting point for assessing the therapeutic utility of desloratadine in other immunotherapy-susceptible cancers.
Claims 1, 8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Olsson, Kantoff, Kato, Doroshow, Chen, and Rosen in view of Patel (Patel, Shetal A., and Andy J. Minn. "Combination cancer therapy with immune checkpoint blockade: mechanisms and strategies." Immunity 48.3 (2018): 417-433.).
Determining the scope of the prior art:
The teachings of Olsson, Kantoff, Kato, Doroshow, Chen, and Rosen are discussed above and are incorporated by reference into this rejection. The combined teachings of the references above teach claims 1 and 8, see discussion above.
Patel teaches that immune checkpoint blockade (a method of cancer treatment involving the administration of immune checkpoint inhibitors) is frequently employed in combination with conventional therapeutic strategies. Such combination therapies are well-established in the art and are often used to enhance treatment efficacy, with some patients experiencing improved clinical responses in comparison to the monotherapy (Introduction).
Ascertaining the differences between the prior art and the claims at issue:
Olsson, Kantoff, Kato, Doroshow, Chen, and Rosen do not teach the use of immune checkpoint inhibitors in combination with desloratadine.
Patel does not teach the use of immune checkpoint inhibitors in combination with desloratadine.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in organic chemistry, medicinal chemistry, pharmaceutical sciences, or a related field. The artisan would have experience in the development of cancer treatment regimens and would be familiar with combination therapies.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to use desloratadine in combination with an immune checkpoint inhibitor based on the well-established clinical benefit of combination immunotherapies in the treatment of cancers known to be susceptible to immune modulation. Give that immune checkpoint inhibitors are routinely combined with other therapeutic agents to improve response rates and overcome resistance, the artisan would expect that incorporating desloratadine could enhance anticancer activity in other immunotherapy susceptible cancers. These cancers would be viewed as promising candidates for such combination approaches. The artisan would expect that administering desloratadine in combination with an immune checkpoint inhibitor would increase the likelihood of achieving a meaningful therapeutic response.
Conclusion
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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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625