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 amended claims and Applicant remarks of 07/15/2026. Claims 1 and 3-10 are pending and have been examined 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
Applicants allege that the Examiner’s position is an oversimplification of the Olsson reference and that it ignore the “teaching away” of the reference. Applicants further allege that Olsson presents data for additional H1-antihistamines. The presented data show that desloratadine and ebastine had positive effects and other structurally related H1-antihistamines had no effect or detrimental effects. Applicants allege that this “clearly paints a picture of extreme unpredictability.”
Applicants then extrapolate from this point that the artisan might have been discouraged from selecting desloratadine for the treatment of the instantly claimed cancers due to broad teachings of antihistamines being detrimental. Applicants contend that the teachings of Olsson do not teach that desloratadine is a promising therapeutic for immunotherapy-susceptible cancers but would rather take the teachings to be “the effect of any antihistamine on any given cancer is unknown and requires patient data for validation.” Applicants further allege that the selection of desloratadine from the group consisting of desloratadine and ebastine constitutes hindsight reconstruction and that the artisan would not have been lead to reasonably select desloratadine without the aid of the instant disclosure.
These arguments have been fully considered and are not found persuasive. Applicants have mischaracterized and misrepresented the teachings of Olsson. Olsson discloses desloratadine or ebastine for use in treatment of a patient diagnosed with breast cancer or a cancer type susceptible to immunotherapy (Abstract, Claims 1 and 15). The reference does not broadly teach the use of all antihistamines or even the use of all H1 receptor antihistamines for the treatment of breast cancer or immunotherapy susceptible cancers. Instead, the reference focuses solely on the use of desloratadine or ebastine for the therapeutic methods. These two compounds improved prognosis and increased the survival rate in breast cancer patients (pg. 5, lines 12-15). Applicants reference Figures 2-6 as allegedly demonstrating the unpredictable nature of antihistamines for the treatment of immunotherapy susceptible cancers and conclude that the artisan would therefore regard the efficacy of such compounds as unknown absent patient data. However, interpreting the poorer performance of the comparator antihistamines of Figs 2-6 as negating the favorable results obtained with desloratadine and ebastine would disregard the very distinction demonstrated by the reference. Such an interpretation is not consistent with how a person of ordinary skill in the art would reasonably understand the reported data.
The reference is directed to the use of desloratadine and ebastine for the treatment of breast cancer and other immunotherapy susceptible cancers and further explains that if the observed antihistamine effect is due to an immunological mechanism, other tumor types may similarly exhibit positive survival effects (pg. 8 line 33-pg. 9 line 5). The reference goes on to identify several additional cancer types in this context. This provides clear motivation to investigate desloratadine and ebastine in other immunotherapy-susceptible cancer.
The reference provides a clear teaching for the selection of desloratadine. Olsson teaches that second-generation H1-antihistamines are more selective for peripheral H1 receptors as opposed to CNS H1 receptors and cholinergic receptors (pg. 6, lines 13-17). Desloratadine is expressly taught as having the most pronounced effects of the second-generation H1-antihistamines. Desloratadine is taught as having a much higher volume of distribution resulting in higher tissue distribution and a long half-life providing fairly complete blocking of basal H1 signaling in almost all tissues and organs, including tumors (pg. 6, lines 18-25).
Applicants’ arguments that the instantly claimed cancers do not constitute a recognized class because Olsson does not expressly recite each of the claimed cancers, and that the rejection therefore relies on hindsight reconstruction have been considered but are not persuasive. As discussed above, Olsson expressly teaches that treatment with desloratadine or ebastine may produce positive survival effects in other immunotherapy-susceptible cancer types. This teaching would have led the artisan to investigate the use of desloratadine or ebastine in other cancers known to be susceptible to immunotherapy and therefore provides a clear motivation to apply these antihistamines to such cancers. No hindsight reconstruction is required. Olsson itself provides the motivation, while the secondary references identify specific cancers recognized in the art as susceptible to immunotherapy.
Applicants’ arguments that desloratadine would not have been considered sufficiently reliable cancer therapies to combine with immune checkpoint inhibitors is not persuasive. Olsson expressly teaches the use of desloratadine in combination with other established cancer therapies based on a possible immunological mechanism. The secondary reference Patel teaches immune checkpoint inhibitors as a known form of immunotherapy. In view of Olsson’s teachings, the artisan would have had a reason to investigate the combination of the promising antihistamine of Olsson with a known immunotherapeutic agent, without aid from the instant disclosure.
Applicants arguments of unexpected results have been considered and found persuasive. While the references discussed above provide a clear motivation to investigate the use of desloratadine for the treatment of additional immunotherapy-susceptible cancers, the artisan would not have reasonably expected the claimed treatment regimen to produce the magnitude of benefit demonstrated by Applicants in the instant application. Applicants show that the instantly claimed treatment regimen increase the 5-year survival rate in pancreatic cancer patients from 8% to 35%. By comparison, the observed improvement in 5-year survival for other treated cancers (gastric and lung) was about 5%. The substantially greater survival rate in pancreatic cancer would not have been expected from the teachings of the prior art and is sufficient to rebut the previous rejection of obviousness.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 3-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating the recited cancers by administering desloratadine, does not reasonably provide enablement for the prophylactic treatment of the claimed cancers using desloratadine. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to methods of treatment, including prophylactic treatment of cancers comprising administering desloratadine to a subject having one of the claimed cancers. Page 11, lines 9-21 of the specification define prophylaxis as including primary prophylaxis which refers to the preventative treatment of an initial disease. Thus, the claims taken together with the specification imply that the administration of desloratadine to a patient will prevent the occurrence of lung cancer, prostate cancer, pancreatic cancer, gastric cancer, and colorectal cancer.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The state of the art is that no general procedure is art-recognized for determining which patients generally will suffer from the claimed diseases before the fact. The state of the art is that cancer is not preventable (see American Cancer Society https://www.cancer.org/cancer/risk-prevention.html). It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved" and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed diseases. The “prophylactic” treatment of the claimed cancers would require a method of identifying those individuals who will develop the claimed cancers before they exhibit symptoms. There is no evidence of record that would guide the artisan to identify those patients with the potential of becoming afflicted.
(5) The relative skill of those in the art:
The artisan would have experience in the field of organic chemistry, medicinal chemistry, pharmaceutical sciences, oncology, pharmacology, or a related field. The artisan would have experience in the development, screening, and evaluation of potential anticancer therapeutic agents. The artisan would further be familiar with conventional methods for assessing therapeutic activity and interpreting preclinical and clinical data relating to the treatment of cancer.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification has provided guidance for treatment regimens using desloratadine, including specific daily dosage ranges (pg. 9, line 24 – pg. 10 line 5) and minimum treatment durations (pg. 9 lines 7-15). The specification further provides clinical registry data demonstrating improved survival associated with desloratadine administration in patients diagnosed with several of the studied cancers (Figs. 1 and 7-18).
However, the specification does not provide data supporting the prophylactic treatment of cancer as claimed. Specifically, the instant disclosure does not provide relevant data demonstrating that administration of desloratadine prevents the initial occurrence of cancer in any patient population. Rather, the experimental data are directed to patients already diagnosed with cancer and concern the effect of desloratadine administration on cancer-specific survival following diagnosis.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to the absence of established prophylactic treatments for preventing the initial occurrence of the claimed cancers and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
Conclusion
Claims 1 and 3-10 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONNOR KENNEDY ENGLISH whose telephone number is (571)270-0813. The examiner can normally be reached Monday Friday, 8 a.m. 5 p.m. ET..
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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
