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 .
Claim Status
Claims 1, 8, 15, 21, 23, 30, 35, 37, 52-53, 58-66, 68, and 70-82 are under consideration in this office action.
Maintained Rejections
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.
Claims 1, 8, 21, 23, 30, 35, 37, 52-53, 58-65, 68, and 70-82 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0155436, published June 7, 2018 (“Orengo”; PTO-892 from 8/25/2022).
Claims 1, 52, and 62-63 are directed to a method of reducing the annualized rate of AECOPD in a patient with COPD who does not currently smoke. The method comprises a step of administering an antibody against IL-33, a cytokine involved in inflammation.
Orengo teaches a method for treating patients with moderate-to-severe COPD with an IL-33 antibody [0326]. This method reduces the incidence of COPD exacerbations, wherein an exacerbation is an increase in the severity and/or frequency and/or duration of one or more symptoms as well as any deterioration in the respiratory health of a subject that requires a therapeutic intervention, such as corticosteroids [0161], as in the preamble of claims 1, 52, and 62-63 drawn to a method of reducing AECOPD.
The IL-33 antibody of Orengo is comprised of HCDR1-3 of SEQ ID NOs: 276, 278, and 280 and LCDR1-3 SEQ ID NOs: 284, 286, and 288 [0064], as in the antibody of instant claims 1 and 52 comprised of HCDR1-3 of SEQ ID NOs: 4, 6, and 8 and LCDR1-3 of SEQ ID NOs: 12, 14, and 16, respectively. This antibody taught by Orengo is comprised of heavy chain variable region (HCVR) and light chain variable region (LCVR) sequence pair of SEQ ID NO: 274 and SEQ ID NO: 282 [0013] and heavy chain and light chain sequence pair SEQ ID NO: 354 and SEQ ID NO: 355 [see sequence listing]. The HCVR and LCVR sequence pair of Orengo is the same as the HCVR and LCVR sequence pair of SEQ ID NO: 2 and SEQ ID NO: 10 of instant claims 53 and 59. The heavy chain and light chain sequence pair of Orengo is the same as the heavy chain and light chain sequence pair of SEQ ID NO: 18 and SEQ ID NO: 20 of instant claims 60 and 62-63.
Claims 1, 52, and 62-63 recite the limitation wherein the subject with COPD does not currently smoke; Orengo teaches treatment of a patient with COPD who is a former smoker (i.e. a COPD subject who does not currently smoke) with an IL-33 antibody alone [0332]. The subjects of Orengo include former smokers with a smoking history of ≥ 10 packs/year [0332], as in claims 68 and 70-72. In some embodiments, the method of treatment is directed to moderate-to-severe COPD [0326], as instant claim 21.
Although Orengo teaches a method for treating COPD in former smokers, Orengo does not explicitly define former smoker as one who has stopped smoking for at least 6 months, as required by claims 68, 70-82. However, there is no evidence for criticality in the method for treating former smoker who stopped smoking for at least 6 months. It would have been prima facie obvious to the ordinary artisan to treat a former smoker who had stopped smoking at least 6 months. According to the instant specification, the duration of smoking cessation was as low as 1.2 months and as high as 56.1 years, with a mean of 11.8 years and a median of 9.92 years [00324]. To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960); see MPEP716.02(d).II. In the absence of any criticality regarding a former smoker who stopped smoking 6 months ago, the instant claims are obvious over the method of Orengo.
Regarding the improvement in various COPD-associated parameters with anti-IL-33 antibody in claims 1, 23, 52, 58, and 61-63, while Orengo is silent on the intended results of the effect of the anti-IL-33 antibody on clinical outcome in patients with COPD who were former smokers, it is clear that the same patient population treated with the same antibody would have the same characteristics and effects as the instantly claimed antibody since there is no evidence to the contrary. Note that rejections for anticipation are appropriate when the prior art discloses a method (or product) that appears to be identical except that the art is silent as to an inherent property; see MPEP § 2112(III). In such situations, the burden is on applicant to provide evidence that the prior art product (or method) is not the same.
With regard the doses of claims 30, 52, 62-63, and 77-78, Orengo teaches a therapeutically effective amount of IL-33 antibody antagonist that can be about 0.1 mg to about 600 mg, about 100 mg to about 400 mg, and about 300 mg [0221].
With respect to the dosing interval of claims 62-64 and 73-76, Orengo teaches a method to administer the antibody once a week, once every two weeks, once every three weeks, once a month, and once every two months [0236].
The background therapy of Orengo includes inhaled corticosteroid (ICS) and/or a long acting 2 adrenergic agonist (LABA) and/or a long acting muscarinic agonist (LAMA); double therapy: LABA+LAMA or ICS+LABA or ICS+LAMA; or triple therapy: ICS+LABA+LAM [332], as in the limitations of instant claims 1, 52, and 62-63.
Regarding claims 8 and 65, Orengo teaches methods of treating patients with COPD comprising anti-IL-33 antibody therapy in addition to a background therapy comprising ICS, LABA, and/or LAMA [0044]. Although Orengo does not explicitly state that the patients with COPD receiving antibody therapy are not well-controlled on a background therapy of LABA/LAMA/ICS, it would be obvious to one of ordinary skill in the art that those patients with COPD whose symptoms are not well-controlled on LABA/LAMA/ICS would benefit from the treatment with an additional therapeutic. One would be motivated to not include patients who are well-controlled on the standard therapy of LABA/LAMA/ICS because the addition of another therapeutic is not necessary.
Regarding the administration route of claims 35, 37, 62-63, and 73-76, Orengo teaches a composition comprising an anti-IL-33 antibody that can be delivered subcutaneously with a needle and syringe, a pen delivery device, or an autoinjector delivery device [0215]. The methods are further directed toward administering a single initial dose of an IL-33 antibody, followed by one or more secondary doses [0231]. Although Orengo does not explicitly teach the subcutaneous administration of a composition of anti-IL-33 antibody alone (i.e. not in combination with another antibody), it would have been obvious to one of ordinary skill in the art that a method for the subcutaneous delivery of a composition comprising two antibodies could be applied to a composition comprised only of the anti-IL-33 antibody, because the method of a delivering a combination therapy could be easily adapted by the ordinary artisan and one would have a reasonable expectation of success.
Claims 1, 8, 15, 21, 23, 30, 35, 37, 52-53, 58-66, 68, and 70-82 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0155436 published June 7, 2018 (“Orengo”) in view of US 2015/0104447 published April 16, 2015 (“van der Merwe”; PTO-892 from 1/19/2024).
Orengo teaches a method for treating a subject with COPD who does not currently smoke with an IL-33 antibody. Orengo does not specifically teach a method of treating a subject with COPD with a blood eosinophil count greater than or equal to 300 cells/l or greater than or equal to 250 cells/l.
Van der Merwe teaches a method for treating a patient with COPD with a monoclonal antibody, benralizumab, which is an anti-IL-5 receptor antibody (see Abstract). In some embodiments, the patient has a blood eosinophil count of at least 200 cells/l, 300 cells/l, or 400 cells/l prior to administration of the COPD therapy [0009], as in instant claim 15 and 66.
Given that Orengo and van der Merwe are drawn to monoclonal antibody treatments of COPD and further given that van der Merwe discloses a patient population that could benefit from immunotherapy, it would have been obvious to one of ordinary skill in the art to use the antibody and method of Orengo in the patient population taught by van der Merwe (i.e. COPD patients with a certain eosinophil count), because van der Merwe has already identified this risk factor in patients with COPD. One would treat this patient population with the reasonable expectation that they would benefit from the anti-IL-33 antibody, as the antibody of Orengo has been shown to be effective in improving metrics of lung inflammation in a mouse model (Orengo, [0224]).
Response to Arguments
Applicant's arguments filed December 23, 2025 have been fully considered but they are not persuasive.
A. Orengo
I. Orengo does not teach or suggest all claim elements (pg 9-10)
Applicant asserts that Orengo does not teach the specific patient population and that Orengo only discloses a proposed study design for treating COPD patients that include current or former smokers (remarks, pg 9). Applicant states, “Orengo does not differentiate between current smokers and subjects who do not currently smoke”. However, it is the office’s position that Orengo does clearly distinguish these two patient populations. It would have been obvious to the ordinary artisan to select a former smoker with COPD to receive the anti-IL33 antibody therapy based on Orengo because Orengo teaches treatment of the genus smoker that is comprised of two species (i.e. current smoker and former smoker). Importantly, one claim of Patent ‘305 (the patent of Orengo) is directed to former smoker and one claim is directed to current smoker, revealing that Orengo had conceived of these two embodiments based on the disclosure that recited two species in the genus. Furthermore, when considering a prima facie case of obviousness, the prior art is presumed enabled; when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable (MPEP 2121.I). Based on the totality of the evidence, it is the examiner’s position that the disclosure of Orengo inherently supports and is enabling for a method of reducing annualized rate of AECOPD in subjects with COPD who no longer smoke with the anti-IL-33 antibody.
2. No reasonable expectation of success (pg 10-14)
Applicant argues that Orengo teaches away from using anti-IL-33 antibody monotherapy in inflammatory lung disease (remarks, pg 12), citing evidence in Orengo that combination therapy demonstrates superior efficacy than monotherapy. However, looking at Figures 3, 4B, 5, 6, 7A-B, and 8 of Orengo, monotherapy with REGN3500 (i.e. the claimed anti-IL-33 antibody) alone is effective to reduce various metrics of lung inflammation compared to IgG therapy alone. Applicant is reminded that absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. “Good science and useful contributions do not necessarily result in patentability.” PharmaStem Therapeutics, Inc. v. Viacell, Inc., 491 F.3d 1342 (Fed. Cir. 2007). The prior art as a whole suggests the desirability of a method for treating a former smoker with COPD with an anti-IL-33 antibody, thus providing a motivation to use the reference. This motivation need not be supported by a finding that the prior art suggested that the combination claimed by applicant was the preferred or most desirable combination over the other alternatives. It is the examiner’s position that the evidence of obviousness outweigh the case for unpredictability, since Orengo teaches the agent, the method, and the patient population. See, MPEP 716.02(c).II, which states: “Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness… In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990). Also, it is to be presumed that skilled workers would as matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the compenent worker. In re Michalek, 162 F.2d 229, 74 USPQ 107 (CCPA 1947); In re Reid, 179 F.2d 998, 84 USPQ478 (CCPA 1950).
Applicant asserts that the office mischaracterized the findings in OSI Pharm (pg 12-13), but arguments provided are not persuasive. The examiner finds that the specific facts and procedural posture of OSI Pharm do not apply to the instant claims. The claims under consideration in OSI Pharm are directed to method of treating NSCLC, a type of cancer, with erlotinib (remarks, pg 12). Because there was no efficacy data for erlotinib specific for NSCLC, the Court found that there is no basis for assuming the data pertain to NSCLC as opposed to other cancer (remarks, pg 12). In OSI Pharm, the distinction was made among different species of cancer; the ordinary artisan would appreciate that not all types of cancer are equivalents and are associated with different risk factors and causes, and a given treatment strategy that is effective for one condition will not necessarily extend to another condition. Because there was no in vitro or in vivo efficacy data regarding erlotinib and NSCLC, the Federal Circuit concluded that there was no substantial evidence to support a reasonable expectation of success (remarks, pg 12).
In comparison, Orengo recognizes that a treatment comprising the anti-IL-33 antibody could be broadly applied to various types of inflammatory disease and that the antibody can treat various diseases with similar characteristics. Specifically, Orengo teaches efficacy of anti-IL33 antibody monotherapy in the treatment of an inflammatory disease of the airway or lungs of a subject in the HDM exposed mouse model (Figures 2-4). Based on these findings, Orengo sets forth a method for treating COPD in smokers and former smokers. It would have been obvious to the ordinary artisan that a treatment to reduce lung inflammation in one disease (i.e. HDM exposed mouse model) would be applicable to other diseases associated with the same defect (i.e. COPD with lung inflammation); applying a known technique to a known disease ready for improvement will yield predictable results (see MPEP 2143).
3. Unexpected results
Applicant argues that Orengo does not teach reducing the annualized rate of AECOPD in the subject nor does it teach the subject with COPD that does not currently smoke (remarks, pg 15). While Orengo is silent on the intended results of the effect of the anti-IL-33 antibody on reduction in the annualized rate of AECOPD who were former smokers, it is clear that the same patient population treated with the same antibody would have the same characteristics and effects as the instantly claimed antibody since there is no evidence to the contrary. Note that rejections for anticipation are appropriate when the prior art discloses a method (or product) that appears to be identical except that the art is silent as to an inherent property; see MPEP § 2112(III). In such situations, the burden is on applicant to provide evidence that the prior art product (or method) is not the same. Subgroup analysis of a patient population does not require extensive or undue experimentation, and one of ordinary skill in the art would have a reasonable expectation of successfully identifying and treating COPD in a former smoker. Although applicant is correct that Orengo offers no teaching that the two groups would respond differently, the mere identification of the subgroup with improved efficacy is not sufficient evidence when considering a prima facie case of obviousness. Since Orengo teaches the method of treating COPD with the IL-33 antibody in both former and current smokers, the claimed method is obvious because the steps of the method are the same (i.e. selecting a smoker and administering the antibody). It is the examiner’s position that the evidence of obviousness outweigh the case for unpredictability, since Orengo teaches the agent, the method, and the patient population. The finding that combined analysis of a group comprising both current and former smokers failed to exhibit a statistically significant effect is not a sufficient argument, because Orengo implicitly teaches these two groups.
B. Orengo and van der Merwe
Applicant argues that the combination of Orengo in view of van de Merwe fails to disclose the method of reducing the annualized rate of AECOPD in a subject with COPD who no longer smokes with specific anti-IL-33 antibody (remarks, pg 16). The teachings of Orengo have been discussed above. Although applicant is correct that the van de Merwe reference says nothing about an anti-IL-33 antibody for the treatment of COPD in a former smoker, it is not necessary for this secondary reference to contain all the limitations of the presently claimed method. The rejection in view of van de Merwe was established based on the teachings therein regarding identification of a population of patients with COPD with elevated blood eosinophil count who may benefit from immunotherapy. As such, it is the combination of references that render the claims rejected under 103 obvious. One looking to treat patients with COPD would apply a known metric of disease state when selecting a patient of specific disease severity. In response to applicant’ arguments against the references individually, 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). Applicant’s arguments do not show how the combined teachings of the cited references and the knowledge/skills contained therein cannot render the rejected claims obvious.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675