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 .
Reopening of Prosecution after Appeal Brief
In view of the appeal brief filed on August 6, 2026, PROSECUTION IS HEREBY REOPENED. A new ground of rejection is set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on February 23, 2026 and March 26, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
Withdrawn Rejections
Applicant’s arguments filed August 6, 2026 regarding the rejections of the claims under 35 U.S.C. 103 over Orengo and over Orengo in view of van der Mewe have been fully considered and are persuasive. There is no teaching or suggestion in Orengo that the former smoker with COPD would be more responsive to the anti-IL-33 antibody therapy than current smokers with COPD. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made over Orengo in view of Bhatt et al.
New 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) in view of Bhatt et al, published January 2019 (see instant PTO-892).
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 of 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 not to 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.
To the extent that Orengo does not explicitly identify the former smoker with COPD as a population to select because of an enhanced response to anti-IL33 antibody therapy, Bhatt teaches that smoking status of COPD patients affects responsiveness to anti-inflammatory therapy (pg 1). Specifically, Bhatt teaches that former smokers respond better to anti-inflammatory inhaled corticosteroid (ICS) therapy than continuing and intermittent smokers with COPD (pg 1-2). Compared with placebo, the adjusted mean change in forced expiratory volume in 1 s (FEV1) at 3, 6, 9, and 12 months was greater in former smokers than in current smokers (see Figure 1). Also, former smokers had greater reduction in percentage rates of moderate or severe exacerbations with ICS/LABA compared to current smokers (pg 2). Bhatt et al teaches that this reduction in response in current smokers may be due to the pro-inflammatory effects of cigarette smoke, which is well described (pg 2).
Based on the combined teachings of Orengo and Bhatt et al, it would have been obvious to one of ordinary skill in the art at the time the invention was filed to administer the claimed anti-IL-33 antibody to a COPD subject who is a former smoker, as taught by Orengo, especially in view of the teachings of Bhatt et al that former smokers exhibit a better response to anti-inflammatory therapy than current smokers. Orengo teaches that IL-33 is a proinflammatory cytokine released by damaged epithelial tissue in response to insults such as allergens, viruses, or smoke [0005]; an inhibitor of IL-33, such as the anti-IL33 antibody claimed, would be expected to decrease inflammation. Thus, a person of ordinary skill in the art would have had reason to employ the known anti-IL-33 antibody COPD therapy of Orengo in the former smoker population because Bhatt et al identifies former smokers as a population that responds more favorably to anti-inflammatory treatment. The combination of references would have provided a known COPD treatment (i.e. the anti-IL33 antibody) to a patient population (i.e. former smokers with COPD) identified in the prior art as being more responsive to anti-inflammatory therapy.
Further, one of ordinary skill in the art would have had a reasonable expectation of success in treating COPD in a former smoker with the anti-IL-33 antibody. Orengo expressly teaches treatment of COPD in former smoker using anti-IL-33 antibody. Thus, the claimed treatment does not require development of a new therapeutic agent or an unpredictable application of the antibody, but rather the method involves administration of the known antibody to the same patient population for the same disease as expressly taught by Orengo. The teachings of Bhatt et al support the expectation that a former smoker would respond to an anti-inflammatory COPD therapy and provide the motivation to modify the method of Orengo to arrive at the claimed invention. Such amounts to the combining of prior art elements according to know methods to yield predictable results, see MPEP 2143.
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 of Bhatt et al, published January 2019 , as applied to claims 1, 8, 21, 23, 30, 35, 37, 52-53, 58-65, 68, and 70-82 above, and further in view of US 2015/0104447 published April 16, 2015 (“van der Merwe”; PTO-892 from 1/19/2024).
Orengo in view of Bhatt et al 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 in view of Bhatt et al 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]).
Conclusion
No claim is allowed.
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).
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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.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
