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 .
Applicant's response to the previous Office action, dated March 18, 2026, has been received. By way of this submission, Applicant has amended claims 1, 2, 17, 19, and 49, and introduced new claims 82-84.
Claims 1-2, 17, 19, 40-41, 43-44, 49, 80, and 82-84 are pending in the application. Claims 43-44 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed March 31, 2021.
Claims 1-2, 17, 19, 40-41 49, 80, and 82-84 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated December 17, 2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 18, 2026 was filed after the mailing date of the first Office action on the merits on May 5, 2021. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 17, 19, 40-41, 49, 80, and 82-84 are rejected under 35 U.S.C. 103 as being unpatentable over Orengo (US20180155436A1) in view of Ardeleanu (US20140056920A1) and
Matsumoto (Allergol Int. 2014 Jun;63(2):153-60).
Applicant argues that the references do not teach every aspect of the claims as amended; specifically, Orengo, Ardeleanu, and Matsumoto do not teach a method of treating asthma. Applicant asserts that the example cited in Orengo is directed to evaluation of patients with COPD, and not asthma, and that Orengo does not provide any results concerning FEV1 or pre-bronchodilator FEV1 when a subject with asthma is administered the claimed antibodies. Applicant further argues that Orengo does not teach the claimed dosing regimen, nor does Orengo teach or disclose administering the claimed antibodies to an adult subject who has asthma, a blood eosinophil count of greater than 300 cells/µL, and a blood periostin level of ≥74.4 ng/mL, or that doing so would improve FEV1 in the subject. For these reasons, one of ordinary skill would not have any reasonable expectation of success in arriving at the claimed invention based upon the teachings of Orengo, Ardeleanu, and Matsumoto.
Applicant's arguments have been considered fully but are not found to be persuasive.
Applicant has traversed the primary and the secondary references pointing to the differences between the claims and the disclosure in each reference. Applicant is respectfully reminded that the rejection is under 35 U.S.C. 103 and that non-obviousness cannot be established by attacking the references individually when the rejection is based on the combination of the references. In re Keller, 642 F.2d 4B, 208 USPQ 871, 882 (CCPA 1981) and MPEP 2145(IV). This Applicant has not done, but rather argues the references individually and not their combination. One cannot show non-obviousness by attacking references individually where the rejections are based on a combination of references.
Contrary to Applicant's assertions, Orengo teaches methods for treating an inflammatory disease, comprising administering to a subject in need thereof one or more doses of a therapeutically effective amount of an interleukin-33 (IL-33) antagonist in combination with one or more doses of a therapeutically effective amount of an interleukin-4 receptor (IL-4R) antagonist (claim 1), and that the inflammatory disease may be eosinophilic asthma (claims 3 and 6). Orengo further teaches dosages of the IL-33 and IL-4R antagonist of 300 mg (para. 0221).
Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")). MPEP 2143.02.
Orengo also states that the examples recited are not intended to limit the scope of what the inventors regard as their invention (para. 0237).
Additionally, Ardeleanu teaches that administration of an IL-4R antagonist may improve FEV1 (para. 0010, 0073-0075 and Figure 2). Ardeleanu also teaches treatment of asthma (para. 0002).
Ardeleanu at para. 0010: "In various embodiments, methods for improving one or more asthma-associated parameters comprise administering to a subject in need thereof, a therapeutically effective amount of an IL-4R antagonist, wherein the improvement in an asthma-associated parameter is defined as one of the following: an increase from baseline of FEV1..."
Ardeleanu further teaches that patients with eosinophilic asthma may have blood eosinophils greater than or equal to 300 cells/µL (para. 0013).
Ardeleanu further teaches that periostin levels are found to be upregulated in patients with asthma, and that IL-4R antagonists are useful in treating patients with elevated levels of periostin (para. 0158).
Matsumoto teaches that serum periostin is a strong predictor of airway eosinophilia in patients with severe asthma who remain symptomatic despite maximal ICS treatment (page 154, right column, second paragraph). Matsumoto further teaches that a population of patients with asthma and an average age of 62.3 years had an average serum periostin level of 92.8 ng/mL, compared to a population of healthy subjects with an average serum periostin level of 39.1 ng/mL (page 154, right column, fourth and fifth paragraphs).
The teachings of Ardeleanu and Matsumoto make it clear that a patient with eosinophilic asthma may have a blood eosinophil count of greater than 300 cells/µL and a blood periostin level of >74.4 ng/mL. From there, one of ordinary skill would apply a known treatment for eosinophilic asthma, such as the method taught by Orengo.
Furthermore, Orengo teaches that the subject may have moderate-to-severe asthma that is not well controlled on inhaled corticosteroid (ICS) plus long-acting β2 adrenergic agonist (LABA) therapy (para. 0334), which is pertinent to new claim 82.
Orengo further teaches that the IL-4R antagonist may be dupilumab, and the IL-33 antagonist may be REGN3500, which is the same as SAR440340 (claim 28), which is pertinent to new claim 83.
Orengo further teaches the use of an autoinjector (para. 0216), which is pertinent to new claim 84.
This rejection is therefore maintained and extended to encompass new claims 82-84.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 17, 19, 40-41, 49-51, 80, and 82-84 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 9, 20-21, 25, 32, 37 and 44-45 of copending Application No. 17/786,226 in view of Ardeleanu and Matsumoto.
Applicant argues that the '226 application does not constitute a proper doble patenting rejection, as the '226 application, upon allowance, would not extend the life of a patent from the instant application.
Applicant's arguments have been considered fully but are not found to be persuasive.
If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent. MPEP 804(I)(A)(1)(b)(i). As the claims are not in condition for allowance, this rejection must be maintained. This rejection will be reconsidered when there is allowable subject matter indicted.
Futhermore, Ardeleanu teaches that the background therapy may comprise an inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA) (para. 0015), which is pertinent to new claim 82.
The '226 application claims that the antibodies may be dupilumab (claim 21 and 96), and the antibodies of the '226 application have identical complementarity determining regions to those of SAR440340, which is pertinent to new claim 83.
The '226 application claims that the antibodies in question may be administered with an autoinjector (claim 25 and 97), which is pertinent to new claim 84.
This rejection is therefore maintained and extended to encompass new claims 82-84.
Claims 1-2, 17, 19, 40-41, 49-51, 80, and 82-84 are rejected on the ground of nonstatutory double patenting as being unpatentable overclaims 1-44 of U.S. Patent No. 10,815,305 in view of Ardeleanu, Matsumoto and Clinical Trial NCT03387852 (cited previously).
Applicant argues that the claims of the '305 patent do not recite improving FEV1 or pre-bronchodilator FEV in the subject in need thereof upon administration of an IL-33 antagonist in combination with an IL-4R antagonist, nor the claimed dosage, or the claimed criteria for selection of the patient population.
Applicant's arguments have been considered fully but are not found to be persuasive.
Ardeleanu teaches that administration of an IL-4R antagonist may improve FEV1 (para. 0010, 0073-0075 and Figure 2). Ardeleanu also teaches treatment of asthma (para. 0002).
Ardeleanu further teaches dosages of an IL-4R antagonist of 300 mg (para. 0139). Ardeleanu also teaches maintenance doses (para. 0147).
Ardeleanu further teaches that patients with eosinophilic asthma may have blood eosinophils greater than or equal to 300 cells/µL (para. 0013).
Ardeleanu further teaches that periostin levels are found to be upregulated in patients with asthma, and that IL-4R antagonists are useful in treating patients with elevated levels of periostin (para. 0158).
Matsumoto teaches that serum periostin is a strong predictor of airway eosinophilia in patients with severe asthma who remain symptomatic despite maximal ICS treatment (page 154, right column, second paragraph). Matsumoto further teaches that a population of patients with asthma and an average age of 62.3 years had an average serum periostin level of 92.8 ng/mL, compared to a population of healthy subjects with an average serum periostin level of 39.1 ng/mL (page 154, right column, fourth and fifth paragraphs).
The teachings of Ardeleanu and Matsumoto make it clear that a patient with eosinophilic asthma may have a blood eosinophil count of greater than 300 cells/µL and a blood periostin level of >74.4 ng/mL.
While the cited references do not explicitly teach the claimed dosage of the IL-33-binding antibody, determination of dosage is routinely determined by the ordinary artisan as of the effective filing date of the claimed invention, and was known as a result effective variable that depends on the conditions of the patients. It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious). One of ordinary skill in the art would appreciate the amount or dosage of the antibody in the therapy could be adjusted to achieve optimum therapeutic efficacy. Applicant has not presented evidence of any unexpected criticality of the claimed dosage schedule. Also see Ardeleanu at para. 0129: "Effective dosages and schedules for administering pharmaceutical compositions comprising anti-IL-4R antibodies may be determined empirically; for example, patient progress can be monitored by periodic assessment, and the dose adjusted accordingly."
Furthermore, Clinical Trial NCT03387852 teaches that the antibodies in question may be REGN3500 (i.e., SAR440340) and dupilumab (page 3), which is pertinent to new claim 83.
Ardeleanu teaches that the background therapy may comprise an inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA) (para. 0015), which is pertinent to new claim 82.
Ardeleanu teaches that the compositions in question may be administered with an autoinjector (para. 0132), which is pertinent to new claim 84.
This rejection is therefore maintained and extended to encompass new claims 82-84.
Claims 1-2, 17, 19, 40-41, 49-51, 80, and 82-84 are rejected on the ground of nonstatutory double patenting as being unpatentable overclaims 1-44 of U.S. Patent No. 11,866,503 in view of Ardeleanu, Matsumoto and Clinical Trial NCT03387852 (cited previously).
Applicant argues that the claims of the '503 patent do not recite improving FEV1 or pre-bronchodilator FEV in the subject in need thereof upon administration of an IL-33 antagonist in combination with an IL-4R antagonist, nor the claimed dosage, or the claimed criteria for selection of the patient population.
Applicant's arguments have been considered fully but are not found to be persuasive.
Ardeleanu teaches that administration of an IL-4R antagonist may improve FEV1 (para. 0010, 0073-0075 and Figure 2). Ardeleanu also teaches treatment of asthma (para. 0002).
Ardeleanu further teaches dosages of an IL-4R antagonist of 300 mg (para. 0139). Ardeleanu also teaches maintenance doses (para. 0147).
Ardeleanu further teaches that patients with eosinophilic asthma may have blood eosinophils greater than or equal to 300 cells/µL (para. 0013).
Ardeleanu further teaches that periostin levels are found to be upregulated in patients with asthma, and that IL-4R antagonists are useful in treating patients with elevated levels of periostin (para. 0158).
Matsumoto teaches that serum periostin is a strong predictor of airway eosinophilia in patients with severe asthma who remain symptomatic despite maximal ICS treatment (page 154, right column, second paragraph). Matsumoto further teaches that a population of patients with asthma and an average age of 62.3 years had an average serum periostin level of 92.8 ng/mL, compared to a population of healthy subjects with an average serum periostin level of 39.1 ng/mL (page 154, right column, fourth and fifth paragraphs).
The teachings of Ardeleanu and Matsumoto make it clear that a patient with eosinophilic asthma may have a blood eosinophil count of greater than 300 cells/µL and a blood periostin level of >74.4 ng/mL.
While the cited references do not explicitly teach the claimed dosage of the IL-33-binding antibody, determination of dosage is routinely determined by the ordinary artisan as of the effective filing date of the claimed invention, and was known as a result effective variable that depends on the conditions of the patients. It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious). One of ordinary skill in the art would appreciate the amount or dosage of the antibody in the therapy could be adjusted to achieve optimum therapeutic efficacy. Applicant has not presented evidence of any unexpected criticality of the claimed dosage schedule. Also see Ardeleanu at para. 0129: "Effective dosages and schedules for administering pharmaceutical compositions comprising anti-IL-4R antibodies may be determined empirically; for example, patient progress can be monitored by periodic assessment, and the dose adjusted accordingly."
Furthermore, Clinical Trial NCT03387852 teaches that the antibodies in question may be REGN3500 (i.e., SAR440340) and dupilumab (page 3), which is pertinent to claim 83.
Ardeleanu teaches that the background therapy may comprise an inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA) (para. 0015), which is pertinent to claim 82.
Ardeleanu teaches that the compositions in question may be administered with an autoinjector (para. 0132), which is pertinent to new claim 84.
This rejection is therefore maintained and extended to encompass new claims 82-84.
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.
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/PETER JOHANSEN/Examiner, Art Unit 1644
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