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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/13/2026 has been entered.
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.
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 1-3, 5, 7-9, 21-22, 25-27, 30-33, and 35-46 are rejected under 35 U.S.C. 103 as being unpatentable over Orengo et al, (WO2018118713A1, of record), hereinafter Orengo, in view of Agache et al (Agache, I et al. “In vivo diagnosis of allergic diseases--allergen provocation tests.” Allergy vol. 70,4 (2015): 355-65. doi:10.1111/all.12586, of record), hereinafter Agache, and Gherasim et al (Gherasim, Alina, et al. "Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC® environmental exposure chamber." Clinical & Experimental Allergy 50.2 (2020): 160-169, of record), hereinafter Gherasim.
Orengo discloses a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering a pharmaceutical composition containing one or more Fel-d1-specific monoclonal antibodies or antigen-binding fragments to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein, wherein one Fel-d1-specific antibody comprises VH and VL chains of SEQ ID NOs: 18 and 26, respectively and the other Fel-d1-specific antibody comprises VH and VL chains of SEQ ID NOs: 306 and 314, respectively (see entire document, in particular, Abstract, Summary of the Invention, Claims, Para. 0120, Para. 0123, Para. 0126). The VH and VL chains of SEQ ID NOs: 18 and 26 correspond to SEQ ID NOs: 18 and 26 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30 and 32. The VH and VL chains of SEQ ID NOs: 306 and 314 correspond to SEQ ID NOs: 306 and 314 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 308, 310, 312, 316, 318, and 320. The Fel-d1 antibodies can also prevent even more serious in vivo complications associated with exposure to Fel-d1 in a sensitized individual, such as asthmatic responses, anaphylaxis, or even death (Para. 0011). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The therapeutic compositions comprising the Fel-d1 antibodies or antigen-binding fragments can be administered subcutaneously, intravenously, or intranasally, wherein each antibody is given at a single dose or at an initial dose of about 1 to about 600 mg (e.g. 300 mg each) and subsequent doses separated by at least 8 weeks, 10, weeks, 12 weeks or 14 weeks (Para. 0141-0144 and Para. 0280-0281). One or more Fel-d1 antibodies (antibody combination) can be administered sequentially in a single initial dose and then at one or more subsequent doses (Para. 0299). The additional Fel-d1 antibodies can be administered prior to, concurrent with, or after the administration of an anti-Fel dl antibody disclosed (Para. 0153-0154 and Para. 0297-0298). If the second Fel-d1 antibody is administered prior to or after the administration of the first Fel-d1 antibody, then the antibodies are necessarily formulated individually and administered sequentially. The Fel-d1 antibodies provided in a single dose of an antibody combination would necessarily be co-formulated and administered concurrently. Specifically, it was shown that a single subcutaneous dose of REGN1908-1909 (a combination of Fel-d1 specific antibodies H4H1232N and H4H2636P presently recited in the claims) (600 mg total, 1:1 antibody ratio) administered to human subjects having cat-induced allergic rhinitis and sensitization at screening but not currently living with a cat blocked the early allergic response to nasal challenge with cat hair extract and led to a clinically meaningful and sustained reduction in total nasal symptoms. Thus, it was concluded that the Fel-d1 specific antibodies can prevent allergen-induced allergic response (Example 11, Patient Population under Para. 0384, and Figure 8).
Orengo does not specifically teach that the patient has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3. Further, it is not taught that the subject has GINA stage 1 asthma.
However, Agache teaches that allergen challenge tests are established diagnostic tools for allergic disease, providing direct proof of the clinical relevance of a particular allergen (Abstract). In particular, Agache describes the bronchial allergen provocation test in which airway hyper-reactivity (AHR) is assessed by measuring decreases in FEV1 following allergen inhalation. A positive early airway response (EAR) is defined by a ≥ 20% fall in FEV1 from baseline, typically occurring within 30 minutes and resolving within 3 hours, with the EAR quantifiable as the area under the curve of percentage FEV1 decrease over the first 2 hours after challenge (“Bronchial allergen provocation test” section, in particular, “Rationale and Indications” as well as “Procedure” subsections). Thus, Agache teaches that a ≥ 20% fall in FEV1 within 2 hours of allergen challenge is a diagnostic indicator of allergy to that allergen.
Gherasim further teaches that in a house with a cat, it takes approximately 40 minutes for a cat-allergic person to develop asthma symptoms. In an environment exposure chamber (EEC), with a nebulized Fel d 1 concentration of 40 ng/m3 and with 10 L of ventilation per minute, the cumulative inhaled dose of Fel d 1 will be 16 ng in 40 minutes and can elicit an early asthmatic response (EAR) defined as a 20% drop in forced expiratory volume over 1 second (FEV1) during 2 hours of exposure . Thus, the exposure to cat allergen in the EEC corresponds to the natural exposure in terms of the cumulative Fel d 1 dose (Discussion, 2nd Paragraph and Section 2.1). Specifically, it is taught that cat-asthmatic patients with GINA 1 asthma (controlled intermittent asthma requiring step 1 treatment – short acting beta 2 agonists- as needed) are exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in the EEC and exited the EEC as soon as a 20% drop in FEV1 was observed (Abstract and Sections 2.1-2.4). As such, cat asthmatic patients with GINA 1 asthma represent a patient population that would receive therapeutic benefit from treatment with anti-allergy agents.
It would have been obvious to one of ordinary skill in the art to modify the method of Orengo such that the patient selected for treatment with the anti-Fel d1 antibodies has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3. One of ordinary skill in the art would have been motivated to do so since Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR useful for diagnosing allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an early asthmatic response under exposure conditions modelling real-world patient environments. Further, it would have been obvious to apply the method of Orengo to cat-allergic patients having GINA 1 asthma disclosed by Gherasim since they represent a patient population that would receive therapeutic benefit from anti-Fel d 1 treatment. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) to greater than 4 hours or decreases the incidence of EAR by about 20% relative to placebo when measured at day 8, 29, or 57 after administration. As such, the method taught by the combined teachings of the prior art having the same minimally required active steps and Fel-d1 specific antibodies of the instant claims necessarily yield the same intended results. Therefore, one of ordinary skill in the art would expect that administration of the recited Fel-d1 antibodies can effectively treat cat-allergic subjects who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 – including those not living with a cat or having GINA 1 asthma.
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 1-3, 5, 7-9, 21-22, 25-27, 30-33, and 35-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11352417B2 in view of Orengo et al, (WO2018118713A1, of record), hereinafter Orengo, and Agache et al (Agache, I et al. “In vivo diagnosis of allergic diseases--allergen provocation tests.” Allergy vol. 70,4 (2015): 355-65. doi:10.1111/all.12586, of record), hereinafter Agache, and Gherasim et al (Gherasim, Alina, et al. "Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC® environmental exposure chamber." Clinical & Experimental Allergy 50.2 (2020): 160-169, of record), hereinafter Gherasim.
The issued claims recite a method for reducing the severity, duration or frequency of occurrence of one or more symptoms of an allergic response to Fel-d1 in a subject comprising administering two Fel-d1 specific monoclonal antibodies or antigen binding fragments to the subject, wherein the first and second antibodies have a VH/VL chain pair of SEQ ID NOs: 18/26 and 306/314, respectively, and are administered as a single subcutaneous dose of 600 mg (300 mg of each antibody), wherein treatment results in at least a 20% reduction from baseline in at least one patient reported outcome score 8 days after the single subcutaneous dose (issued claim 1). The VH/VL chain pair of SEQ ID NOs: 18/26 correspond to SEQ ID NOs: 18/26 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30 and 32. The VH/VL chain pair of SEQ ID NOs: 306/314 correspond to SEQ ID NOs: 306/314 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 308, 310, 312, 316, 318, and 320. Since the two Fel-d1 specific antibodies are provided to the subject as a single dose, the antibodies are necessarily co-formulated and administered concurrently.
The issued claims do not recite that 1) the subject has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3, 2) the subject having an allergy to a cat has asthma or does not live with a cat, 3) the subject has GINA stage 1 asthma, and 4) routes of administration, frequency of administration of more than one dosage, or dosage amounts.
However, Orengo discloses a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering a pharmaceutical composition containing one or more Fel-d1-specific monoclonal antibodies or antigen-binding fragments of the issued claims to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein (see entire document, in particular, Abstract, Summary of the Invention, Claims, Para. 0120, Para. 0123, Para. 0126). The Fel-d1 antibodies can also prevent even more serious in vivo complications associated with exposure to Fel-d1 in a sensitized individual, such as asthmatic responses, anaphylaxis, or even death (Para. 0011). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The therapeutic compositions comprising the Fel-d1 antibodies or antigen-binding fragments can be administered at an initial dose of about 1 to about 600 mg (e.g. 300 mg each) and subsequent doses separated by at least 8 weeks, 10, weeks, 12 weeks or 14 weeks (Para. 0141-0144 and Para. 0280-0281). One or more Fel-d1 antibodies (antibody combination) can be administered sequentially in a single initial dose and then at one or more subsequent doses (Para. 0299). The additional Fel-d1 antibodies can be administered prior to, concurrent with, or after the administration of an anti-Fel dl antibody disclosed (Para. 0153-0154 and Para. 0297-0298). If the second Fel-d1 antibody is administered prior to or after the administration of the first Fel-d1 antibody, then the antibodies are necessarily formulated individually and administered sequentially. Specifically, it was shown that a single subcutaneous dose of REGN1908-1909 (a combination of Fel-d1 specific antibodies H4H1232N and H4H2636P presently recited in the instant and issued claims) (600 mg total, 1:1 antibody ratio) administered to human subjects having cat-induced allergic rhinitis and sensitization at screening but not currently living with a cat blocked the early allergic response to nasal challenge with cat hair extract and led to a clinically meaningful and sustained reduction in total nasal symptoms. Thus, the Fel-d1 specific antibodies can prevent allergen-induced allergic response (Example 11, Patient Population under Para. 0384, and Figure 8).
Agache further teaches that allergen challenge tests are established diagnostic tools for allergic disease, providing direct proof of the clinical relevance of a particular allergen (Abstract). In particular, Agache describes the bronchial allergen provocation test in which airway hyper-reactivity (AHR) is assessed by measuring decreases in FEV1 following allergen inhalation. A positive early airway response (EAR) is defined by a ≥ 20% fall in FEV1 from baseline, typically occurring within 30 minutes and resolving within 3 hours, with the EAR quantifiable as the area under the curve of percentage FEV1 decrease over the first 2 hours after challenge (“Bronchial allergen provocation test” section, in particular, “Rationale and Indications” as well as “Procedure” subsections). Thus, Agache teaches that a ≥ 20% fall in FEV1 within 2 hours of allergen challenge is a diagnostic indicator of allergy to that allergen.
Gherasim further teaches that in a house with a cat, it takes approximately 40 minutes for a cat-allergic person to develop asthma symptoms. In an environment exposure chamber (EEC), with a nebulized Fel d 1 concentration of 40 ng/m3 and with 10 L of ventilation per minute, the cumulative inhaled dose of Fel d 1 will be 16 ng in 40 minutes and can elicit an early asthmatic response (EAR) defined as a 20% drop in forced expiratory volume over 1 second (FEV1) during 2 hours of exposure . Thus, the exposure to cat allergen in the EEC corresponds to the natural exposure in terms of the cumulative Fel d 1 dose (Discussion, 2nd Paragraph and Section 2.1). Specifically, it is taught that cat-asthmatic patients with GINA 1 asthma (controlled intermittent asthma requiring step 1 treatment – short acting beta 2 agonists- as needed) are exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in the EEC and exited the EEC as soon as a 20% drop in FEV1 was observed (Abstract and Sections 2.1-2.4). As such, cat asthmatic patients with GINA 1 asthma represent a patient population that would receive therapeutic benefit from treatment with anti-allergy agents.
It would have been obvious to one of ordinary skill in the art to modify the method of the issued claims such that the Fel-d1 specific antibodies are administered to cat-allergic subjects – including those not living with a cat as taught by Orengo –who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 as taught by Agache and Gherasim. One of ordinary skill in the art would have been motivated to do so since Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR useful for diagnosing allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an EAR under exposure conditions modelling real-world patient environments. Orengo further teaches that Fel d 1 antibodies reduce allergic rhinitis or allergic asthma in cat-allergic subjects – including those not living with a cat – and provides suitable routes, dosages, and frequencies of administration for the Fel d 1 antibodies. Additionally, it would have been obvious to apply the method of issued claims to cat-allergic patients having GINA 1 asthma disclosed by Gherasim since they represent a patient population that would receive therapeutic benefit from anti-Fel d 1 treatment. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) to greater than 4 hours or decreases the incidence of EAR by about 20% relative to placebo when measured at day 8, 29, or 57 after administration. As such, the method taught by the combined teachings of the issued claims and prior art, having the same minimally required active steps and Fel-d1 specific antibodies of the instant claims, necessarily yield the same intended results. Therefore, one of ordinary skill in the art would expect that administration of the recited Fel-d1 antibodies can effectively treat cat-allergic subjects who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 – including those not living with a cat or having GINA 1 asthma.
Claims 1-3, 5, 7-9, 21-22, 25-27, 30-33, and 35-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9475869B2 in view of Orengo et al, (WO2018118713A1, of record), hereinafter Orengo, and Agache et al (Agache, I et al. “In vivo diagnosis of allergic diseases--allergen provocation tests.” Allergy vol. 70,4 (2015): 355-65. doi:10.1111/all.12586, of record), hereinafter Agache, and Gherasim et al (Gherasim, Alina, et al. "Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC® environmental exposure chamber." Clinical & Experimental Allergy 50.2 (2020): 160-169, of record), hereinafter Gherasim.
The issued claims recite a method of treating a patient having sensitivity to or an allergic reaction against a cat, cat dander, cat hair or an extract thereof, or to Fel-d1 protein, comprising administering one or more Fel-d1 specific monoclonal antibodies having the VH/VL chain pairs of SEQ ID NOs: 18/26 and 306/314 in order to reduce the sensitivity or frequency and/or duration of the allergic reaction (issued claim 1). The VH/VL chain pair of SEQ ID NOs: 18/26 correspond to SEQ ID NOs: 18/26 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30 and 32. The VH/VL chain pair of SEQ ID NOs: 306/314 correspond to SEQ ID NOs: 306/314 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 308, 310, 312, 316, 318, and 320.
The issued claims do not recite that 1) the subject has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3, 2) the subject having an allergy to a cat has asthma or does not live with a cat, 3) the subject has GINA stage 1 asthma, and 4) routes of administration, frequency of administration of more than one dosage, or dosage amounts.
However, Orengo discloses a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering a pharmaceutical composition containing one or more Fel-d1-specific monoclonal antibodies or antigen-binding fragments of the issued claims to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein (see entire document, in particular, Abstract, Summary of the Invention, Claims, Para. 0120, Para. 0123, Para. 0126). The Fel-d1 antibodies can also prevent even more serious in vivo complications associated with exposure to Fel-d1 in a sensitized individual, such as asthmatic responses, anaphylaxis, or even death (Para. 0011). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The therapeutic compositions comprising the Fel-d1 antibodies or antigen-binding fragments can be administered at an initial dose of about 1 to about 600 mg (e.g. 300 mg each) and subsequent doses separated by at least 8 weeks, 10, weeks, 12 weeks or 14 weeks (Para. 0141-0144 and Para. 0280-0281). One or more Fel-d1 antibodies (antibody combination) can be administered sequentially in a single initial dose and then at one or more subsequent doses (Para. 0299). The additional Fel-d1 antibodies can be administered prior to, concurrent with, or after the administration of an anti-Fel dl antibody disclosed (Para. 0153-0154 and Para. 0297-0298). If the second Fel-d1 antibody is administered prior to or after the administration of the first Fel-d1 antibody, then the antibodies are necessarily formulated individually and administered sequentially. Specifically, it was shown that a single subcutaneous dose of REGN1908-1909 (a combination of Fel-d1 specific antibodies H4H1232N and H4H2636P presently recited in the instant and issued claims) (600 mg total, 1:1 antibody ratio) administered to human subjects having cat-induced allergic rhinitis and sensitization at screening but not currently living with a cat blocked the early allergic response to nasal challenge with cat hair extract and led to a clinically meaningful and sustained reduction in total nasal symptoms. Thus, the Fel-d1 specific antibodies can prevent allergen-induced allergic response (Example 11, Patient Population under Para. 0384, and Figure 8).
Agache further teaches that allergen challenge tests are established diagnostic tools for allergic disease, providing direct proof of the clinical relevance of a particular allergen (Abstract). In particular, Agache describes the bronchial allergen provocation test in which airway hyper-reactivity (AHR) is assessed by measuring decreases in FEV1 following allergen inhalation. A positive early airway response (EAR) is defined by a ≥ 20% fall in FEV1 from baseline, typically occurring within 30 minutes and resolving within 3 hours, with the EAR quantifiable as the area under the curve of percentage FEV1 decrease over the first 2 hours after challenge (“Bronchial allergen provocation test” section, in particular, “Rationale and Indications” as well as “Procedure” subsections). Thus, Agache teaches that a ≥ 20% fall in FEV1 within 2 hours of allergen challenge is a diagnostic indicator of allergy to that allergen.
Gherasim further teaches that in a house with a cat, it takes approximately 40 minutes for a cat-allergic person to develop asthma symptoms. In an environment exposure chamber (EEC), with a nebulized Fel d 1 concentration of 40 ng/m3 and with 10 L of ventilation per minute, the cumulative inhaled dose of Fel d 1 will be 16 ng in 40 minutes and can elicit an early asthmatic response (EAR) defined as a 20% drop in forced expiratory volume over 1 second (FEV1) during 2 hours of exposure . Thus, the exposure to cat allergen in the EEC corresponds to the natural exposure in terms of the cumulative Fel d 1 dose (Discussion, 2nd Paragraph and Section 2.1). Specifically, it is taught that cat-asthmatic patients with GINA 1 asthma (controlled intermittent asthma requiring step 1 treatment – short acting beta 2 agonists- as needed) are exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in the EEC and exited the EEC as soon as a 20% drop in FEV1 was observed (Abstract and Sections 2.1-2.4). As such, cat asthmatic patients with GINA 1 asthma represent a patient population that would receive therapeutic benefit from treatment with anti-allergy agents.
It would have been obvious to one of ordinary skill in the art to modify the method of the issued claims such that the Fel-d1 specific antibodies are administered to cat-allergic subjects – including those not living with a cat as taught by Orengo –who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 as taught by Agache and Gherasim. One of ordinary skill in the art would have been motivated to do so since Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR useful for diagnosing allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an EAR under exposure conditions modelling real-world patient environments. Orengo further teaches that Fel d 1 antibodies reduce allergic rhinitis or allergic asthma in cat-allergic subjects – including those not living with a cat – and provides suitable routes, dosages, and frequencies of administration for the Fel d 1 antibodies. Additionally, it would have been obvious to apply the method of issued claims to cat-allergic patients having GINA 1 asthma disclosed by Gherasim since they represent a patient population that would receive therapeutic benefit from anti-Fel d 1 treatment. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) to greater than 4 hours or decreases the incidence of EAR by about 20% relative to placebo when measured at day 8, 29, or 57 after administration. As such, the method taught by the combined teachings of the issued claims and prior art, having the same minimally required active steps and Fel-d1 specific antibodies of the instant claims, necessarily yield the same intended results. Therefore, one of ordinary skill in the art would expect that administration of the recited Fel-d1 antibodies can effectively treat cat-allergic subjects who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 – including those not living with a cat or having GINA 1 asthma.
Claims 1-3, 5, 7-9, 21-22, 25-27, 30-33, and 35-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 10047153B2 in view of Orengo et al, (WO2018118713A1, of record), hereinafter Orengo, and Agache et al (Agache, I et al. “In vivo diagnosis of allergic diseases--allergen provocation tests.” Allergy vol. 70,4 (2015): 355-65. doi:10.1111/all.12586, of record), hereinafter Agache, and Gherasim et al (Gherasim, Alina, et al. "Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC® environmental exposure chamber." Clinical & Experimental Allergy 50.2 (2020): 160-169, of record), hereinafter Gherasim.
The issued claims recite a method of treating a patient having sensitivity to or an allergic reaction against a cat, cat dander, cat hair or an extract thereof, or to Fel-d1 protein, comprising administering one or more Fel-d1 specific monoclonal antibodies having the VH/VL chain pairs of SEQ ID NOs: 18/26 and 306/314, wherein treatment results in a reduction in allergic rhinitis or allergic asthma (issued claim 1, 29, and 32). The VH/VL chain pair of SEQ ID NOs: 18/26 correspond to SEQ ID NOs: 18/26 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30 and 32. The VH/VL chain pair of SEQ ID NOs: 306/314 correspond to SEQ ID NOs: 306/314 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 308, 310, 312, 316, 318, and 320.
The issued claims do not recite that 1) the subject has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3, 2) the subject having an allergy to a cat has asthma or does not live with a cat, 3) the subject has GINA stage 1 asthma, and 4) routes of administration, frequency of administration of more than one dosage, or dosage amounts.
However, Orengo discloses a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering a pharmaceutical composition containing one or more Fel-d1-specific monoclonal antibodies or antigen-binding fragments of the issued claims to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein (see entire document, in particular, Abstract, Summary of the Invention, Claims, Para. 0120, Para. 0123, Para. 0126). The Fel-d1 antibodies can also prevent even more serious in vivo complications associated with exposure to Fel-d1 in a sensitized individual, such as asthmatic responses, anaphylaxis, or even death (Para. 0011). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The therapeutic compositions comprising the Fel-d1 antibodies or antigen-binding fragments can be administered at an initial dose of about 1 to about 600 mg (e.g. 300 mg each) and subsequent doses separated by at least 8 weeks, 10, weeks, 12 weeks or 14 weeks (Para. 0141-0144 and Para. 0280-0281). One or more Fel-d1 antibodies (antibody combination) can be administered sequentially in a single initial dose and then at one or more subsequent doses (Para. 0299). The additional Fel-d1 antibodies can be administered prior to, concurrent with, or after the administration of an anti-Fel dl antibody disclosed (Para. 0153-0154 and Para. 0297-0298). If the second Fel-d1 antibody is administered prior to or after the administration of the first Fel-d1 antibody, then the antibodies are necessarily formulated individually and administered sequentially. Specifically, it was shown that a single subcutaneous dose of REGN1908-1909 (a combination of Fel-d1 specific antibodies H4H1232N and H4H2636P presently recited in the instant and issued claims) (600 mg total, 1:1 antibody ratio) administered to human subjects having cat-induced allergic rhinitis and sensitization at screening but not currently living with a cat blocked the early allergic response to nasal challenge with cat hair extract and led to a clinically meaningful and sustained reduction in total nasal symptoms. Thus, the Fel-d1 specific antibodies can prevent allergen-induced allergic response (Example 11, Patient Population under Para. 0384, and Figure 8).
Agache further teaches that allergen challenge tests are established diagnostic tools for allergic disease, providing direct proof of the clinical relevance of a particular allergen (Abstract). In particular, Agache describes the bronchial allergen provocation test in which airway hyper-reactivity (AHR) is assessed by measuring decreases in FEV1 following allergen inhalation. A positive early airway response (EAR) is defined by a ≥ 20% fall in FEV1 from baseline, typically occurring within 30 minutes and resolving within 3 hours, with the EAR quantifiable as the area under the curve of percentage FEV1 decrease over the first 2 hours after challenge (“Bronchial allergen provocation test” section, in particular, “Rationale and Indications” as well as “Procedure” subsections). Thus, Agache teaches that a ≥ 20% fall in FEV1 within 2 hours of allergen challenge is a diagnostic indicator of allergy to that allergen.
Gherasim further teaches that in a house with a cat, it takes approximately 40 minutes for a cat-allergic person to develop asthma symptoms. In an environment exposure chamber (EEC), with a nebulized Fel d 1 concentration of 40 ng/m3 and with 10 L of ventilation per minute, the cumulative inhaled dose of Fel d 1 will be 16 ng in 40 minutes and can elicit an early asthmatic response (EAR) defined as a 20% drop in forced expiratory volume over 1 second (FEV1) during 2 hours of exposure . Thus, the exposure to cat allergen in the EEC corresponds to the natural exposure in terms of the cumulative Fel d 1 dose (Discussion, 2nd Paragraph and Section 2.1). Specifically, it is taught that cat-asthmatic patients with GINA 1 asthma (controlled intermittent asthma requiring step 1 treatment – short acting beta 2 agonists- as needed) are exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in the EEC and exited the EEC as soon as a 20% drop in FEV1 was observed (Abstract and Sections 2.1-2.4). As such, cat asthmatic patients with GINA 1 asthma represent a patient population that would receive therapeutic benefit from treatment with anti-allergy agents.
It would have been obvious to one of ordinary skill in the art to modify the method of the issued claims such that the Fel-d1 specific antibodies are administered to cat-allergic subjects – including those not living with a cat as taught by Orengo –who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 as taught by Agache and Gherasim. One of ordinary skill in the art would have been motivated to do so since Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR useful for diagnosing allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an EAR under exposure conditions modelling real-world patient environments. Orengo further teaches that Fel d 1 antibodies reduce allergic rhinitis or allergic asthma in cat-allergic subjects – including those not living with a cat – and provides suitable routes, dosages, and frequencies of administration for the Fel d 1 antibodies. Additionally, it would have been obvious to apply the method of issued claims to cat-allergic patients having GINA 1 asthma disclosed by Gherasim since they represent a patient population that would receive therapeutic benefit from anti-Fel d 1 treatment. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) to greater than 4 hours or decreases the incidence of EAR by about 20% relative to placebo when measured at day 8, 29, or 57 after administration. As such, the method taught by the combined teachings of the issued claims and prior art, having the same minimally required active steps and Fel-d1 specific antibodies of the instant claims, necessarily yield the same intended results. Therefore, one of ordinary skill in the art would expect that administration of the recited Fel-d1 antibodies can effectively treat cat-allergic subjects who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 – including those not living with a cat or having GINA 1 asthma.
Claims 1-3, 5, 7-9, 21-22, 25-27, 30-33, and 35-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 9079948B2 in view of Orengo et al, (WO2018118713A1, of record), hereinafter Orengo, and Agache et al (Agache, I et al. “In vivo diagnosis of allergic diseases--allergen provocation tests.” Allergy vol. 70,4 (2015): 355-65. doi:10.1111/all.12586, of record), hereinafter Agache, and Gherasim et al (Gherasim, Alina, et al. "Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC® environmental exposure chamber." Clinical & Experimental Allergy 50.2 (2020): 160-169, of record), hereinafter Gherasim.
The issued claims recite a pharmaceutical composition comprising a therapeutically effective amount of two Fel-d1 specific antibodies, wherein the first antibody has a VH/VL chain pair of SEQ ID NO: 18/26 and the second antibody has a VH/VL chain pair of SEQ ID NO: 306/314 (issued claims 1, 8, and 9). The VH/VL chain pair of SEQ ID NOs: 18/26 correspond to SEQ ID NOs: 18/26 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30 and 32. The VH/VL chain pair of SEQ ID NOs: 306/314 correspond to SEQ ID NOs: 306/314 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 308, 310, 312, 316, 318, and 320.
The issued claims do not recite a method of increasing tolerance to cat allergen (i.e. increasing the time to EAR or reducing incidence of EAR) in a subject having an allergy to the cat allergen Fel-d1, comprising administering one or more doses of the two Fel-d1 specific antibodies of the issued claims to the subject, wherein a) the subject has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3, b) the subject having a cat allergy has asthma or does not live with a cat, c) the subject has GINA stage 1 asthma, and d) the Fel d 1 antibodies are administered according to the routes of administration, frequency of administration, or dosage amounts recited in the instant clams.
However, Orengo discloses a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering a pharmaceutical composition containing one or more Fel-d1-specific monoclonal antibodies or antigen-binding fragments of the issued claims to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein (see entire document, in particular, Abstract, Summary of the Invention, Claims, Para. 0120, Para. 0123, Para. 0126). The Fel-d1 antibodies can also prevent even more serious in vivo complications associated with exposure to Fel-d1 in a sensitized individual, such as asthmatic responses, anaphylaxis, or even death (Para. 0011). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The therapeutic compositions comprising the Fel-d1 antibodies or antigen-binding fragments can be administered at an initial dose of about 1 to about 600 mg (e.g. 300 mg each) and subsequent doses separated by at least 8 weeks, 10, weeks, 12 weeks or 14 weeks (Para. 0141-0144 and Para. 0280-0281). One or more Fel-d1 antibodies (antibody combination) can be administered sequentially in a single initial dose and then at one or more subsequent doses (Para. 0299). The additional Fel-d1 antibodies can be administered prior to, concurrent with, or after the administration of an anti-Fel dl antibody disclosed (Para. 0153-0154 and Para. 0297-0298). If the second Fel-d1 antibody is administered prior to or after the administration of the first Fel-d1 antibody, then the antibodies are necessarily formulated individually and administered sequentially. Specifically, it was shown that a single subcutaneous dose of REGN1908-1909 (a combination of Fel-d1 specific antibodies H4H1232N and H4H2636P presently recited in the instant and issued claims) (600 mg total, 1:1 antibody ratio) administered to human subjects having cat-induced allergic rhinitis and sensitization at screening but not currently living with a cat blocked the early allergic response to nasal challenge with cat hair extract and led to a clinically meaningful and sustained reduction in total nasal symptoms. Thus, it was concluded that the Fel-d1 specific antibodies can prevent allergen-induced allergic response (Example 11, Patient Population under Para. 0384, and Figure 8).
Agache further teaches that allergen challenge tests are established diagnostic tools for allergic disease, providing direct proof of the clinical relevance of a particular allergen (Abstract). In particular, Agache describes the bronchial allergen provocation test in which airway hyper-reactivity (AHR) is assessed by measuring decreases in FEV1 following allergen inhalation. A positive early airway response (EAR) is defined by a ≥ 20% fall in FEV1 from baseline, typically occurring within 30 minutes and resolving within 3 hours, with the EAR quantifiable as the area under the curve of percentage FEV1 decrease over the first 2 hours after challenge (“Bronchial allergen provocation test” section, in particular, “Rationale and Indications” as well as “Procedure” subsections). Thus, Agache teaches that a ≥ 20% fall in FEV1 within 2 hours of allergen challenge is a diagnostic indicator of allergy to that allergen.
Gherasim further teaches that in a house with a cat, it takes approximately 40 minutes for a cat-allergic person to develop asthma symptoms. In an environment exposure chamber (EEC), with a nebulized Fel d 1 concentration of 40 ng/m3 and with 10 L of ventilation per minute, the cumulative inhaled dose of Fel d 1 will be 16 ng in 40 minutes and can elicit an early asthmatic response (EAR) defined as a 20% drop in forced expiratory volume over 1 second (FEV1) during 2 hours of exposure . Thus, the exposure to cat allergen in the EEC corresponds to the natural exposure in terms of the cumulative Fel d 1 dose (Discussion, 2nd Paragraph and Section 2.1). Specifically, it is taught that cat-asthmatic patients with GINA 1 asthma (controlled intermittent asthma requiring step 1 treatment – short acting beta 2 agonists- as needed) are exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in the EEC and exited the EEC as soon as a 20% drop in FEV1 was observed (Abstract and Sections 2.1-2.4). As such, cat asthmatic patients with GINA 1 asthma represent a patient population that would receive therapeutic benefit from treatment with anti-allergy agents.
It would have been obvious to one of ordinary skill in the art to administer the Fel-d1 specific antibodies of the issued claims to cat-allergic subjects – including those not living with a cat as taught by Orengo –who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 as taught by Agache and Gherasim. One of ordinary skill in the art would have been motivated to do so since Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR useful for diagnosing allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an EAR under exposure conditions modelling real-world patient environments. Orengo further teaches that the Fel d 1 antibodies of the issued claims can reduce allergic rhinitis or allergic asthma in cat-allergic subjects – including those not living with a cat – and also provides suitable routes, dosages, and frequencies of administration for the Fel d 1 antibodies. Additionally, it would have been obvious to apply the method of issued claims to cat-allergic patients having GINA 1 asthma disclosed by Gherasim since they represent a patient population that would receive therapeutic benefit from anti-Fel d 1 treatment. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) to greater than 4 hours or decreases the incidence of EAR by about 20% relative to placebo when measured at day 8, 29, or 57 after administration. As such, the method taught by the combined teachings of the issued claims and prior art, having the same minimally required active steps and Fel-d1 specific antibodies of the instant claims, necessarily yield the same intended results. Therefore, one of ordinary skill in the art would expect that administration of the recited Fel-d1 antibodies can effectively treat cat-allergic subjects who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 – including those not living with a cat or having GINA 1 asthma.
Claims 1-3, 5, 7-9, 21-22, 25-27, 30-33, and 35-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10047152B2 in view of Orengo et al, (WO2018118713A1, of record), hereinafter Orengo, and Agache et al (Agache, I et al. “In vivo diagnosis of allergic diseases--allergen provocation tests.” Allergy vol. 70,4 (2015): 355-65. doi:10.1111/all.12586, of record), hereinafter Agache, and Gherasim et al (Gherasim, Alina, et al. "Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC® environmental exposure chamber." Clinical & Experimental Allergy 50.2 (2020): 160-169, of record), hereinafter Gherasim.
The issued claims recite a nucleic acid encoding a Fel-d1 specific monoclonal antibody having a VH/VL chain pair of SEQ ID NO: 18/26 or 306/314; an expression vector comprising the nucleic acid; and a method of producing the Fel-d1 specific antibody comprising introducing the expression vector into isolated host cells, growing the cell under conditions permitting the production of the antibody, and recovering the antibody (issued claims 1, 4, 5, and 6). The VH/VL chain pair of SEQ ID NOs: 18/26 correspond to SEQ ID NOs: 18/26 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30 and 32. The VH/VL chain pair of SEQ ID NOs: 306/314 correspond to SEQ ID NOs: 306/314 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 308, 310, 312, 316, 318, and 320. The nucleic acids encoding the Fel-d1 antibodies render obvious the antibodies used in the claimed invention.
The issued claims do not recite a method of increasing tolerance to cat allergen (i.e. increasing the time to EAR or reducing incidence of EAR) in a subject having an allergy to the cat allergen Fel-d1, comprising administering one or more doses of the two Fel-d1 specific antibodies of the issued claims to the subject, wherein a) the subject has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3, b) the subject having a cat allergy has asthma or does not live with a cat, c) the subject has GINA stage 1 asthma, and d) the Fel d 1 antibodies are administered according to the routes of administration, frequency of administration, or dosage amounts recited in the instant clams.
However, Orengo discloses a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering a pharmaceutical composition containing one or more Fel-d1-specific monoclonal antibodies or antigen-binding fragments of the issued claims to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein (see entire document, in particular, Abstract, Summary of the Invention, Claims, Para. 0120, Para. 0123, Para. 0126). The Fel-d1 antibodies can also prevent even more serious in vivo complications associated with exposure to Fel-d1 in a sensitized individual, such as asthmatic responses, anaphylaxis, or even death (Para. 0011). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The therapeutic compositions comprising the Fel-d1 antibodies or antigen-binding fragments can be administered at an initial dose of about 1 to about 600 mg (e.g. 300 mg each) and subsequent doses separated by at least 8 weeks, 10, weeks, 12 weeks or 14 weeks (Para. 0141-0144 and Para. 0280-0281). One or more Fel-d1 antibodies (antibody combination) can be administered sequentially in a single initial dose and then at one or more subsequent doses (Para. 0299). The additional Fel-d1 antibodies can be administered prior to, concurrent with, or after the administration of an anti-Fel dl antibody disclosed (Para. 0153-0154 and Para. 0297-0298). If the second Fel-d1 antibody is administered prior to or after the administration of the first Fel-d1 antibody, then the antibodies are necessarily formulated individually and administered sequentially. Specifically, it was shown that a single subcutaneous dose of REGN1908-1909 (a combination of Fel-d1 specific antibodies H4H1232N and H4H2636P presently recited in the instant and issued claims) (600 mg total, 1:1 antibody ratio) administered to human subjects having cat-induced allergic rhinitis and sensitization at screening but not currently living with a cat blocked the early allergic response to nasal challenge with cat hair extract and led to a clinically meaningful and sustained reduction in total nasal symptoms. Thus, it was concluded that the Fel-d1 specific antibodies can prevent allergen-induced allergic response (Example 11, Patient Population under Para. 0384, and Figure 8).
Agache further teaches that allergen challenge tests are established diagnostic tools for allergic disease, providing direct proof of the clinical relevance of a particular allergen (Abstract). In particular, Agache describes the bronchial allergen provocation test in which airway hyper-reactivity (AHR) is assessed by measuring decreases in FEV1 following allergen inhalation. A positive early airway response (EAR) is defined by a ≥ 20% fall in FEV1 from baseline, typically occurring within 30 minutes and resolving within 3 hours, with the EAR quantifiable as the area under the curve of percentage FEV1 decrease over the first 2 hours after challenge (“Bronchial allergen provocation test” section, in particular, “Rationale and Indications” as well as “Procedure” subsections). Thus, Agache teaches that a ≥ 20% fall in FEV1 within 2 hours of allergen challenge is a diagnostic indicator of allergy to that allergen.
Gherasim further teaches that in a house with a cat, it takes approximately 40 minutes for a cat-allergic person to develop asthma symptoms. In an environment exposure chamber (EEC), with a nebulized Fel d 1 concentration of 40 ng/m3 and with 10 L of ventilation per minute, the cumulative inhaled dose of Fel d 1 will be 16 ng in 40 minutes and can elicit an early asthmatic response (EAR) defined as a 20% drop in forced expiratory volume over 1 second (FEV1) during 2 hours of exposure . Thus, the exposure to cat allergen in the EEC corresponds to the natural exposure in terms of the cumulative Fel d 1 dose (Discussion, 2nd Paragraph and Section 2.1). Specifically, it is taught that cat-asthmatic patients with GINA 1 asthma (controlled intermittent asthma requiring step 1 treatment – short acting beta 2 agonists- as needed) are exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in the EEC and exited the EEC as soon as a 20% drop in FEV1 was observed (Abstract and Sections 2.1-2.4). As such, cat asthmatic patients with GINA 1 asthma represent a patient population that would receive therapeutic benefit from treatment with anti-allergy agents.
It would have been obvious to one of ordinary skill in the art to administer the Fel-d1 specific antibodies of the issued claims to cat-allergic subjects – including those not living with a cat as taught by Orengo –who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 as taught by Agache and Gherasim. One of ordinary skill in the art would have been motivated to do so since Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR useful for diagnosing allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an EAR under exposure conditions modelling real-world patient environments. Orengo further teaches that the Fel d 1 antibodies of the issued claims can reduce allergic rhinitis or allergic asthma in cat-allergic subjects – including those not living with a cat – and also provides suitable routes, dosages, and frequencies of administration for the Fel d 1 antibodies. Additionally, it would have been obvious to apply the method of issued claims to cat-allergic patients having GINA 1 asthma disclosed by Gherasim since they represent a patient population that would receive therapeutic benefit from anti-Fel d 1 treatment. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) to greater than 4 hours or decreases the incidence of EAR by about 20% relative to placebo when measured at day 8, 29, or 57 after administration. As such, the method taught by the combined teachings of the issued claims and prior art, having the same minimally required active steps and Fel-d1 specific antibodies of the instant claims, necessarily yield the same intended results. Therefore, one of ordinary skill in the art would expect that administration of the recited Fel-d1 antibodies can effectively treat cat-allergic subjects who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 – including those not living with a cat or having GINA 1 asthma.
Claims 1-3, 5, 7-9, 21-22, 25-27, 30-33, and 35-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 12252530B2 in view of Orengo et al, (WO2018118713A1, of record), hereinafter Orengo, and Agache et al (Agache, I et al. “In vivo diagnosis of allergic diseases--allergen provocation tests.” Allergy vol. 70,4 (2015): 355-65. doi:10.1111/all.12586, of record), hereinafter Agache, and Gherasim et al (Gherasim, Alina, et al. "Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC® environmental exposure chamber." Clinical & Experimental Allergy 50.2 (2020): 160-169, of record), hereinafter Gherasim.
The issued claims recite a method of treating a patient who demonstrates a sensitivity to or an allergic reaction the cat allergen Fel d1 protein (or for treating at least one symptom or complication associated with a sensitivity to or allergic reaction against the cat allergen Fel-d1 protein) comprising administering to the patient a Fel-d1 specific monoclonal antibody having a VH/VL chain pair of SEQ ID NO: 306/314, wherein treatment results in a reduction in allergic rhinitis, allergic conjunctivitis, allergic asthma, or an anaphylactic response following exposure to cat allergen (issued claims 1, 4, 5, 8, 11, 13, 16, 17, and 18). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The method further comprises administering a second Fel-d1 specific antibody for example having the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30, and 32, corresponding to SEQ ID NOs: 20, 22, 24, 28, 30, and 32 of the instant claims (issued claims 9 and 10). Further recited is a pharmaceutical composition comprising one or more Fel-d1 specific antibodies having a VH/VL chain pair of SEQ ID NO: 18/26 and 306/314 (issued claims 24 and 30). The VH/VL chain pair of SEQ ID NOs: 18/26 correspond to SEQ ID NOs: 18/26 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30 and 32. The VH/VL chain pair of SEQ ID NOs: 306/314 correspond to SEQ ID NOs: 306/314 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 308, 310, 312, 316, 318, and 320.
The issued claims do not recite that 1) the subject has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3, 2) the subject having an allergy to a cat has asthma or does not live with a cat, 3) the subject has GINA stage 1 asthma, and 4) routes of administration, frequency of administration of more than one dosage, or dosage amounts.
However, Orengo discloses a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering a pharmaceutical composition containing one or more Fel-d1-specific monoclonal antibodies or antigen-binding fragments of the issued claims to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein (see entire document, in particular, Abstract, Summary of the Invention, Claims, Para. 0120, Para. 0123, Para. 0126). The Fel-d1 antibodies can also prevent even more serious in vivo complications associated with exposure to Fel-d1 in a sensitized individual, such as asthmatic responses, anaphylaxis, or even death (Para. 0011). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The therapeutic compositions comprising the Fel-d1 antibodies or antigen-binding fragments can be administered at an initial dose of about 1 to about 600 mg (e.g. 300 mg each) and subsequent doses separated by at least 8 weeks, 10, weeks, 12 weeks or 14 weeks (Para. 0141-0144 and Para. 0280-0281). One or more Fel-d1 antibodies (antibody combination) can be administered sequentially in a single initial dose and then at one or more subsequent doses (Para. 0299). The additional Fel-d1 antibodies can be administered prior to, concurrent with, or after the administration of an anti-Fel dl antibody disclosed (Para. 0153-0154 and Para. 0297-0298). If the second Fel-d1 antibody is administered prior to or after the administration of the first Fel-d1 antibody, then the antibodies are necessarily formulated individually and administered sequentially. Specifically, it was shown that a single subcutaneous dose of REGN1908-1909 (a combination of Fel-d1 specific antibodies H4H1232N and H4H2636P presently recited in the instant and issued claims) (600 mg total, 1:1 antibody ratio) administered to human subjects having cat-induced allergic rhinitis and sensitization at screening but not currently living with a cat blocked the early allergic response to nasal challenge with cat hair extract and led to a clinically meaningful and sustained reduction in total nasal symptoms. Thus, the Fel-d1 specific antibodies can prevent allergen-induced allergic response (Example 11, Patient Population under Para. 0384, and Figure 8).
Agache further teaches that allergen challenge tests are established diagnostic tools for allergic disease, providing direct proof of the clinical relevance of a particular allergen (Abstract). In particular, Agache describes the bronchial allergen provocation test in which airway hyper-reactivity (AHR) is assessed by measuring decreases in FEV1 following allergen inhalation. A positive early airway response (EAR) is defined by a ≥ 20% fall in FEV1 from baseline, typically occurring within 30 minutes and resolving within 3 hours, with the EAR quantifiable as the area under the curve of percentage FEV1 decrease over the first 2 hours after challenge (“Bronchial allergen provocation test” section, in particular, “Rationale and Indications” as well as “Procedure” subsections). Thus, Agache teaches that a ≥ 20% fall in FEV1 within 2 hours of allergen challenge is a diagnostic indicator of allergy to that allergen.
Gherasim further teaches that in a house with a cat, it takes approximately 40 minutes for a cat-allergic person to develop asthma symptoms. In an environment exposure chamber (EEC), with a nebulized Fel d 1 concentration of 40 ng/m3 and with 10 L of ventilation per minute, the cumulative inhaled dose of Fel d 1 will be 16 ng in 40 minutes and can elicit an early asthmatic response (EAR) defined as a 20% drop in forced expiratory volume over 1 second (FEV1) during 2 hours of exposure . Thus, the exposure to cat allergen in the EEC corresponds to the natural exposure in terms of the cumulative Fel d 1 dose (Discussion, 2nd Paragraph and Section 2.1). Specifically, it is taught that cat-asthmatic patients with GINA 1 asthma (controlled intermittent asthma requiring step 1 treatment – short acting beta 2 agonists- as needed) are exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in the EEC and exited the EEC as soon as a 20% drop in FEV1 was observed (Abstract and Sections 2.1-2.4). As such, cat asthmatic patients with GINA 1 asthma represent a patient population that would receive therapeutic benefit from treatment with anti-allergy agents.
It would have been obvious to one of ordinary skill in the art to modify the method of the issued claims such that the Fel-d1 specific antibodies are administered to cat-allergic subjects – including those not living with a cat as taught by Orengo –who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 as taught by Agache and Gherasim. One of ordinary skill in the art would have been motivated to do so since Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR useful for diagnosing allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an EAR under exposure conditions modelling real-world patient environments. Orengo further teaches that Fel d 1 antibodies reduce allergic rhinitis or allergic asthma in cat-allergic subjects – including those not living with a cat – and provides suitable routes, dosages, and frequencies of administration for the Fel d 1 antibodies. Additionally, it would have been obvious to apply the method of issued claims to cat-allergic patients having GINA 1 asthma disclosed by Gherasim since they represent a patient population that would receive therapeutic benefit from anti-Fel d 1 treatment. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) to greater than 4 hours or decreases the incidence of EAR by about 20% relative to placebo when measured at day 8, 29, or 57 after administration. As such, the method taught by the combined teachings of the issued claims and prior art, having the same minimally required active steps and Fel-d1 specific antibodies of the instant claims, necessarily yield the same intended results. Therefore, one of ordinary skill in the art would expect that administration of the recited Fel-d1 antibodies can effectively treat cat-allergic subjects who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 – including those not living with a cat or having GINA 1 asthma.
Claims 1-3, 5, 7-9, 21-22, 25-27, 30-33, and 35-46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of co-pending Application No. 19053152 in view of Orengo et al, (WO2018118713A1, of record), hereinafter Orengo, and Agache et al (Agache, I et al. “In vivo diagnosis of allergic diseases--allergen provocation tests.” Allergy vol. 70,4 (2015): 355-65. doi:10.1111/all.12586), hereinafter Agache, and Gherasim et al (Gherasim, Alina, et al. "Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC® environmental exposure chamber." Clinical & Experimental Allergy 50.2 (2020): 160-169), hereinafter Gherasim.
The co-pending claims recite a method of treating a patient who demonstrates a sensitivity to or an allergic reaction the cat allergen Fel d1 protein (or for treating at least one symptom or complication associated with a sensitivity to or allergic reaction against the cat allergen Fel-d1 protein) comprising administering to the patient one or more Fel-d1 specific monoclonal antibodies having a VH/VL chain pair of SEQ ID NO: 18/26 or 306/314, wherein treatment results in a reduction in allergic rhinitis, allergic conjunctivitis, allergic asthma, or an anaphylactic response following exposure to cat allergen (co-pending claims 22-24 and 31-36). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The VH/VL chain pair of SEQ ID NOs: 18/26 correspond to SEQ ID NOs: 18/26 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 20, 22, 24, 28, 30 and 32. The VH/VL chain pair of SEQ ID NOs: 306/314 correspond to SEQ ID NOs: 306/314 of the instant claims and fully comprise the CDRs of SEQ ID NOs: 308, 310, 312, 316, 318, and 320.
The co-pending claims do not recite that 1) the subject has a ≥ 20% fall in forced expiratory volume over one second (FEV1) within 2 hours during a cat allergen challenge in an environment exposure unit (EEU), wherein the cat allergen challenge comprises exposure to Feld1 allergen aerosolized into the EEU at 40 ng/m3, 2) the subject having an allergy to a cat has asthma or does not live with a cat, 3) the subject has GINA stage 1 asthma, and 4) routes of administration, frequency of administration of more than one dosage, or dosage amounts.
However, Orengo discloses a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering a pharmaceutical composition containing one or more Fel-d1-specific monoclonal antibodies or antigen-binding fragments of the issued claims to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein (see entire document, in particular, Abstract, Summary of the Invention, Claims, Para. 0120, Para. 0123, Para. 0126). The Fel-d1 antibodies can also prevent even more serious in vivo complications associated with exposure to Fel-d1 in a sensitized individual, such as asthmatic responses, anaphylaxis, or even death (Para. 0011). Since the Fel-d1 specific antibodies can reduce allergic rhinitis or allergic asthma in a subject, the subject necessarily has either allergic rhinitis or asthma. The therapeutic compositions comprising the Fel-d1 antibodies or antigen-binding fragments can be administered at an initial dose of about 1 to about 600 mg (e.g. 300 mg each) and subsequent doses separated by at least 8 weeks, 10, weeks, 12 weeks or 14 weeks (Para. 0141-0144 and Para. 0280-0281). One or more Fel-d1 antibodies (antibody combination) can be administered sequentially in a single initial dose and then at one or more subsequent doses (Para. 0299). The additional Fel-d1 antibodies can be administered prior to, concurrent with, or after the administration of an anti-Fel dl antibody disclosed (Para. 0153-0154 and Para. 0297-0298). If the second Fel-d1 antibody is administered prior to or after the administration of the first Fel-d1 antibody, then the antibodies are necessarily formulated individually and administered sequentially. Specifically, it was shown that a single subcutaneous dose of REGN1908-1909 (a combination of Fel-d1 specific antibodies H4H1232N and H4H2636P presently recited in the instant and issued claims) (600 mg total, 1:1 antibody ratio) administered to human subjects having cat-induced allergic rhinitis and sensitization at screening but not currently living with a cat blocked the early allergic response to nasal challenge with cat hair extract and led to a clinically meaningful and sustained reduction in total nasal symptoms. Thus, the Fel-d1 specific antibodies can prevent allergen-induced allergic response (Example 11, Patient Population under Para. 0384, and Figure 8).
Agache further teaches that allergen challenge tests are established diagnostic tools for allergic disease, providing direct proof of the clinical relevance of a particular allergen (Abstract). In particular, Agache describes the bronchial allergen provocation test in which airway hyper-reactivity (AHR) is assessed by measuring decreases in FEV1 following allergen inhalation. A positive early airway response (EAR) is defined by a ≥ 20% fall in FEV1 from baseline, typically occurring within 30 minutes and resolving within 3 hours, with the EAR quantifiable as the area under the curve of percentage FEV1 decrease over the first 2 hours after challenge (“Bronchial allergen provocation test” section, in particular, “Rationale and Indications” as well as “Procedure” subsections). Thus, Agache teaches that a ≥ 20% fall in FEV1 within 2 hours of allergen challenge is a diagnostic indicator of allergy to that allergen.
Gherasim further teaches that in a house with a cat, it takes approximately 40 minutes for a cat-allergic person to develop asthma symptoms. In an environment exposure chamber (EEC), with a nebulized Fel d 1 concentration of 40 ng/m3 and with 10 L of ventilation per minute, the cumulative inhaled dose of Fel d 1 will be 16 ng in 40 minutes and can elicit an early asthmatic response (EAR) defined as a 20% drop in forced expiratory volume over 1 second (FEV1) during 2 hours of exposure . Thus, the exposure to cat allergen in the EEC corresponds to the natural exposure in terms of the cumulative Fel d 1 dose (Discussion, 2nd Paragraph and Section 2.1). Specifically, it is taught that cat-asthmatic patients with GINA 1 asthma (controlled intermittent asthma requiring step 1 treatment – short acting beta 2 agonists- as needed) are exposed to 40 ng/m3 of airborne cat allergen for a maximum of 2 hours in the EEC and exited the EEC as soon as a 20% drop in FEV1 was observed (Abstract and Sections 2.1-2.4). As such, cat asthmatic patients with GINA 1 asthma represent a patient population that would receive therapeutic benefit from treatment with anti-allergy agents.
It would have been obvious to one of ordinary skill in the art to modify the method of the co-pending claims such that the Fel-d1 specific antibodies are administered to cat-allergic subjects – including those not living with a cat as taught by Orengo –who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 as taught by Agache and Gherasim. One of ordinary skill in the art would have been motivated to do so since Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR useful for diagnosing allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an EAR under exposure conditions modelling real-world patient environments. Orengo further teaches that Fel d 1 antibodies reduce allergic rhinitis or allergic asthma in cat-allergic subjects – including those not living with a cat – and provides suitable routes, dosages, and frequencies of administration for the Fel d 1 antibodies. Additionally, it would have been obvious to apply the method of issued claims to cat-allergic patients having GINA 1 asthma disclosed by Gherasim since they represent a patient population that would receive therapeutic benefit from anti-Fel d 1 treatment. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) to greater than 4 hours or decreases the incidence of EAR by about 20% relative to placebo when measured at day 8, 29, or 57 after administration. As such, the method taught by the combined teachings of the co-pending claims and prior art, having the same minimally required active steps and Fel-d1 specific antibodies of the instant claims, necessarily yield the same intended results. Therefore, one of ordinary skill in the art would expect that administration of the recited Fel-d1 antibodies can effectively treat cat-allergic subjects who demonstrate a ≥ 20% fall in FEV1 within 2 hrs of exposure to Feld1 aerosolized into an EEU at 40 ng/m3 – including those not living with a cat or having GINA 1 asthma.
Response to Arguments
Applicant's arguments filed 02/13/2026 have been fully considered but they are not persuasive.
With respect to rejections made under 35 USC 103, Applicant argues the following points:
Orengo contains no clinical trial data in asthma patients and does not assess asthma-specific endpoints such as early asthmatic response (EAR). Instead, Orengo focuses on a nasal allergen challenge (NAC) in allergic rhinitis patients and measures nasal endpoints such as total nasal symptom score (TNSS), visual analog scale (VAS), and peak nasal inspiratory flow (PNIF). Dose adjustments are based on changes in area under the curve (AUC) for TNSS. Thus, Orengo does not teach or suggest treating asthmatic-specific responses.
Therapeutic efficacy in allergic rhinitis does not provide a reasonable expectation of success in allergic asthma. In particular, the applicant cites Siddal which demonstrated that intranasal GSK2245035 (a TLR7 agonist) reduced nasal symptoms in allergic rhinitis but did not attenuate early or late asthmatic responses in patients with mild asthma. Thus, Applicant contends that an agent’s disease-modifying activity and subsequent potential clinical utility in treating allergic rhinitis do not translate to equivalent therapeutic efficacy for treating allergic asthma.
Neither Agache nor Gherasim address or suggest a method for treating EAR specifically in cat-allergic patients with asthma. While Agache teaches that undergoing BAPT elicits EAR in patients, it does not disclose specific therapeutic strategies to resolve EAR. Similarly, Gherasim observed that air cleaners prevented early and late asthmatic responses in asthmatic patients during cat allergen exposure, but did not teach a method to specifically treat EAR. Further, patient variability suggests that not all GINA 1 asthma patients exhibit EAR, in this case 7 out of 31 patients. Thus, Applicant asserts that, like Orengo, Agache and Gherasm target a different patient population and therapeutic outcome than what is presently claimed.
In response to Applicant’s first argument, the Examiner notes that disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989) (MPEP 2123). In this case, Orengo generally teaches a method for treating a patient having an allergy to the cat allergen Fel d1 comprising administering the Fel-d1-specific monoclonal antibodies of the instant claims to the patient in order to reduce sensitivity to or duration of an allergic reaction (or reduce allergic rhinitis or allergic asthma) to a cat, cat dander, cat hair or an extract thereof, or to Fel d1 protein. Per the instant claims, administration of one or more doses of the two Fel-d1 specific antibodies to a patient having an allergy to Fel d1 allergen increases the time to early asthmatic response (EAR) or prevents cat-allergen induced EAR. As such, the method of the Orengo having the same minimally required active steps and Fel-d1 specific antibodies, encompass treating asthmatic-specific responses contrary to Applicant’s assertions.
Further, allergic rhinitis and asthma are often considered clinical manifestations of the same condition, the chronic allergic respiratory syndrome. Both are characterized by chronic inflammation triggered by allergens that stimulate IgE production and release mediators like histamine and leukotrienes. The difference between rhinitis and asthma is primarily the anatomical location—upper vs lower airway—and clinical symptoms (sneezing vs. wheezing) not the initiating molecular mechanism (Jeffrey et al, see Abstract, Introduction, and “Interactions between asthma and allergic rhinitis” section; Owen, see Abstract and Introduction).
In response to Applicant’s second argument, the Examiner notes that obviousness does not require absolute predictability. 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”)) (emphasis added) (MPEP 2143.02). As stated earlier, artisans would have reasonably expected that Fel d1-neutralizing antibodies would reduce allergen-induced early asthmatic response given the shared IgE-mediated pathway between allergic rhinitis and allergic asthma. Further, because the mechanisms of action are distinct, failure of a TLR7 agonist – GSK2245035—to reduce early and late asthmatic responses does not meaningfully inform whether allergen-neutralizing monoclonal antibodies that prevent IgE crosslinking on effector cells would attenuate allergen-induced EAR. As such, a useful comparison cannot be made between mechanistically unrelated agents. Notably, omalizumab is known to attenuate the early asthmatic response as evidenced by a significantly smaller reduction in FEV1 after allergen challenge and significant increases in PC15 and PC20 (the concentration of allergen needed to cause a 15% and 20% drop, respectively, in FEV1 (Busse, see Introduction on Page S12). Omalizumab and the REGN1908/1909 antibody cocktail (presently claimed) have a similar mechanism of action in reducing the early asthmatic response by interrupting the IgE-mediated allergic cascade: both therapies prevent the cross-linking of IgE receptors on mast cells and other effector cells, which is the key trigger for the release of inflammatory mediators and subsequent allergic response (Instant Specification: Para. 0008 and 0158; de Blay et al, third paragraph under Introduction on Pages 1437-1438 and first paragraph on Page 1445; Konstantinou et al, third paragraph under Discussion on Page 4; Galli et al, see entire document, in particular Box 1: The basics of IgE antibodies and mast cells in allergy). As such, previous studies on the therapeutic efficacy of omalizumab in asthma established a reasonable expectation of success that other monoclonal antibodies that prevent the cross-linking of IgE receptors on effector cells (including the claimed Fel-d1 antibodies) can attenuate the early asthmatic response to allergen. Therefore, the findings of Siddall do not undermine the reasonable expectation that Fel d1-specific monoclonal antibodies, which directly neutralize the allergen and prevent IgE-crosslinking, would attenuate allergen-induced early asthmatic response discussed above.
In response to Applicant’s third argument, 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). Obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Agache establishes that a ≥ 20% fall in FEV1 within 2 hours defines an EAR indicates having an allergy to a specific allergen; and Gherasim demonstrates that Fel d1 allergen aerosolized at 40 ng/m3 into an EEU induces an EAR under exposure conditions modelling real-world patient environments. Further, Gherasim identifies cat-allergic patients having GINA 1 asthma, which are a patient population that could receive therapeutic benefit from anti-allergy treatment such as the recited Fel-d1 antibodies. Thus, the combined teachings of the prior art render obvious the instantly claimed invention. Therefore, the rejection under 35 USC 103 is maintained.
Conclusion
No claims are allowable.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641