DETAILED ACTION
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 preliminary amendments received October 14, 2024 are acknowledged.
Claims 30-32 have been canceled.
Claims 5-14 and 16-29 have been amended.
Claims 1-29 are pending in the instant application.
Information Disclosure Statement
The IDs forms received 2/7/2024 and 7/9/2025 are acknowledged and the references cited therein have been considered.
Specification
The substitute specification received 10/14/2024 is acknowledged.
The instant application discloses methods of administering the anti-IgE antibody named ligelizumab for treating urticaria. The specification discloses that this antibody was first disclosed in US patent 7,531,169, and in some places indicates that the VH and VL for this antibody are SEQ ID numbers 61 and 62, while other places indicate that they are SEQ ID NOs:1 and 2 (compare the middle of page 7, the paragraph spanning pages 8 and 9, the bottom of page 16, the middle of page 17, instant claim 2, and the sequence listing itself). It should be noted that the sequence listing only has 8 sequences total. Appropriate correction to the specification to correctly identify the relevant biological sequences to which applicant is referring is required.
Claim Rejections - 35 USC § 102
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 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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 8-10, 12-14, and 16-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NCT02477332 (NPL reference 2 on the 2/7/2024 IDS dated 22 June 2015; it should be noted that applicant has not provided a copy of this document as part of the IDS submission and as such the copy made of record by applicant in parent application 17/041,291 has been enclosed with this office action for completeness of the record).
The ‘332 clinical trial indicates that human chronic spontaneous urticaria patients were administered QGE031 subcutaneously every four weeks, with dosages of 24 mg, 72 mg, and 240 mg being administered as part of differing experimental arms (see particularly the Arms and Interventions section beginning on page 2 of the printout as originally provided by applicant). Notably, it is disclosed that patients had a diagnosis of chronic spontaneous urticaria refractory to standard care and were aged 18-75 years old (see particularly the Eligibility Criteria section beginning on page 7). As per pages 8, 16, and 17 of the instant specification as well as the enclosed sequence alignments, QGE031 is the same antibody as ligelizumab which is the antibody named CL-2C in US 7,531,169, and this antibody has the variable domain sequences of SEQ ID numbers 1-2 and the CDR sequences of SEQ ID NOs:3-8. Measured primary outcomes are disclosed as including the percentage of patients with a hives severity score (HSS) of zero at week 12. Additionally, given the at the antibody is disclosed as being administered subcutaneously, the antibody must be in liquid form at the time of injection. It should be noted that instant claim 13 simply recites the intended results of the claimed administration protocol. Claim 13 as presently recited does not recite an active process step requiring collection of data, it simply indicates what applicant hopes to achieve by administering ligelizumab subcutaneously to the indicated patient population at the recited time intervals and doses. Given that the clinical trial teaches administering the same drug to the same patient population at the same route, dose and time interval as that which is presently claimed, any and all outcomes of such an administration, whether measured or not, are inherent outcomes of the therapeutic administration. See MPEP 2112. Therefore, the prior art anticipates the instant claimed invention.
Claims 1-5, 7, 9, 11, 13-21, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clinical Trial Protocol_NCT03437278 (NPL reference 5 on the 2/7/2024 IDS, and note the document indicates its release date was January 18, 2018 as is also indicated on the IDS listing).
The clinical trial protocol discloses that subjects aged 12-18 with chronic spontaneous urticaria which is clinically unresponsive to H1-antihistamie therapy are to be subcutaneously administered either 24 mg or 120 mg ligelizumab every 4 weeks (see entire document, particularly the protocol summary beginning on page 11 and section 3.1, Study Design, on page 19). Notably such patients are to have their symptoms evaluated via the HSS7 and UAS7 criteria (see particularly Study Objectives and Endpoints beginning on page 17). Such patients also are to have ligelizumab injected at 120 mg in a volume of 1 mL (see particularly Table 3-1 on page 23). It should be noted that as per pages 8, 16, and 17 of the instant specification as well as the enclosed sequence alignments, QGE031 is the same antibody as ligelizumab which is the antibody named CL-2C in US 7,531,169, and this antibody has the variable domain sequences of SEQ ID numbers 1-2 and the CDR sequences of SEQ ID NOs:3-8. Therefore, the prior art anticipates the instant claimed invention.
Claim Rejections - 35 USC § 103
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 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.
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 1-4, 7, 8, 11-21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03437278 (NPL reference 3 on the 2/7/2024 IDS) in view of Ertas (NPL reference 7 on the 2/7/2024 IDS). It should be noted that copies of the aforementioned documents were not provided as part of the IDS submission and as such the copies made of record by applicant in parent application 17/041,291 have been enclosed with this office action for completeness of the record.
The ‘278 clinical trial indicates that human chronic spontaneous urticaria patients were administered either high or low doses of ligelizumab every four weeks, that ligelizumab comes in 120 mg per 1mL liquid in a vial (see entire document, particularly the Arms and Interventions section). It further discloses that the patients were aged 12-18 years and had a diagnosis of CSU refractory to H1 antihistamines. These teachings differ from the instant claimed invention in that the dose of ligelizumab is not disclosed nor is subcutaneous injection. Note that as per the instant specification, ligelizumab is an anti-IgE antibody that comprises the biological sequences of SEQ ID numbers 1-8.
Ertas discloses subcutaneous administration of the anti-IgE antibody omalizumab at a dose of 150 mg every four weeks and 300 mg every four weeks is effective for the treatment of CSU (see entire document, particularly section 3.3 Dose regimens and assessment of patients beginning on page 109).
Therefore, it would have been obvious to a person of ordinary skill in the art to use the route and dosing information of Ertas when practicing the methods disclosed in the ‘278 clinical trial. Artisans would have been motived to use the subcutaneous route and doses disclosed in Ertas as such a route and dosing are known to be effective in treating human CSU, and note that Ertas even supplies a “high” and “low” dose (i.e. 300 mg and 150 mg respectively) for the administered anti-IgE antibodies. It should be noted that the instant claims recite “about” which broadens the claimed invention beyond the exact numbers presently recited in the instant claims. While the paragraph spanning pages 8 and 9 of the instant specification exemplifies what is meant by “about” such guidance is not a definition and is not therefore limited to only + or - 10% of any particular number. As such, 150 is reasonably about 120, while 300 is reasonably about 240. It should be noted that even if the instant claims did not recite the term “about”, skilled artisans, which in the instant case reasonably are physicians and other highly skilled medical professionals, routinely adjust dosing to best meet the needs of their patients. Given that the clinical trial explicitly indicates that ligelizumab is to be administered every four weeks to treat CSU, determining the appropriate dose is a results effective variable, wherein the dose (i.e. the variable) controls the outcome, i.e. effective treatment of CSU. Also, as is discussed in MPEP 2144.05, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). It should be noted that the instant claims themselves, such as independent claim 1, explicitly recite a log range of doses, all of which when administered every four weeks subcutaneously are effective in treating CSU and thus there does not appear to be any criticality with regard to the drug masses recited as part of the instant claims.
Claims 1-13, and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over US 7,531,169 in view of Ertas (NPL reference 7 on the 2/7/2024 IDS).
The ‘169 patent discloses high affinity humanized antibodies that bind human IgE and their administration to treat disease including urticaria (see entire document, particularly the abstract and claims, most notably claim 11). As evidenced by the enclosed sequence alignments, the antibody of the issued product and method claims of the ‘169 patent has the same biological sequence as those of ligelizumab as recited in the instant claims. The ‘169 patent discloses subcutaneous administration of antibodies, as well as the routine nature of adjusting dosing to best meet the needs of the patient, with subcutaneous injection preferred for chronic administration (see particularly columns 24 and 25). It is disclosed that the anti-IgE antibodies are to be in therapeutic formulations comprising buffers which can be liquid or lyophilized (see particularly columns 20-22). These teachings differ from the present claimed invention in that neither the numerical mass values of the instant claims nor the four week interval between administrations is explicitly disclosed by the ‘169 patent.
Ertas discloses subcutaneous administration of the anti-IgE antibody omalizumab at a dose of 150 mg every four weeks and 300 mg every four weeks is effective in the treatment of CSU (see entire document, particularly section 3.3 Dose regimens and assessment of patients beginning on page 109).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the methods of the ‘169 patent to include subcutaneous administration every four weeks at a dose of about 150 or 300 mg for the treatment of chronic spontaneous urticaria. This is because the ‘169 patent teaches the administration of ligelizumab subcutaneously to treat urticaria and given that both omalizumab and ligelizumab are anti-IgE antibodies that bind to the CH3 domain of human IgE thereby disrupting the ability of IgE to be bound by FcRI (see for example columns 2-3 of the ‘169 patent as well as page 108 of Ertas) and thus have comparable mechanisms of action as they bind a similar/overlapping epitope in the Fc domain of human IgE, it is reasonable that the two antibodies can be substituted for each other while enjoying a reasonable expectation of success. As taught by Ertas, it was known that CSU could be successfully treated by subcutaneous administration of anti-IgE antibodies every four weeks, and given the similar epitope in IgE bound by omalizumab and ligelizumab using dosing information for omalizumab is a logical starting point that could be further modified to best meet the needs of the patient, especially as doing so is routine in the art as taught by the ‘169 patent. It should be noted that the instant claims recite “about” which broadens the claimed invention beyond the exact numbers presently recited in the instant claims. While the paragraph spanning pages 8 and 9 of the instant specification exemplifies what is meant by “about” such guidance is not a definition and is not therefore limited to only + or - 10% of any particular number. As such, 150 is reasonably about 120, while 300 is reasonably about 240. Even if the instant claims did not recite the term “about”, skilled artisans, which in the instant case reasonably are physicians and other highly skilled medical professionals, routinely adjust dosing to best meet the needs of their patients as has already been discussed above. Further, determining the appropriate dose is a results effective variable, wherein the dose (i.e. the variable) controls the outcome, i.e. effective treatment of CSU. Indeed, as is discussed in MPEP 2144.05, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). It should be noted that the instant claims themselves, such as independent claim 1, explicitly recite a log range of doses, all of which when administered every four weeks subcutaneously are effective in treating CSU and thus there does not appear to be any criticality with regard to any of the drug masses recited as part of the instant claimed inventions.
Additionally, claim 13 recites outcomes in the patient that the practitioner of the claimed method hopes to achieve via the claimed administration. Note that the practitioner does nothing other than administer the drug, and thus how the patient does or does not respond clinically is not under the control of the method’s practitioner and cannot reasonably be said to be limiting as it is impossible to know with certainty at the time of administration how a patient will respond to said administration. See particularly MPEP 2111.02.
Claims 23-25, 27 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over NCT02477332 (NPL reference 2 on the 2/7/2024 IDS dated 22 June 2015) as applied to claims 1-6, 8-10, 12-14, and 16-21 above, and further in view of Michael et al. (US 2015/0150982).
The teachings of the ‘332 clinical trial document have been discussed above and differ from that which is presently claimed in that said document does not discuss administration via pre-filled syringes or autoinjectors.
Michael et al. disclose various formulations for antibody drugs that are to be administered subcutaneously, with the use of preconditioned injection devices including pre-filled syringes and autoinjectors offering the advantages of easier administration by non-professionals, such as by the patient in the patient’s home (see entire document, particularly pages 8 and 9, most particularly paragraphs [0088] and [0096-0098]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time of the invention that the methods pf the ‘332 clinical trial document could be practiced using an autoinjector or similar prefilled device. Artisans would be motivated to do so as such devices are easier for patients to administer to themselves in a home setting.
Claims 22, 24, and 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial Protocol_NCT03437278 (NPL reference 5 on the 2/7/2024 IDS) as applied to claims 1-5, 7, 9, 11, 13-21, and 23 above, and further in view of Michael et al. (US 2015/0150982).
The teachings of the ‘278 clinical trial protocol document have been discussed above and differ from that which is presently claimed in that said document does not discuss administration via pre-filled syringes or autoinjectors.
Michael et al. disclose various formulations for antibody drugs that are to be administered subcutaneously, with the use of preconditioned injection devices including pre-filled syringes and autoinjectors offering the advantages of easier administration by non-professionals, such as by the patient in the patient’s home (see entire document, particularly pages 8 and 9, most particularly paragraphs [0088] and [0096-0098]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time of the invention that the methods of the ‘278 protocol could be practiced using an autoinjector or similar prefilled device. Artisans would be motivated to do so as such devices are easier for patients to administer to themselves in a home setting.
Claims 22 and 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03437278 (NPL reference 3 on the 2/7/2024 IDS) in view of Ertas (NPL reference 7 on the 2/7/2024 IDS) as applied to claims 1-4, 7, 8, 11-21, and 23 above, and further in view of Michael et al. (US 2015/0150982).
The combined teachings of references 3 and 7 of the 2/2/2024 IDS have been discussed above and differ from that which is presently claimed in that said documents does not disclose administration via pre-filled syringes or autoinjectors.
Michael et al. disclose various formulations for antibody drugs that are to be administered subcutaneously, with the use of preconditioned injection devices including pre-filled syringes and autoinjectors offering the advantages of easier administration by non-professionals, such as by the patient in the patient’s home (see entire document, particularly pages 8 and 9, most particularly paragraphs [0088] and [0096-0098]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time of the invention that the ligelizumab administration methods rendered obvious by the teachings of the prior art could be practiced using an autoinjector or similar prefilled device. Artisans would be motivated to do so as such devices are easier for patients to administer to themselves in a home setting.
Claims 24-29 are rejected under 35 U.S.C. 103 as being unpatentable over US 7,531,169 in view of Ertas (NPL reference 7 on the 2/7/2024 IDS) as applied to claims 1-13, and 20-23 above, and further in view of Michael et al. (US 2015/0150982).
The combined teachings of references 3 and 7 of the 2/2/2024 IDS have been discussed above and differ from that which is presently claimed in that said documents does not disclose administration via pre-filled syringes or autoinjectors.
Michael et al. disclose various formulations for antibody drugs that are to be administered subcutaneously, with the use of preconditioned injection devices including pre-filled syringes and autoinjectors offering the advantages of easier administration by non-professionals, such as by the patient in the patient’s home (see entire document, particularly pages 8 and 9, most particularly paragraphs [0088] and [0096-0098]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time of the invention that the ligelizumab administration methods rendered obvious by the teachings of the prior art could be practiced using an autoinjector or similar prefilled device. Artisans would be motivated to do so as such devices are easier for patients to administer to themselves in a home setting.
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1644
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