DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 8, 2026 has been entered.
Priority
The instant application claims priority to the U.S. Provisional Application 62/746,174, filed October 16, 2018; however, 62/746,174 does not provide basis for the fixed doses nor fixed doses tiered by weight found in claims 29, 30, 31, and 32. Thus, claims 29, 30, 31, 32, and 33, which depend from claim 30, are given priority to October 16, 2019 – the actual filing date.
Should Applicant disagree with the above assessment, he/she may point to the specific paragraphs within 62/746,174 which provide basis for the fixed doses and fixed doses tiered by weight.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 5-8, 10-16, 27, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Finney et al. (WO 2014/019727 A1; Published: Feb 6, 2014) in view of the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) and as evidenced by International Nonproprietary Names for Pharmaceutical Substances (WHO Drug Information. 30(2): 241-357; Published: 2016).
Regarding claim 1, Finney et al. teaches a method of treating a patient having myasthenia gravis with an anti-FcRn antibody comprising CDRs having the sequences given in SEQ ID NOs 1-6, which are 100% identical to instant SEQ ID NOs: 1-6; see claims 1-8, 41, and 42. Regarding claims 6-8, the anti-FcRn antibody taught by Finney et al. comprises heavy and light variable chains comprising SEQ ID NOs: 29 and 15, respectively, which are 100% identical to instant SEQ ID NOs: 29 and 15; see claim 10. Additionally, regarding claim 11, the anti-FcRn antibody taught by Finney et al. comprises heavy and light chains comprising SEQ ID NOs: 72, 87, or 43, and 22, respectively, which are 100% identical to instant SEQ ID NOs: 72, 87, or 43, and 22; see claim 18. Regarding claim 12, the identifiers UCB7665 or rozanolixizumab, which are understood to be alternative identifiers for the same anti-FcRn antibody, are evidenced by the WHO Drug Information to refer to the anti-FcRn antibody comprising the heavy and light variable regions of SEQ ID NOs: 29 and 15 and the heavy and light chains having 100% identity through their length to SEQ ID NO: 43 and 22; see pages 309-310.
Further, regarding claims 5 and 10, the anti-FcRn antibody taught by Finney et al. is a humanized, full-length antibody selected from the group consisting of IgG1, IgG4, and IgG4P; see claims 9, 16, and 17. Regarding claims 13 and 14, the anti-FcRn antibody taught by Finney et al. has a binding affinity for human FcRn of 100pM or less when measures at pH6 - pH7.4; see claims 20 and 21. Further, regarding claims 15 and 16, the anti-FcRn antibody can be provided as a pharmaceutical composition and which further comprises one or more additional active ingredients; see claims 37 and 38.
Regarding the doses in claim 1, Finney et al. teaches that a therapeutically effective amount will be from 0.01 mg/kg to 500 mg/kg; see page 29 lines 20-21. Finney et al. Figures 9 and 12-16 teaches administering multiple, up to 10, doses of 20mg/kg to non-human primates. Additionally, Finney et al. Figures 20, 21, and 23 teach administering 10mg/kg to transgenic mice. Further, Figures 13 and 16 teach administering 4 or 10 repeat doses. Regarding claim 1, Finney et al. teaches that the anti-FcRn antibody can be administered subcutaneously or intravenously; see page 31 lines 23-25.
Regarding weekly dosing in claims 19-21 and 23, Examples 7 and 8 demonstrate that IgG levels reach the lowest point at day 7 following administration and begin to rise thereafter. Further, Finney et al. teaches possible repeat dosing to achieve long-term maintenance of low plasma IgG concentration; see page 25 line 19-20.
While Finney et al. teaches that the antibody is specific to human FcRn, the reference does not explicitly teach treating human subjects with myasthenia gravis. Additionally, Finney et al. does not teach the use of the anti-FcRn for the treatment of generalized myasthenia gravis classified as moderate to severe or in patients with anti-AChR or anti-MuSK antibody-positive disease, nor that additional doses following doses 4, 5, or 6 at weekly intervals are administered at lower and/or less frequent doses.
Regarding claims 1, 27, and 28, the Clinical Trial Listing for NCT03052751 teaches treating human patients with generalized myasthenia gravis who are classified as moderate to severe with the anti-FcRn antibody, UCB7665; see Study Description: Brief Summary. Further, the clinical trial listing teaches treating humans with anti-AChR and/or anti-MuSK antibody-positive disease; see Inclusion Criteria.
It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat human patients with moderate to severe, generalized myasthenia gravis with the anti-FcRn antibody taught by Finney et al. because Finney et al. teaches that the anti-FcRn antibody can be used to treat myasthenia gravis and the Clinical Trial Listing for NCT03052751 teaches using the same antibody to treat moderate to severe, generalized myasthenia gravis.
Regarding doses and frequency, it would have been obvious to one of ordinary skill in the art that patients having myasthenia gravis, a chronic disease, would benefit from weekly and long-term maintenance doses. One would be motivated to treat weekly because Finney et al. exemplifies weekly dosing and plasma IgG levels were demonstrated to reached the lowest point at day 7 following administration. The teaching that plasma IgG levels reach the lowest concentration at day 7, would have given one of ordinary skill in the art a reasonable expectation of success at maintaining low plasma IgG levels when administered on a weekly schedule.
It would have been obvious to one of ordinary skill in the art to use the dosing and frequency schedules and routes of administration taught by Finney et al. as starting points for optimization by routine experimentation. Indeed, Finney et al. teaches that dosing and frequency schedules demonstrated in animal models may be useful for determining the dosing and routes of administration in humans and that the therapeutically effective amount may be determined by routine experimentation; see page 29 lines 11-15 and 19-20. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Finney et al. (WO 2014/019727 A1; Published: Feb 6, 2014) in view of the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) and as evidenced by International Nonproprietary Names for Pharmaceutical Substances (WHO Drug Information. 30(2): 241-357; Published: 2016) as applied to claim(s) 1, 5-16, 18-23, 27, and 28 above, and further in view of the Soliris Prescribing Information (Published: July 2018).
The teachings of Finney et al. in view of the Clinical Trial Listing for NCT03052751 and as evidenced by International Nonproprietary Names for Pharmaceutical Substances as related to claim(s) 1, 5-16, 18-23, 27, and 28, from which these claims depend are given previously in this Office action and are fully incorporated here.
However, neither Finney et al. nor the Clinical Trial Listing for NCT03052751 teaches administering 4, 5, or 6 weekly doses followed by one or more additional doses that are lower dose and/or less frequency than the prior 4, 5, or 6 doses.
The Soliris Prescribing Information teaches the treatment of myasthenia gravis with another biologic, Soliris, also known as eculizumab, wherein the antibody is administered at 900mg weekly for 4 weeks, followed by 1200mg a week later, then 1200mg Q2W thereafter; see Abstract.
It would have been obvious to one of ordinary skill in the art to divide the treatment regimen of myasthenia gravis, a chronic disease requiring long-term treatment, into two phases: induction and maintenance similar to the regimen taught by the Soliris Prescribing Information. In the Soliris Prescribing Information, treatment begins with the antibody being administered at 900mg weekly for four weeks, followed by 1200mg at the fifth week, then the frequency is lengthened to once every two weeks maintenance dosing. One of ordinary skill in the art would have been motivated by market forces to have an induction phase of 5 doses given weekly followed by a maintenance phase of less frequent every two-week dosing as taught by the Soliris Prescribing Information. Prescribing physicians and patients with chronic disease are more likely to select therapies with more convenient long-term dosing regimens such as less frequent doses in a maintenance phase. The dosing regimen of biologic taught by the Soliris Prescribing Information is already FDA approved for the treatment of myasthenia gravis, thus, in order to a acquire a significant market share of patients already on Soliris, the long-term dosing regimen of the instant biologic must be at least as convenient as Soliris. Further, Finney et al. teaches that the anti-FcRn may be administered biweekly (see page 30 line 14), so one of ordinary skill in the art would have a reasonable expectation of success in modifying the dose frequency to every two weeks.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
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, 5-9, 10-16, 27, and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-11, 13, 16, and 17 of U.S. Patent No. 10,233,243 B2 in view of Finney et al. (WO 2014/019727 A1; Published: Feb 6, 2014) and the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) and as evidenced by International Nonproprietary Names for Pharmaceutical Substances (WHO Drug Information. 30(2): 241-357; Published: 2016).
Claims 1, 5-9, 10-16, 27, and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-11, 13, and 16 of U.S. Patent No. 11,384,148 B2 in view of Finney et al. (WO 2014/019727 A1; Published: Feb 6, 2014) and the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) and as evidenced by International Nonproprietary Names for Pharmaceutical Substances (WHO Drug Information. 30(2): 241-357; Published: 2016).
Claims 1, 5-9, 10-16, 27, and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7-9, 11, 12, 14-17, 20-22, 24, 25, 27-30, 34-36, 37, 38, 40-43, and 47-51 of U.S. Patent No. 12,338,285 B2 in view of Finney et al. (WO 2014/019727 A1; Published: Feb 6, 2014) and the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) and as evidenced by International Nonproprietary Names for Pharmaceutical Substances (WHO Drug Information. 30(2): 241-357; Published: 2016).
The following analysis applies to the rejections over the claims of U.S. Patent Nos. 10,233,243 B2; 11,384,148 B2; and 12,338,285 B2.
Regarding instant claim 1, issued claim 1 of U.S. Patent No. 10,233,243 B2 teaches a method of treating a patient having myasthenia gravis with an anti-FcRn antibody comprising CDRs having the sequences given in SEQ ID NOs 1-6, which are 100% identical to instant SEQ ID NOs: 1-6. Issued claims 1 and 16 of U.S. Patent No. 11,384,148 B2 teach the method of treating autoimmune diseases, including myasthenia gravis, with the anti-FcRn antibody comprising CDRs having the sequences given in SEQ ID NOs 1-6, which are 100% identical to instant SEQ ID NOs: 1-6. And copending claims 1, 14, 27, and 40 of Application No.17/804,934 teach the process and components needed to produce the anti-FcRn antibody comprising CDRs having the sequences given in SEQ ID NOs 1-6, which are 100% identical to instant SEQ ID NOs: 1-6. Similarly, regarding instant claims 6-8, issued claims 3 and 4 of U.S. Patent No. 10,233,243 B2, issued claims 3 and 4 of U.S. Patent No. 11,384,148 B2, and issued claims 3, 4, 16, 17, 29, 30, 42, and 43 of U.S. Patent No. 12,338,285 B2 teach that the anti-FcRn antibody comprises heavy and light variable chains comprising SEQ ID NOs: 29 and 15, respectively, which are 100% identical to instant SEQ ID NOs: 29 and 15; see claim 10. Additionally, regarding instant claim 11, issued claim 11 of U.S. Patent No. 10,233,243 B2, issued claim 11 of U.S. Patent No. 11,384,148 B2, and issued claims 9, 22 36, and 49 of U.S. Patent No. 12,338,285 B2 teaches that the anti-FcRn antibody comprises heavy and light chains comprising SEQ ID NOs: 72, 87, or 43, and 22, respectively, which are 100% identical to instant SEQ ID NOs: 72, 87, or 43, and 22; see claim 18. Regarding claim 12, the identifiers UCB7665 or rozanolixizumab, which are understood to be alternative identifiers for the same anti-FcRn antibody, are evidenced by the WHO Drug Information to refer to the anti-FcRn antibody comprising the heavy and light variable regions of SEQ ID NOs: 29 and 15 and the heavy and light chains having 100% identity through their length to SEQ ID NO: 43 and 22; see pages 309-310.
Further, regarding instant claims 5 and 10, issued claims 2, 9, and 10 of U.S. Patent No. 10,233,243 B2, issued claims 2, 9, and 10 of U.S. Patent No. 11,384,148 B2, and issued claims 2, 7, 8, 15, 20, 21, 28, 34, 35, 41, 47, and 48 of U.S. Patent No. 12,338,285 B2 teach that the anti-FcRn antibody is a humanized, full-length antibody selected from the group consisting of IgG1, IgG4, and IgG4P. Regarding instant claims 13 and 14, the anti-FcRn antibody has a binding affinity for human FcRn; see issued claims 13 and 14 of U.S. Patent No. 10,233,243 B2, issued claims 13 and 14 of U.S. Patent No. 11,384,148 B2, and issued claims 11, 12, 24, 25, 37, 38, 50, and 51 of U.S. Patent No. 12,338,285 B2. Further, regarding instant claims 15 and 16, the anti-FcRn antibody taught by U.S. Patent No. 10,233,243 B2 can be provided as a pharmaceutical composition and which further comprises one or more additional active ingredients; see issued claims 16 and 17 of U.S. Patent No. 10,233,243 B2.
The issued claims of U.S. Patent Nos. 10,233,243 B2; 11,384,148 B2; and 12,338,285 B2 do not teach doses or dosing regimens, the specific binding affinity of the anti-FcRn antibody, the route of administration, nor the characteristics of the patient to be treated for myasthenia gravis.
Regarding claim 1, 6-8, and 11, Finney et al. teaches a method of treating a patient having myasthenia gravis with an anti-FcRn antibody which comprises: 1. CDRs having the sequences given in SEQ ID NOs 1-6, which are 100% identical to instant SEQ ID NOs: 1-6; 2. heavy and light variable chains comprising SEQ ID NOs: 29 and 15, respectively, which are 100% identical to instant SEQ ID NOs: 29 and 15, and 3. heavy and light chains comprising SEQ ID NOs: 72, 87, or 43, and 22, respectively, which are 100% identical to instant SEQ ID NOs: 72, 87, or 43, and 22; see claims 1-8, 10, 18, 41, and 42. Regarding claim 12, the identifiers UCB7665 or rozanolixizumab, which are understood to be alternative identifiers for the same anti-FcRn antibody, are evidenced by the WHO Drug Information to refer to the anti-FcRn antibody comprising the heavy and light variable regions of SEQ ID NOs: 29 and 15 and the heavy and light chains having 100% identity through their length to SEQ ID NO: 43 and 22; see pages 309-310.
Further, regarding claims 5 and 10, the anti-FcRn antibody taught by Finney et al. is a humanized, full-length antibody selected from the group consisting of IgG1, IgG4, and IgG4P; see claims 9, 16, and 17. Regarding claims 13 and 14, the anti-FcRn antibody taught by Finney et al. has a binding affinity for human FcRn of 100pM or less when measures at pH6 - pH7.4; see claims 20 and 21. Further, regarding claims 15 and 16, the anti-FcRn antibody can be provided as a pharmaceutical composition and which further comprises one or more additional active ingredients; see claims 37 and 38.
Regarding the doses in claim 1, Finney et al. teaches that a therapeutically effective amount will be from 0.01 mg/kg to 500 mg/kg; see page 29 lines 20-21. Finney et al. Figures 9 and 12-16 teaches administering multiple doses of 20mg/kg to non-human primates. Additionally, Finney et al. Figures 20, 21, and 23 teach administering 10mg/kg to transgenic mice. Further, Figures 13 and 16 teach administering 4 or 10 repeat doses. Regarding claim 22, Finney et al. teaches that the anti-FcRn antibody can be administered subcutaneously or intravenously; see page 31 lines 23-25.
Regarding weekly dosing, Examples 7 and 8 demonstrate that IgG levels reach the lowest point at day 7 following administration and begin to rise thereafter. Further, Finney et al. teaches possible repeat dosing to achieve long-term maintenance of low plasma IgG concentration; see page 25 line 19-20.
Finney et al. does not teach the use of the anti-FcRn for the treatment of generalized myasthenia gravis classified as moderate to severe or in patients with anti-AChR or anti-MuSK antibody-positive disease, nor that additional doses following doses 4, 5, or 6 weekly doses are administered at lower and/or less frequent doses.
Regarding claims 1, 27, and 28, the Clinical Trial Listing for NCT03052751 teaches treating human patients with generalized myasthenia gravis who are classified as moderate to severe with the anti-FcRn antibody, UCB7665; see Study Description: Brief Summary. Further, the clinical trial listing teaches treating humans with anti-AChR and/or anti-MuSK antibody-positive disease; see Inclusion Criteria.
It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat human patients with moderate to severe, generalized myasthenia gravis with the anti-FcRn antibody taught by the issued claims of U.S. Patent Nos. 10,233,243 B2; 11,384,148 B2; and 12,338,285 B2 – which is identical to the antibody taught by Finney et al. - because the issued claims of U.S. Patent No. 11,384,148 B2 and Finney et al. teaches that the anti-FcRn antibody can be used to treat myasthenia gravis and the Clinical Trial Listing for NCT03052751 teaches using the same antibody to treat moderate to severe, generalized myasthenia gravis.
Regarding doses and frequency, it would have been obvious to one of ordinary skill in the art that patients having myasthenia gravis, a chronic disease, would benefit from weekly and long-term maintenance doses. One would be motivated to treat weekly because Finney et al. exemplifies weekly dosing and plasma IgG levels were demonstrated to reached the lowest point at day 7 following administration. The teaching that plasma IgG levels reach the lowest concentration at day 7, would have given one of ordinary skill in the art a reasonable expectation of success at maintaining low plasma IgG levels when administered on a weekly schedule.
It would have been obvious to one of ordinary skill in the art to use the dosing and frequency schedules and route of administration taught by Finney et al. as starting points for optimization by routine experimentation. Indeed, Finney et al. teaches that dosing and frequency schedules demonstrated in animal models may be useful for determining the dosing and routes of administration in humans and that the therapeutically effective amount may be determined by routine experimentation; see page 29 lines 11-15 and 19-20. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claim 25 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-11, 13, 16, and 17 of U.S. Patent No. 10,233,243 B2 in view of Finney et al. (WO 2014/019727 A1; Published: Feb 6, 2014) and the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) and as evidenced by International Nonproprietary Names for Pharmaceutical Substances (WHO Drug Information. 30(2): 241-357; Published: 2016) as applied to claim(s) 1, 5-16, 18-23, 27, and 28 above, and further in view of the Soliris Prescribing Information (Published: July 2018).
Claim 25 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-11, 13, and 16 of U.S. Patent No. 11,384,148 B2 in view of Finney et al. (WO 2014/019727 A1; Published: Feb 6, 2014) and the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) and as evidenced by International Nonproprietary Names for Pharmaceutical Substances (WHO Drug Information. 30(2): 241-357; Published: 2016) as applied to claim(s) 1, 5-16, 18-23, 27, and 28 above, and further in view of the Soliris Prescribing Information (Published: July 2018).
Claim 25 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7-9, 11, 12, 14-17, 20-22, 24, 25, 27-30, 34-36, 37, 38, 40-43, and 47-51 of U.S. Patent No. 12,338,285 B2 in view of Finney et al. (WO 2014/019727 A1; Published: Feb 6, 2014) and the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) and as evidenced by International Nonproprietary Names for Pharmaceutical Substances (WHO Drug Information. 30(2): 241-357; Published: 2016) as applied to claim(s) 1, 5-9, 10-16, 27, and 28 above, and further in view of the Soliris Prescribing Information (Published: July 2018).
The following analysis applies to the rejections over the claims of U.S. Patent Nos. 10,233,243 B2; 11,384,148 B2; and 12,338,285 B2. The teachings of the claims of U.S. Patent Nos. 10,233,243 B2; 11,384,148 B2; and 12,338,285 B2 in view of Finney et al. and the Clinical Trial Listing for NCT03052751 and as evidenced by International Nonproprietary Names for Pharmaceutical Substances as related to claim(s) 1, 5-16, 18-23, 27, and 28, from which these claims depend are given previously in this Office action and are fully incorporated here.
However, neither the claims of U.S. Patent Nos. 10,233,243 B2; 11,384,148 B2; and 12,338,285 B2, Finney et al. nor the Clinical Trial Listing for NCT03052751 teaches administering 4, 5, or 6 weekly doses followed by one or more additional doses that are lower dose and/or less frequency than the prior 4, 5, or 6 doses.
The Soliris Prescribing Information teaches the treatment of myasthenia gravis with another biologic, Soliris, also known as eculizumab, wherein the antibody is administered at 900mg weekly for 4 weeks, followed by 1200mg a week later, then 1200mg Q2W thereafter; see Abstract.
It would have been obvious to one of ordinary skill in the art to divide the treatment regimen of myasthenia gravis, a chronic disease requiring long-term treatment, into two phases: induction and maintenance similar to the regimen taught by the Soliris Prescribing Information wherein the antibody taught by the claims of U.S. Patent Nos. 10,233,243 B2; 11,384,148 B2; and 12,338,285 B2 is administered. In the Soliris Prescribing Information, treatment begins with the antibody being administered at 900mg weekly for four weeks, followed by 1200mg at the fifth week, then the frequency is lengthened to once every two weeks maintenance dosing. One of ordinary skill in the art would have been motivated by market forces to have an induction phase of 5 doses given weekly followed by a maintenance phase of less frequent every two-week dosing as taught by the Soliris Prescribing Information. Prescribing physicians and patients with chronic disease are more likely to select therapies with more convenient long-term dosing regimens such as less frequent doses in a maintenance phase. The dosing regimen of a biologic taught by the Soliris Prescribing Information is already FDA approved for the treatment of myasthenia gravis, thus, in order to acquire a significant market share of patients already on Soliris, the long-term dosing regimen of the instant biologic must be at least as convenient as Soliris. Further, Finney et al. teaches that the anti-FcRn may be administered biweekly (see page 30 line 14), so one of ordinary skill in the art would have a reasonable expectation of success in modifying the dose frequency to every two weeks.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Response to Arguments
Applicant’s arguments filed June 8, 2026 have been considered, but are not persuasive.
On pages 6-7, Applicant argues against routine optimization as an avenue to identifying the claimed doses and intervals of the anti-FcRN antibody. Applicant cites MPEP 2144.05 (III)(D); this section is reproduced below (emphasis added):
One factor that may weigh against maintaining an obviousness rejection based on optimization of a variable disclosed in a range in the prior art is where an applicant establishes that the prior art disclosure of the variable is within a range that is so broad in light of the dissimilar characteristics of the members of the range as to not invite optimization by one of skill in the art. Genetics Inst., LLC v. Novartis Vaccines & Diagnostics, Inc., 655 F.3d 1291, 1306, 99 USPQ2d 1713, 1725 (Fed. Cir. 2011) (holding that ordinary motivation to optimize did not apply where disclosure was 68,000 protein variants including 2,332 amino acids where one of skill in the art would appreciate that the claimed truncated proteins vary enormously in structure). See MPEP §§ 2131.02, 2131.03, and 2144.08 for additional discussion on consideration of range limitations.
This section discusses modifying thousands of protein structures, not determining the optimum dosing regimen of a single therapeutic. The members of the range in the example in the MPEP are the thousands of protein variants including thousands of amino acids, wherein varying the protein structures confer varying characteristics. In contrast, Finney et al. teaches an overlapping range of doses and intervals of a single agent. And Finney et al. provides guidance to direct the routine optimization towards the instantly claimed doses and intervals; see the rejection under 35 U.S.C. 103.
Additionally, Applicant cites MPEP 2145(X)(B) which cautions against the obvious to try rationale where “the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful.” This argument is contrary to the facts of this case, Finney et al. provides an enabling disclosure teaching dose optimization in non-human primates; see Examples 7 and 8, for example. The optimization of the dosage regimen of a known drug, especially based on the non-human primate data provided in Finney et al., is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made
Applicant argues, on pages 8-9, that the Office “has not properly established that the cited art provides a basis to predict that an FcRn inhibitor, which reduces total IgG, would be equally or more effective in MuSK patients where the pathogenic antibodies are IgG4, a subclass with distinct recycling kinetics”
It is the position of the Office that based on the inclusion criteria of Clinical Trial Listing for NCT03052751, which specifically calls out both anti-MuSK patients and anti-AChR patients, it would have been obvious to one of ordinary skill in the art to treat patients with either anti-MuSK or anti-AChR antibodies.
Applicant states that the Office has misinterpreted MPEP 2107.03 IV; provided below. Applicant states that this section refers to utility and not obviousness.
MPEP 2107.03 IV states:
Before a drug can enter human clinical trials, the sponsor, often the applicant, must provide a convincing rationale to those especially skilled in the art (e.g., the Food and Drug Administration (FDA)) that the investigation may be successful. Such a rationale would provide a basis for the sponsor’s expectation that the investigation may be successful. In order to determine a protocol for phase I testing, the first phase of clinical investigation, some credible rationale of how the drug might be effective or could be effective would be necessary. Thus, as a general rule, if an applicant has initiated human clinical trials for a therapeutic product or process, Office personnel should presume that the applicant has established that the subject matter of that trial is reasonably predictive of having the asserted therapeutic utility.
This section is clear that – as a general rule – “if an applicant has initiated human clinical trials for a therapeutic product or process, Office personnel should presume that the applicant has established that the subject matter of that trial is reasonably predictive of having the asserted therapeutic utility.”
Thus, because the inclusion criteria specifically lists both anti-MuSK patients and anti-AChR patients in an initiated human trial, one of ordinary skill in the art would have had a reasonable expectation of success treating both patients having anti-MuSK antibodies and patients having anti-AChR antibodies by administering the anti-FcRn antibody as claimed.
On pages 7-9, Applicant argues unexpected results based on data provided in a post-filing non-patent literature, but no Declaration was filed to accompany the allegations of unexpected results. MPEP 716.01(c), “[t]o be of probative value, any objection evidence should be supported by actual proof. Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See, for example, In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984) (“It is well settled that unexpected results must be established by factual evidence.” The evidence, while allegedly probative, is not properly filed in an affidavit or declaration. Therefore, the potential probative value of the evidence is not supported by the manner of Applicant’s submission.
More specifically regarding the lack of a declaration or affidavit, the arguments presented here are lacking 1. A comparison to the prior art and 2. An explanation as to why these findings in Bril et al. 2023 are allegedly unexpected; see MPEP 716.02(b) and 716.02(e).
The rejection of record relies up Finney et al. which teaches the anti-FcRn antibody comprising SEQ ID NOs: 1-6; see claims 1-8 for example. Finney et al. teaches treating myasthenia gravis and provides a range of doses, even exemplifying weekly dosing; see claims 40 and 42 and Figures 12-18 for example. The Clinical Trial Listing for NCT03052751 further supports treating moderate to severe generalized myasthenia gravis and teaches treating both anti-MuSK and anti-AChR patients.
On pages 7-8, Applicant discusses an endpoint metric called “MG Symptoms PRO” as related to unexpected results. Applicant states that the findings of this “MG Symptoms PRO” endpoint are not reflective of another endpoint metric called “MG-ADL score”. Applicant states that “the MG Symptoms PRO measures dimension of disease burden, particularly physical fatigue, that are absent from the endpoints use in the cited art” and, thus, the rejection under 35 U.S.C. 103 should be withdrawn.
First, the instantly claimed invention is to a method of treating comprising only a step of administering. There is no requirement to measure by this MG Symptoms PRO endpoint.
Further, Bril et al. 2023 provides a comparison of the mean change by MG-ADL, MGC, and QMG endpoint metrics in the top row of figure 2 compared to by MG Symptom PRO metrics in the bottom row. Figure 2 is reproduced below for convenience. The trends relative to placebo between the various metrics appear consistent.
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The findings regarding MG Symptoms PRO score and physical fatigue appear to demonstrate that the anti-FcRn antibody was effective at treating myasthenia gravis as evidenced by the reported symptom improvement. Both Finney et al. and NCT03052751 teach treating myasthenia gravis with the anti-FcRn antibody, thus the finding of improved symptoms is expected. There is no explanation as to why measuring with this new MG Symptoms PRO metric and finding that the anti-FcRn antibody reduced that symptoms of the disease it is taught to treat would be unexpected.
Additionally, Applicant alleges that the findings in anti-MuSK patients are unexpected. On page 8, Applicant reasons that because the anti-FcRn antibody reduces total IgG, it is unexpected that it would work on both patients with anti-AChR antibodies and anti-MuSK antibodies because anti-AChR antibodies are IgG1 and IgG3 autoantibodies and anti-MuSK antibodies are IgG4 autoantibodies. Applicant alleges that the IgG4 subclass has distinct recycling kinetics, but does not provide evidence.
Applicant points to the least square means reductions among anti-MuSK patients which demonstrate that anti-MuSK patients treated with the anti-FcRn antibody achieved a better reduction of symptoms relative to patients treated with placebo. However, one would expect this given that the NCT03052751 listing taught treating anti-MuSK patients. It is unclear what Applicant considers to be unexpected about this finding.
Moreover, if the alleged unexpected result is in patients with anti-MuSK antibodies, then to be commensurate in scope with the alleged unexpected results, the independent claim must recite anti-MuSK antibody-positive patients. Then, on page 9, Applicant argues that it is unexpected that the anti-FcRn antibody – despite listing both patient populations in the initiated clinical trial listing – that the claimed regimen has efficacy across the entire generalized MG population. Again, it is unclear what exactly Applicant considers unexpected regarding anti-AChR and anti-MuSK patients in Bril et al. 2023. The NCT03052751 taught treating both anti-AChR and anti-MuSK patients and according to Bril et al. 2023, the treatment taught to work in both groups of patients, as one would expect, did work in both groups of patients.
Regarding that NSDP rejections, Applicant argues that the claims in U.S. Patent Nos. 10,233,243 and 11,384,148 and Application No. 17/804,934 recite products or a method of treating autoimmune diseases in general and that issued claims do not cure the alleged deficiencies of the secondary references (Finney et al. and the Clinical Trial Listing of NCT03052751), also cited in the rejections under 35 U.S.C. 103. This argument is unpersuasive for the same reasons as above.
The rejection under 35 U.S.C. 112b was resolved by amendment.
The rejections under 35 U.S.C. 103 and on the ground of nonstatutory double patenting are maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Atherfold et al. (WO 2015/071330 A1; Published: May 21, 2015) teaches anti-FcRn antibodies for the treatment of autoimmune diseases, including myasthenia gravis.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/KATHERINE ANN HOLTZMAN/Examiner, Art Unit 1646 /JULIET C SWITZER/Primary Examiner, Art Unit 1682
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