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 .
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 § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10, which has been amended to depend from claim 1, recites the limitation “the full length antibody” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not recite “the full length antibody”. It is unclear whether “the full length antibody” of claim 10 refers to the anti-FcRn antibody of claim 1. For the purpose of compact prosecution, “the full length antibody” is interpreted as referring to the anti-FcRn antibody, consist with the definition on page 7 of the instant Specification. Amending claim 10 to recite “wherein the anti-FcRn antibody is a full length antibody selected from the group consisting of an IgG1, IgG4 and IgG4P.” would remedy the indefiniteness.
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 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 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 provisionally 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 copending Application No. 17/804,934 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).
This is a provisional nonstatutory double patenting rejection.
The following analysis applies to the rejections over the claims of U.S. Patent Nos. 10,233,243 and 11,384,148 B2 and copending Application No.17/804,934.
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 copending claims 3, 4, 16, 17, 29, 30, 42, and 43 of Application No.17/804,934 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 copending claims 9, 22 36, and 49 of Application No.17/804,934 teaches that the anti-FcRn antibody tcomprises 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 copending claims 2, 7, 8, 15, 20, 21, 28, 34, 35, 41, 47, and 48 of Application No.17/804,934 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 copending claims 11, 12, 24, 25, 37, 38, 50, and 51 of Application No.17/804,934. 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 and 11,384,148 B2, and the copending claims of Application No. 17/804,934 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 and 11,384,148 B2, and the copending claims of Application No. 17/804,934 – 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 provisionally 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 copending Application No.17/804,934 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).
This is a provisional nonstatutory double patenting rejection.
The following analysis applies to the rejections over the claims of U.S. Patent Nos. 10,233,243 and 11,384,148 B2 and copending Application No.17/804,934.
The teachings of the claims of U.S. Patent Nos. 10,233,243 and 11,384,148 B2 and copending Application No.17/804,934 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 and 11,384,148 B2 and copending Application No.17/804,934, 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 and 11,384,148 B2 and copending Application No.17/804,934 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 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.
Response to Arguments
The declaration under 37 C.F.R. 1.132 from Nicole Domin filed August 22, 2025 has been considered. It is understood that the declaration states that the UCB (PROTOCOL MG0002, ClinicalTrials.gov identifier: NCT03052751) document, shown by the arrow in the screenshot of the NCT03052751 listing below, was not actually posted on September 17, 2017.
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Recall that following the declaration under 37 C.F.R. 1.132 from Nicole Domin filed October 30, 2024 the rejections supported by UCB (PROTOCOL MG0002, ClinicalTrials.gov identifier: NCT03052751) were withdrawn and new rejections citing the Clinical Trial Listing for NCT03052751 – the ClinicalTrials.gov website – were made.
The rejections supported by the Clinical Trial Listing for NCT03052751 (ClinicalTrials.gov; Published: Sept 27, 2017) reference the actual ClinicalTrials.gov website – not the “Study Protocol” document, also referred to as UCB (PROTOCOL MG0002, ClinicalTrials.gov identifier: NCT03052751).
The clinical trial listing cited in the rejection, while noted in the statement of rejection as published September 27, 2017 was actually published September 28, 2017 – September 27, 2017 is the submission date; see the screenshot below. Regardless, both September 27 and 28, 2017 precede the effective filing date. Applicant has provided no evidence refuting the publication of the Clinical Trial Listing as a whole. Evidence provided by Applicant appears limited to the publication of the UCB (PROTOCOL MG0002, ClinicalTrials.gov identifier: NCT03052751) document or called the “Study Protocol” document as highlighted in the screenshot above.
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For clarity, the rejection references the Study Description section which teaches the treatment of moderate to severe myasthenia gravis; see the screenshot below.
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Additionally, the rejection relies on the inclusion criteria which teaches that both anti-AChR and anti-MuSK positive patients; see the screenshot below.
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Accordingly, the rejections do not rely on the UCB (PROTOCOL MG0002, ClinicalTrials.gov identifier: NCT03052751), which is understood to be the linked “Study Protocol” document shown in the screenshot on page 18 of this action. Thus, there is no rejection to be withdrawn by the declaration filed August 22, 2025 because no rejection relies on the UCB (PROTOCOL MG0002, ClinicalTrials.gov identifier: NCT03052751) document, also called the “Study Protocol”.
Applicant’s arguments filed August 22, 2025 have been considered, but are not persuasive.
Applicant argues that Finney et al. teaches a wide range of therapeutic amounts and many routes of administration, and that to reach the combination of subcutaneous 7mg/kg or 10mg/kg administered weekly would require improper hindsight. The Office disagrees. Optimal dosing schedules and routes of administration are determined through routine optimization and, indeed, Finney et al. teaches the use of optimization through routine experimentation to determine therapeutically effective amount the anti-FcRn antibody for a human subject based on a variety of factors including time and frequency of administration; see page 29 lines 11-15 and 19-20.
Applicant argues that regarding Example 7 and weekly dosing, the example demonstrates the effect of an antibody fragment and not a full-length antibody. For Example 7, this is true. However, Finney et al. Example 8 teaches the benefit of 7-day dosing using a full-length antibody – IgG4P.
Applicant argues that efficacy demonstrated in Bril et al. (Lancet Neurology. 22(5): 383-394; Published: May 2023) wherein the anti-FcRn antibody is effective in both patients with anti-MuSK and anti-AChR antibodies is an unexpected result. The Office disagrees. The Clinical Trial Listing NCT03052751 inclusion criteria calls out the inclusion of both patients with anti-MuSK or anti-AChR antibodies.
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.
Thus, by the explicit listing of anti-MuSK positive patients in the inclusion criteria, it would have been obvious to one of ordinary skill in the art to treat both anti-AChR or anti-MuSK positive patients and one would have had a reasonable expectation of success to treat both patient populations with the anti-FcRn antibody. Efficacy in both patient populations is not unexpected.
Further, claim 1 is generic to any patient with myasthenia gravis regardless of autoantibody type and claim 28, as written in the alternative, does not require the patient be anti-MuSK positive. The scope of the claims is not commensurate with the alleged unexpected result.
Note that while Bril et al. (Lancet Neurology. 22(5): 383-394; Published: May 2023) is referenced by Applicant, no copy was filed. While not relied upon for any rejection, the reference is included with this action in interest of compact prosecution.
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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 /DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644