DETAILED ACTION
Claims 1-3, 5-6, 8-9, 11, 13-21, 43-46, and 51 are pending in the instant application and being examined on the merit.
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 .
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Examples of references in the specification that relate to the instant invention are below:
Kusner, L et al; Casadevall, N et al (page 41);
Lee et al (page 44);
Howard, J et al (page 56);
Fitzpatrick, A et al (page 57);
Rondeau et al (page 68);
Posner, K et al (page 76);
Little, R and Yau, L; O’Kelley M RB (page 85); and
Pittock, N; Hillmen et al, Legendre, N; Howard et al; Benatar et al (page 90), etc.
Claim Rejections - 35 USC § 112(b)
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.
Claims 5-6, 8-9, and 43-46 are 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.
Instant claims 5, 8, 43, and 45 recite exemplary language that renders the claim indefinite because it is unclear whether the limitation is part of the claimed invention. Specifically, the limitation in the parentheses “(reduction)” renders the claim indefinite in regards to instant claims 5, 8, 43, and 45, because it is unclear whether the limitation in the parenthesis is part of the claimed invention. Claims 6, 9, 44, and 46 depend on claims 5, 8, 43, and 45, respectively, and therefore also indefinite.
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 (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.
(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 1-3, 5-6, 8-9, 11, 13, 20-21, 43-46, and 51 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Bedrosian et al (US20170342139A1, Priority to May 27, 2016, Published on November 30 2017; hereinafter Bedrosian).
Regarding instant claims 1, 2, and 13, Bedrosian teaches methods of treating refractory generalized myasthenia gravis (MG) in a patient in need thereof comprising administering a therapeutically effective amount of an anticomplement component 5 (C5) antibody or an antigen binding fragment thereof to the patient, wherein the patient is administered the anti-C5 antibody or antigen binding fragment thereof for at least 26 weeks (page 23, ¶ [0005]). Bedrosian also teaches that the anti-C5 antibody is an eculizumab variant, BNJ441 (also known as ALXN1210 or ravulizumab, hereinafter ravulizumab), engineered to have a longer half-life in humans, wherein ravulizumab comprises (i) a VH region comprising the amino acid sequence set forth in SEQ ID NO:12 comprising HCDR1, HCDR2, and HCDR3 domains having the sequences set forth in SEQ ID NOs:19, 18, and 3, respectively; and (ii) a VL region comprising the amino acid sequence set forth in SEQ ID NO:8 comprising LCDR1, LCDR2, and LCDR3 domains having the sequences set forth in SEQ ID NOs:4, 5, and 6, respectively (pages 27-28, ¶ [0062]-[0063]; page 60, ¶ [0530]). SEQ ID NOs:3-6,18, and 19 are identical to instant SEQ ID NOs:3-6, 18, and 19 recited in instant claim 1. Furthermore, Bedrosian teaches that the first sign of improvement occurs at week 1 after ravulizumab administration, wherein MG Activities of Daily Living Profile (MG-ADL) was performed and QMG was administered at week 1 (page 34, ¶ [0095]-[0096]; page 50, ¶ [0410]).
Regarding instant claim 3, Bedrosian teaches that refractory generalized MG is characterized as including subjects or patients positive for auto-antibodies binding to nicotinic acetylcholine receptor (anti-AChR) (page 29, ¶ [0078]-[0079]).
Regarding instant claims 5 and 6, Bedrosian teaches that the patient being treated by the anti-C5 antibody, e.g. ravulizumab, experiences a clinically meaningful improvement (reduction) in MG-ADL score after 26 weeks of treatment, wherein the clinically meaningful improvement the patient experiences is at least a 3 point reduction in the patient’s MG-ADL score after 26 weeks of treatment (page 24, ¶ [0012]).
Regarding instant claims 8 and 9, Bedrosian teaches that the patient being treated by the anti-C5 antibody, e.g. ravulizumab, experiences a clinically meaningful improvement (reduction) in quantitative Myasthenia Gravis score (QMG) after 26 weeks of treatment, wherein the clinically meaningful improvement the patient experiences is at least a 4 point reduction in the patient's QMG score after 26 weeks of treatment (page 24, ¶ [0013]).
Regarding instant claim 11, Bedrosian teaches that the first sign of improvement is maintained at least 26 weeks (page 34, ¶ [0096]).
Regarding instant claim 20, Bedrosian teaches that ravulizumab is administered intravenously (page 28, ¶ [0072]).
Regarding claims 21 and 51, Bedrosian teaches that subjects who have received previous treatment with eculizumab are part of the subject exclusion criteria (page, ¶ [0352] of §2.2 Subject Exclusion Criteria). Furthermore, Bedrosian teaches that eculizumab is a humanized monoclonal antibody that is a terminal complement inhibitor (page 27, ¶ [0059]).
Regarding instant claims 43 and 44, the teachings of Bedrosian are discussed above (see discussions for instant claims 1-3 and 5-6). Furthermore, Bedrosian teaches that the MG-ADL entry criteria are those who had a MG-ADL total score greater or equal to 6 (page 46, ¶ [0319]).
Regarding instant claims 45 and 46, the teachings of Bedrosian are discussed above (see discussions for instant claims 1-3, 8-9, and 43-44).
Claims 1-2, 11, 14-21, and 51 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Shafner (WO2019084438A1, Priority to June 15, 2018, Published on May 2, 2019; hereinafter Shafner).
Regarding claims 1 and 2, Shafner teaches methods for treating MG in a human patient, comprising administering to the patient an anti-C5 antibody, or antigen binding fragment thereof, wherein the anti-C5 antibody, or antigen binding fragment thereof, is administered according to a particular clinical dosage regimen, wherein the anti-C5 antibody is ravulizumab (also known as Ultomiris™, ALXN1210 and antibody BNJ441) comprising (i) the CDR1, CDR2, and CDR3 domains of the heavy chain variable (VH) region of ravulizumab having the sequence shown in SEQ ID NO: 12, wherein the CDR1, CDR2 and CDR3 heavy chain sequences comprise the amino acid sequences set forth in SEQ ID NOs:19, 18, and 3, respectively; and (ii) the CDR1, CDR2 and CDR3 domains of the light chain variable (VL) region of ravulizumab having the sequence shown in SEQ ID NO:8, wherein the CDR1, CDR2 and CDR3 light chain sequences comprise the amino acid sequences as set forth in SEQ ID NOs:4, 5, and 6, respectively (page 4, lines 12-31; page 16, line 15-page 17, line 2). SEQ ID NOs:3-6,18, and 19 are identical to instant SEQ ID NOs:3-6, 18, and 19 recited in instant claim 1. Shafner furthermore teaches that the treatment effect, e.g. LDH levels, were observed at week 1 after the initiation of the treatment (FIGs. 9, 11-14, 20-23)
Regarding instant claims 11, and 14-19, Shafner teaches in page 8, lines 12-26 and FIG. 26 of the disclosure that the anti-C5 antibody, or antigen binding fragment thereof, is administered to:
a patient weighing > 40 to < 60 kg (see instant claims 14):
once on Day 1 of the administration cycle at a dose of 2400 mg; and
on Day 15 of the administration cycle and every eight weeks thereafter at a dose of 3000 mg; or
a patient weighing > 60 to < 100 kg (see instant claims 16):
once on Day 1 of the administration cycle at a dose of 2700 mg; and
on Day 15 of the administration cycle and every eight weeks thereafter at a dose of 3300 mg; or
a patient weighing > 100 kg (see instant claims 18):
once on Day 1 of the administration cycle at a dose of 3000 mg; and
on Day 15 of the administration cycle and every eight weeks thereafter at a dose of 3600 mg.
Shafner also teaches that ravulizumab is administered for one or more administration cycles, wherein the administration cycle is 26 weeks (see instant claim 11). Furthermore, Shafner discloses that ravulizumab is administered once on Day 1 of the administration cycle, once on Day 15 of the administration cycle, and every eight weeks thereafter, and further administered every eight weeks after the administration cycle for an extension period up to two years (e.g., at a dose of 3000 mg, 3300 mg, or 3600 mg) (page 7, lines 3-10).
Regarding instant claim 20, Shafner teaches that the anti-C5 antibodies, e.g. ravulizumab, are formulated for intravenous administration (page 13, lines 1-3).
Regarding instant claims 21 and 51, Shafner teaches that the patient has not previously been treated with a complement inhibitor (e.g. eculizumab) (page 8, lines 27-28; page 67, lines 16-18).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 5-9, 11, 13, 20-21, and 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-17 of U.S. Patent No. 9,371,377B2 (Andrien et al, Priority to March 7, 2014; hereinafter ‘377).
claims 1-10 of U.S. Patent No. 9,663,574B2 (Andrien et al, Priority to March 7, 2014, hereinafter ‘574).
in view of Bedrosian et al (US20170342139A1, Priority to May 27, 2016, Published on November 30 2017; hereinafter Bedrosian). Although the claims at issue are not identical, they are not patentably distinct from each other.
The patented claims are directed to an isolated antibody, or antigen-binding fragment thereof, that comprises (i) a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:23, (ii) a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:19, (iii) a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, (iv) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, (v) a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and (vi) a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6; wherein, the isolated antibody, or antigen-binding fragment thereof described above comprises a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:11, wherein the heavy chain comprises the heavy chain variable region depicted in SEQ ID NO:12 and the light chain comprises the light chain variable region depicted in SEQ ID NO:8. The amino acid sequence SEQ ID NOs:8, 11, 12, and 14 are sequences of the BNJ441 antibody (also known as ravulizumab), which comprise HCDR1-3 comprising amino acid sequences SEQ ID NOs:23, 19, and 3, respectively, and LCDR1-3 comprising amino acid sequence SEQ ID NOs:4-6, respectively. SEQ ID NOs: 3-6, 8, 11-12, and 14 are identical to instant SEQ ID NOs:3-6, 8, 11-12, and 14, respectively. SEQ ID NOs: 23 and 19 are identical to instant SEQ ID NOs:19 and 18, respectively. The patented claims also recite a pharmaceutical composition comprising the antibody, or antigen binding fragment thereof, of that described above, and a pharmaceutically acceptable carrier (see claim 10 of ‘377 and claim 9 of ‘574).
However, ‘377 and ‘574 do not teach a method of treating a human patient with MG, the method comprising administering BNJ441 (ravulizumab) to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment.
The deficiency is resolved by Bedrosian.
The teachings of Bedrosian are discussed above in the 102 rejection.
Regarding instant claims 1, 2, and 13, it would have been obvious for a person having ordinary skill in the art at the time of filing to combine the method of treating a human patient with generalized MG of Bedrosian with the antibody BNJ441 of ‘377 or ‘574 to form a method of treating a human patient with generalized MG comprising administering ravulizumab to the patient. This is obvious because, ‘377 and ‘574 teach the antibody BNJ441 (ravulizumab) comprising a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:11, wherein the heavy chain comprises the heavy chain variable region depicted in SEQ ID NO:12 and the light chain comprises the light chain variable region depicted in SEQ ID NO:8, and Bedrosian teaches methods of treating refractory generalized MG in a patient in need thereof comprising administering a therapeutically effective amount of an anticomplement component 5 (C5) antibody or an antigen binding fragment thereof to the patient, wherein the anticomplement C5 antibody is ravulizumab and treatment is observed as early as week 1 after initiation of treatment. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method for treating a human patient with MG, the method comprising administering ravulizumab to the patient, wherein ravulizumab comprises CDRH1-H3 comprising the amino acid sequences SEQ ID NOs:19, 18, and 3, respectively, and CDRL1-L3 comprising the amino acid sequences SEQ ID NOs:4-6, respectively, and wherein the treatment effect is observed at week 1 after initiation of treatment.
Regarding instant claims 5 and 6, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the method of treating a human patient with generalized MG comprising administering ravulizumab to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment as taught by the combined teachings of ‘377, ‘574, and Bedrosian to comprise that the treatment results in the reduction in MG-ADL score of at least 3.0 after 26 weeks as taught by Bedrosian. This is obvious because, the combined teachings of ‘377, ‘574, and Bedrosian teach a method of treating a human patient with refractory generalized MG comprising administering ravulizumab comprising a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:11 to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment, and Bedrosian teaches that the patient being treated by the anti-C5 antibody, e.g. ravulizumab, experiences a clinically meaningful improvement (reduction) in MG-ADL score after 26 weeks of treatment, wherein the clinically meaningful improvement the patient experiences is at least a 3 point reduction in the patient’s MG-ADL score after 26 weeks of treatment. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method for treating a human patient with MG, the method comprising administering ravulizumab to the patient, wherein:
ravulizumab comprises CDRH1-H3 comprising the amino acid sequences SEQ ID NOs:19, 18, and 3, respectively, and CDRL1-L3 comprising the amino acid sequences SEQ ID NOs:4-6, respectively;
the instant treatment effect is observed at week 1 after initiation of treatment; and
the instant treatment results in the patient experiencing a reduction in the MG-ADL score after 26 weeks wherein the reduction is at least 3.0.
Regarding instant claims 8 and 9, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the method of treating a human patient with generalized MG comprising administering ravulizumab to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment as taught by the combined teachings of ‘377, ‘574, and Bedrosian to comprise that the treatment results in the reduction in QMG score of at least 4.0 after 26 weeks as taught by Bedrosian. This is obvious because, the combined teachings of ‘377, ‘574, and Bedrosian teach a method of treating a human patient with refractory generalized MG comprising administering ravulizumab comprising a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:11 to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment, and Bedrosian teaches that the patient being treated by the anti-C5 antibody, e.g. ravulizumab, experiences a clinically meaningful improvement (reduction) in quantitative Myasthenia Gravis score (QMG) after 26 weeks of treatment, wherein the clinically meaningful improvement the patient experiences is at least a 4 point reduction in the patient's QMG score after 26 weeks of treatment. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method for treating a human patient with MG, the method comprising administering ravulizumab to the patient, wherein:
ravulizumab comprises CDRH1-H3 comprising the amino acid sequences SEQ ID NOs:19, 18, and 3, respectively, and CDRL1-L3 comprising the amino acid sequences SEQ ID NOs:4-6, respectively;
the instant treatment effect is observed at week 1 after initiation of treatment; and
the instant treatment results in the patient experiencing a reduction in the QMG score after 26 weeks wherein the reduction is at least 2.8.
Regarding instant claim 11, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the method of treating a human patient with generalized MG comprising administering ravulizumab to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment as taught by the combined teachings of ‘377, ‘574, and Bedrosian to comprise that the treatment effect is maintained through week 26 after initiation of treatment as taught by Bedrosian. This is obvious because, the combined teachings of ‘377, ‘574, and Bedrosian teach a method of treating a human patient with refractory generalized MG comprising administering ravulizumab comprising a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:11 to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment, and Bedrosian teaches that the first sign of improvement is maintained at least 26 weeks. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method for treating a human patient with MG, the method comprising administering ravulizumab to the patient, wherein:
ravulizumab comprises CDRH1-H3 comprising the amino acid sequences SEQ ID NOs:19, 18, and 3, respectively, and CDRL1-L3 comprising the amino acid sequences SEQ ID NOs:4-6, respectively;
the instant treatment effect is observed at week 1 after initiation of treatment; and
the instant treatment effect is maintained through week 26 after initiation of treatment.
Regarding instant claim 20, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the method of treating a human patient with generalized MG comprising administering ravulizumab to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment as taught by the combined teachings of ‘377, ‘574, and Bedrosian to comprise that ravulizumab is administered intravenously as taught by Bedrosian. This is obvious because, the combined teachings of ‘377, ‘574, and Bedrosian teach a method of treating a human patient with refractory generalized MG comprising administering ravulizumab comprising a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:11 to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment, and Bedrosian teaches that ravulizumab is administered intravenously. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method for treating a human patient with MG, the method comprising administering ravulizumab intravenously to the patient, wherein ravulizumab comprises CDRH1-H3 comprising the amino acid sequences SEQ ID NOs:19, 18, and 3, respectively, and CDRL1-L3 comprising the amino acid sequences SEQ ID NOs:4-6, respectively, and wherein the instant treatment effect is observed at week 1 after initiation of treatment.
Regarding instant claims 21 and 51, it would have been obvious for a person having ordinary skill in the art at the time of filing to modify the method of treating a human patient with generalized MG comprising administering ravulizumab to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment as taught by the combined teachings of ‘377, ‘574, and Bedrosian to comprise that the patient has not previously been treated with the complement inhibitor eculizumab as taught by Bedrosian. This is obvious because, the combined teachings of ‘377, ‘574, and Bedrosian teach a method of treating a human patient with refractory generalized MG comprising administering ravulizumab comprising a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:11 to the patient, wherein a treatment effect is observed at week 1 after initiation of treatment, and Bedrosian teaches that subjects who have received previous treatment with eculizumab, a terminal complement inhibitor, are part of the subject exclusion criteria. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method for treating a human patient with MG, the method comprising administering ravulizumab to the patient, wherein:
ravulizumab comprises CDRH1-H3 comprising the amino acid sequences SEQ ID NOs:19, 18, and 3, respectively, and CDRL1-L3 comprising the amino acid sequences SEQ ID NOs:4-6, respectively;
the instant treatment effect is observed at week 1 after initiation of treatment; and
the patient has not previously been treated with a complement inhibitor wherein the complement inhibitor comprises eculizumab.
Claims 1-3, 5-6, 8-9, 13-20, and 43-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, and 14-15 of U.S. Patent No. 12,459,992B2 (Bedrosian et al, Priority to May 27, 2016, hereinafter ‘992). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1-3, 13, and 20, claim 1 of ‘992 is directed to a method of treating refractory generalized myasthenia gravis in a patient in need thereof comprising administering a therapeutically effective amount of an eculizumab variant comprising a heavy chain amino acid sequence according to SEQ ID NO:14 and a light chain amino acid sequence according to SEQ ID NO:11 to the patient, wherein the patient is positive for auto-antibodies binding to nicotinic acetylcholine receptor (anti-AChR) and the patient is administered the eculizumab variant for at least 26 weeks. SEQ ID NO:14 and SEQ ID NO:11 comprise the heavy chain and light chain, respectively, of the eculizumab variant BNJ441, also known as ALXN1210 or ravulizumab (see claim 14 of ‘992 and Example 4 of ‘992 specification starting on page 88, specifically page 89, second paragraph). Furthermore, the instant specification discloses that the administration cycle of the instant treatment is 26 weeks (page 26, lines 22-23). Claim 6 of ‘992 recites that the eculizumab variant is administered intravenously.
Regarding instant claims 14-19, claim 2 of ‘992 is directed to the method of claim 1 of ‘992, wherein the eculizumab variant (e.g. ravulizumab) is administered at a dose between 600 mg and 6000 mg and wherein the patient is administered the eculizumab variant for at least 26 weeks.
Regarding instant claims 5-6 and 8-9, claims 3 and 4 of ‘992 are directed to the method of claim 1 of ‘992, wherein the patient experiences a clinically meaningful improvement (reduction) in MG-ADL score or in quantitative Myasthenia Gravis score (QMG) after 26 weeks of treatment, wherein the clinically meaningful improvement the patient experiences is at least a 3 point reduction in the patient's MG-ADL score or at least a 4 point reduction in the patient's QMG score after 26 weeks of treatment. Claim 15 of ‘992 recite that the eculizumab variant is ravulizumab.
Claim 5 of ‘992 recite a method of treating refractory generalized myasthenia gravis in a patient in need thereof comprising administering an eculizumab variant comprising a heavy chain amino acid sequence according to SEQ ID NO:14 and a light chain amino acid sequence according to SEQ ID NO:11 to the patient (see discussion above for instant claims 1-2 and 13), wherein:
the patient is positive for auto-antibodies binding to anti-AChR (see discussion above for instant claim 3);
the eculizumab variant is administered at a dose between 600 mg and 6000 mg, wherein the patient is administered the eculizumab variant for at least 26 weeks (see discussion above for instant claims 14-19); and
wherein the patient has a clinically meaningful improvement (reduction) in at least two measurements of generalized myasthenia gravis severity selected from the group consisting of MG-ADL, QMG, MGC, MG-QOL, and Neuro-QOL (see instant claims 43-46 and the discussion above for instant claims 5-6 and 8-9).
Therefore, although the claims at issue are not identical, the instant claims are not patentably distinct from the issue claims.
Claims 1-3, 5-6, 8-9, 13-21, and 43-46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 43, 57, 59-60, 62, 64, 71, and 73-76 of copending Application No. 18/933,215 (US20250243264A1, Priority to February 14, 2019; hereinafter ‘215). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claims 1, 3, 14, 16, 18, and 20, claim 43 of ‘215 is directed to a method of treating a human patient with myasthenia gravis (MG), the method comprising administering to the patient an effective amount of an antibody or an antigen binding fragment thereof comprising a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:11 (SEQ ID NO:14 and SEQ ID NO:11 are identical to instant SEQ ID Nos 14 and 11, respectively, comprising the CDRs recited in instant claim 1), wherein the antibody or the antigen binding fragment thereof is to be administered to the patient in:
an administration cycle comprising administering: once on Day 1 at a loading dose of:
2400 mg to a patient weighing ≥40 to <60 kg (see instant claim 14),
2700 mg to a patient weighing ≥60 to <100 kg (see instant claim 16), or
3000 mg to a patient weighing ≥100 kg (see instant claim 18); and
on Day 15 and every eight weeks thereafter at a maintenance dose of:
3000 mg to a patient weighing ≥40 to <60 kg (see instant claim 14),
3300 mg to a patient weighing ≥60 to <100 kg (see instant claim 16), or
3600 mg to a patient weighing ≥100 kg (see instant claim 18);
wherein the antibody or the antigen binding fragment thereof is formulated for intravenous administration (see instant claim 20), and wherein the patient is anti-AChR antibody positive (see instant claim 3).
Regarding instant claim 2, claim 73 of ‘215 recites he method according to claim 43 of ‘215 discussed above, wherein the antibody is ravulizumab.
Regarding instant claims 5-6, claim 62 of ‘215 is directed to the method according to claim 43 of ‘215 discussed above, wherein the treatment results in the patient experiencing a clinically meaningful improvement (reduction) in a MG-ADL score after 26 weeks of treatment, wherein the clinically meaningful improvement the patient experiences is at least a 3 point reduction in the patient's MG-ADL score after 26 weeks of treatment.
Regarding instant claims 8-9, claim 64 of ‘215 is directed to the method according to claim 43 of ‘215 discussed above, wherein the treatment results in a clinically meaningful improvement (reduction) in QMG after 26 weeks of treatment, wherein the clinically meaningful improvement the patient experiences is at least a 5 point reduction in the patient's QMG after 26 weeks of treatment.
Regarding instant claim 13, claim 71 of ‘215 recites that the method according to claim 43 of ‘215 discussed above, wherein the myasthenia gravis is generalized myasthenia gravis
Regarding instant claims 15, 17, and 19, claim 57 of ‘215 recites the method according to claim 43 of ‘215 discussed above, wherein the antibody or the antigen binding fragment thereof is administered at a dose of 3000 mg (see instant claim 15), 3300 mg (see instant claim 17) or 3600 mg (see instant claim 19) every eight weeks after the administration cycle for up to two years.
Regarding instant claim 21, claim 59 of ‘215 recites that the method according to claim 43 of ‘215 discussed above, wherein the patient has not previously been treated with a complement inhibitor.
Regarding instant claims 43-44, see the discussions for claims 43 and 62 of ‘215 above.
Regarding instant claims 45-46, see the discussions for claims 43 and 64 of ‘215 above.
Claim 60 of ‘215 recites that the administration cycle for the treatment described in claim 43 of ‘215 is a total of 26 weeks of treatment. As discussed above, the instant specification discloses that the administration cycle of the instant treatment is 26 weeks (page 26, lines 22-23).
Claims 75 and 76 of ‘215 are directed to a kit comprising the antibody ravulizumab. Absent a limiting definition for a “kit”, the broadest reasonable interpretation is any container comprising the instant antibody or antibody binding fragment thereof. Furthermore, Printed instructions do not distinguish the claimed product (MPEP 2112.01 (III)).
Therefore, although the claims at issue are not identical, they are not patentably distinct from each other.
Conclusion
No claims are allowed.
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/J.H./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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