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 .
DETAILED ACTION
Status of the Claims
1. Claims 1-6 are the original claims filed 3/30/2023. Claims 1-6 are all the claims.
Priority
2. USAN 18/029,525, filed 03/30/2023, is a National Stage entry of PCT/US2021/053540, International Filing Date: 10/05/2021, PCT/US2021/ 053540, Claims Priority from Provisional Application 63/087,577, filed 10/05/2020.
The priority date for Provisional Application 63/087,577, filed 10/05/2020, is granted. Claims 1-6 are identical to claims 1-6 of ‘577 and a method of treating dermatomyositis of claims 1, 2 and 6 is supported in Example 1 of the specification.
Information Disclosure Statement
3. As of 12/10/2025, no IDS is of record for this application.
Objections
Specification
4. The abstract of the disclosure is objected to because it contains exemplary language “e.g.,”. The POSA cannot reasonably ascertain if the text is intended subject matter of the invention. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
5. The disclosure is objected to because of the following informalities:
a) The use of the term, Tris, POROS, Triton, Expi293, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
6. Claim 4 is objected to because of the following informalities:
a) Amend claim 4 to recite “multi-chambered, pre-filled syringe.”
b) Amend claim 4 to recite “lyophilized [lyo] syringe.”
Appropriate correction is required.
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.
7. Claim(s) 1-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Puffer et al (WO 2019014360; published 1/17/2019; priority to 11/7/2017) in view of Clinicaltrials.gov NCT00005571 (“safety and effectiveness of h5G1.1 mab for dermatomyositis”; posted 4/6/2000) and Abbvie (US 20160082189).
1. A method of treating a subject having or suspected of having dermatomyositis, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a fusion protein having the sequence of SEQ ID NO:1 and a pharmaceutically acceptable carrier.
Puffer discloses a method of treating a subject having or suspected of having a complement-mediated disorder (a method of treating a subject having or suspected of having a complement-mediated disorder (pg.7,lines.25-27), comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a fusion protein having the sequence of SEQ ID NO:1 (comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a fusion protein having the sequence of SEQ ID NO: 96, wherein SEQ ID NO:96 of Puffer comprises 100% sequence identity to instant SEQ ID NO:1; pg.3,Iins.1-2; pg.7,Ins.25-27) and a pharmaceutically acceptable carrier (and a pharmaceutically acceptable carrier; pg.3, Ins.16-18).
SEQ ID NO: 1 comprises an anti-HSA (VHH) x anti-C5 (VHH) fusion protein as the same of ref SEQ ID NO: 96:
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NCT00005571 teaches the field of treatment of dermatomyositis (Title; pg.2, first para.) and teaches a method of treating a subject having or suspected of having dermatomyositis comprising administering an antibody specific for complement component C5 (a method of treating a subject having or suspected of having dermatomyositis comprising administering an antibody specific for complement component C5; pg.2, first para.; pg.2, last para.).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Puffer with the teaching of NCT ‘571 for the purpose of extending the use of a C5 targeted antibody with improved pharmaceutical properties (Puffer pg.1, Ins. 20-25) to include additional medical conditions where an antibody to C5 has been found or considered as a viable treatment for dermatomyositis.
2. A medical device for treating a subject having or suspected of having dermatomyositis, the medical device comprising a pharmaceutical composition comprising the fusion protein of SEQ ID NO:1 and a pharmaceutically acceptable carrier.
Puffer discloses a medical device (a pre-filled syringe; pg. 40, Ins.1-6) for treating a subject having or suspected of having a complement-mediated disorder (treating a subject having or suspected of having a complement-mediated disorder, pg.7, Ins.25-27), the medical device comprising a pharmaceutical composition (the syringe comprising a pharmaceutical composition; pg.3, Ins.16-18; pg.40,I ns.1-6) comprising the fusion protein of SEQ ID NO:1 (comprising the fusion protein of SEQ ID NO:96, wherein SEQ ID NO:96 of Puffer comprises 100% sequence identity to instant SEQ ID NO:1; pg.3, Ins.:1 -2;pg.7, Ins.25-27) and a pharmaceutically acceptable carrier (and a pharmaceutically acceptable carrier; pg.3,Ins.16-18).
NCT ‘571 is in the field of treatment of dermatomyositis (Title; pg.2,first para.) and teaches a method of treating a subject having or suspected of having dermatomyositis comprising administering an antibody specific for complement component C5 (a method of treating a subject having or suspected of having dermatomyositis comprising administering an antibody specific for complement component C5; pg.2, first para.; pg.2, last para.).It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Puffer with the teaching of NCT ‘571 for the purpose of extending the use of a C5 targeted antibody with improved pharmaceutical properties (Puffer, pg.1, Ins. 20-25) to include additional medical conditions where an antibody to C5 has been found or considered as a viable treatment.
3. The medical device of claim 2, wherein the device is an autoinjector or a pre-filled syringe.
Puffer discloses the medical device of claim 2, where in the device is an auto injector or a pre-filled syringe (a pre-filled syringe; pg. 40, Ins.1-6).
4. The medical device of claim 3, wherein the pre-filled syringe is a multi-chambered pre-filled syringe or a lyo syringe.
Puffer discloses the medical device of claim 3, wherein the pre-filled syringe is a multi-chambered pre-filled syringe or a lyo syringe (a multi-chambered pre-filled syringe; pg.40, Ins.1-6).
5. The medical device of claim 2, wherein the device is a wearable device.
Puffer discloses the medical device of claim 2. Abbvie is in the field of wearable automatic injection devices (wearable automatic injection devices; abstract), and teaches wear able automatic injection devices for subcutaneous delivery of agents, including antibodies (wear able automatic injection devices for subcutaneous delivery of agents, including antibodies; para. [0004)). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Puffer with the teaching of Abbvie for the purpose of providing to a subject a device capable of delivering the antibody disclosed by Puffer on a continuous or scheduled basis to better enable control of the dosing of the antibody over time to produce a therapeutic effect in the subject (Abbvie, para.[0004)).
6. A therapeutic kit comprising: (a) a container comprising a label; and (b) a composition comprising the fusion protein of SEQ ID NO:1 and a pharmaceutically acceptable carrier; wherein the label indicates that the composition is to be administered to a subject having, or who is suspected of having dermatomyositis.
Puffer discloses a therapeutic kit comprising: (a) a container comprising a label (a therapeutic kit comprising: (a) a container comprising a label; pg. 7, Ins.19-22); and (b) a composition comprising the fusion protein of SEQ ID NO:1 and a pharmaceutically acceptable carrier (a composition comprising the fusion protein of SEQ ID NO: 96 and a pharmaceutically acceptable carrier: pg. 3, Ins.1-2, Ins.16-18; pg. 7,Ins. 25-27); wherein the label indicates that the composition is to be administered to a subject having, or who is suspected of having a complement-mediated disorder (wherein the label indicates that the composition is to be administered to a subject having, or who is suspected of having a complement-mediated disorder; pg.7, Ins.19-22).
NCT ‘571 is in the field of treatment of dermatomyositis (Title; pg.2, first para.) and teaches a method of treating a subject having or suspected of having dermatomyositis comprising administering an antibody specific for complement component C5 (a method of treating a subject having or suspected of having dermatomyositis comprising administering an antibody specific for complement component C5; pg.2, first para.; pg.2, last para.). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Puffer with the teaching of NCT ‘571 for the purpose of extending the use of a C5 targeted antibody with improved pharmaceutical properties (Puffer, pg.1, Ins. 20-25) to include additional medical conditions where an antibody to C5 has been found or considered as a viable treatment.
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.
8. Claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11498960. The reference patent is not afforded safe harbor under 35 USC 121 because the ref claims share no continuity nor a restriction/ speciation with the claims for the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ref claimed anti-C5 VHH-linker-anti HSA VHH fusion protein of ref SEQ ID NO: 96 is 100% identical to the instant sequence of SEQ ID NO: 1:
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The POSA could reasonably conclude the VHH CDR1-3 for the C5 domain and HSA domain shown in ref claim 1 correspond to the CDRs in the sequence of SEQ ID NO: 96 shown.
1. A fusion protein comprising an engineered polypeptide comprising a VHH domain that specifically binds to human complement component C5 and an engineered polypeptide comprising a VHH domain that specifically binds to human serum albumin, wherein the engineered polypeptide comprising the VHH domain that specifically binds to human complement component C5 is fused to the engineered polypeptide comprising the VHH domain that specifically binds to human serum albumin either directly or via a peptide linker; wherein the VHH domain that specifically binds to human complement component C5 comprises three complementarity determining regions, CDR1, CDR2 and, CDR3, wherein CDR1 comprises the amino acid sequence of SEQ ID NO:16, CDR2 comprises the amino acid sequence of SEQ ID NO:18, and CDR3 comprises the amino acid sequence of SEQ ID NO:20; and wherein the VHH domain that specifically binds to human serum albumin comprises three complementarity determining regions, CDR1, CDR2, and CDR3, wherein CDR1 comprises the amino acid sequence of SEQ ID NO:38, CDR2 comprises the amino acid sequence of SEQ ID NO:48, and CDR3 comprises the amino acid sequence of SEQ ID NO:55.
2. The fusion protein of claim 1, wherein the C-terminal residue of the polypeptide that specifically binds to human serum albumin is fused either directly or via a linker to the N-terminal residue of the polypeptide that specifically binds to human complement component C5.
3. The fusion protein of claim 1, wherein the C-terminal residue of the polypeptide that specifically binds to human complement component C5 is fused either directly or via a linker to the N-terminal residue of the polypeptide that specifically binds to human serum albumin.
The POSA could reasonably conclude the VHH for the C5 domain and the VHH for the HSA domain shown in ref claim 4 correspond to the VHH domains in the sequence of SEQ ID NO: 96.
4. A fusion protein comprising an engineered polypeptide comprising a VHH domain that specifically binds to human complement component C5 and an engineered polypeptide comprising a VHH domain that specifically binds to human serum albumin, wherein the engineered polypeptide comprising the VHH domain that specifically binds to human complement component C5 is fused to the engineered polypeptide comprising the VHH domain that specifically binds to human serum albumin either directly or via a peptide linker, wherein the polypeptide that specifically binds to human complement component C5 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:1-12 and fragments thereof; and the polypeptide that specifically binds to human serum albumin comprises an amino acid selected from the group consisting of SEQ ID NOs:22-34 and fragments thereof.
5. The fusion protein of claim 4, wherein the polypeptide that specifically binds to human complement component C5 comprises the amino acid sequence of SEQ ID NO:11 and the polypeptide that specifically binds to human serum albumin comprises the amino acid sequence of SEQ ID NO:26.
6. The fusion protein of claim 5, further comprising a peptide linker having an amino acid sequence of SEQ ID NO:102 or 103.
7. The fusion protein of claim 6, wherein the peptide linker comprises the amino acid sequence of SEQ ID NO:102.
The POSA could reasonably conclude the sequence of SEQ ID NO: 1 is identical to the sequence of SEQ ID NO: 96.
8. The fusion protein of claim 1, wherein the fusion protein comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:96.
9. The fusion protein of claim 8, wherein the fusion protein consists of the sequence of SEQ ID NO:96.
10. The fusion protein of claim 1, wherein either or both of the polypeptides that bind to human complement component C5 or albumin bind in a pH-dependent manner.
11. A pharmaceutical composition comprising a therapeutically effective amount of a fusion protein of claim 1 and a pharmaceutically acceptable carrier.
12. The pharmaceutical composition of claim 11, further comprising hyaluronidase.
13. An engineered polypeptide comprising a VHH domain that binds to human complement component C5, wherein the engineered polypeptide comprises an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO:11; wherein the VHH domain that specifically binds to human complement component C5 comprises three complementarity determining regions, CDR1, CDR2 and, CDR3, wherein CDR1 comprises the amino acid sequence of SEQ ID NO:16, CDR2 comprises the amino acid sequence of SEQ ID NO:18, and CDR3 comprises the amino acid sequence of SEQ ID NO:20.
14. An engineered polypeptide comprising a VHH domain that binds to human complement component C5, wherein the engineered polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:1-12 and fragments thereof.
9. Claims 1-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-46 of copending Application No. 19/007,782 (reference application 20250163138).
The reference is not afforded safe harbor under 35 USC 121 because the ref claims share no continuity nor a restriction/ speciation with the claims for the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ref claimed anti-C5 VHH-linker-anti HSA VHH fusion protein of ref SEQ ID NO: 96 is 100% identical to the instant sequence of SEQ ID NO: 1:
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The POSA could reasonably conclude the VHH CDR1-3 for the C5 domain and HSA domain shown in ref claim 1 correspond to the CDRs in the sequence of SEQ ID NO: 96 shown.
30. (Currently Amended) A method for treating a patient having a complement-mediated disorder, the method comprising administering to the patient a therapeutically effective amount of a fusion protein of any one of Claims 1-13 comprising an engineered polypeptide comprising a VHH domain that specifically binds to human complement component C5 and an engineered polypeptide comprising a VHH domain that specifically binds to human serum albumin, wherein the engineered polypeptide comprising the VHH domain that specifically binds to human complement component C5 is fused to the engineered polypeptide comprising the VHH domain that specifically binds to human serum albumin either directly or via a peptide linker; wherein the VHH domain that specifically binds to human complement component C5 comprises three complementarity determining regions, CDR1,CDR2 and, CDR3, wherein CDR1 comprises the amino acid sequence of SEQ ID NO:16, CDR2 comprises the amino acid sequence of SEQ ID NO:18, and CDR3 comprises the amino acid sequence of SEQ ID NO:20; and wherein the VHH domain that specifically binds to human serum albumin comprises three complementarity determining regions, CDR1, CDR2, and CDR3, wherein CDR1 comprises the amino acid sequence of SEQ ID NO:38, CDR2 comprises the amino acid sequence of SEQ ID NO:48, and CDR3 comprises the amino acid sequence of SEQ ID NO:55.
31. (Original) The method of Claim 30, wherein the complement-mediated disorder is selected from the group consisting of: rheumatoid arthritis; lupus nephritis; asthma; ischemia-reperfusion injury;atypical hemolytic uremic syndrome; dense deposit disease; paroxysmal nocturnal hemoglobinuria;macular degeneration; hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome;Guillain-Barr6 Syndrome; CHAPLE syndrome; myasthenia gravis; neuromyelitis optica;post-hematopoietic stem cell transplant thrombotic microangiopathy (post-HSCT-TMA); post-bone marrow transplant TMA (post-BMT TMA); Degos disease; Gaucher's disease; glomerulonephritis;thrombotic thrombocytopenic purpura (TTP); spontaneous fetal loss; Pauci-immune vasculitis;epidermolysis bullosa; recurrent fetal loss; multiple sclerosis (MS); traumatic brain injury; and injury resulting from myocardial infarction, cardiopulmonary bypass and hemodialysis.
32. (New) The method of Claim 30, wherein the C-terminal residue of the engineered polypeptide that specifically binds to human serum albumin is fused either directly or via a linker to the N-terminal residue of the engineered polypeptide that specifically binds to human complement component C5.
33. (New) The method of Claim 30, wherein the C-terminal residue of the engineered polypeptide that specifically binds to human complement component C5 is fused either directly or via a linker to the N-terminal residue of the engineered polypeptide that specifically binds to human serum albumin.
34. (New) The method of Claim 30, wherein the engineered polypeptide that specifically binds to human complement component C5 comprises the amino acid sequence of SEQ ID NO:11 and the engineered polypeptide that specifically binds to human serum albumin comprises the amino acid sequence of SEQ ID NO:26.
35. (New) The method of Claim 30, wherein the fusion protein further comprises a peptide linker having an amino acid sequence of SEQ ID NO:102 or 103.
36. (New) The method of Claim 35, wherein the peptide linker comprises the amino acid sequence of SEQ ID NO:102.
37. (New) The method of Claim 30, wherein the fusion protein comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:96.
38. (New) The method of Claim 37, wherein the fusion protein consists of the sequence of SEQ ID NO:96.
39. (New) The method of Claim 30, wherein either or both of the engineered polypeptides that bind to human complement component C5 or albumin bind in a pH-dependent manner.
40. (New) The method of claim 30, wherein a pharmaceutical composition comprising a therapeutically effective amount of the fusion protein and a pharmaceutically acceptable carrier are administered.
41. (New) A method for treating a patient having a complement-mediated disorder, the method comprising administering to the patient a therapeutically effective amount of a fusion protein comprising an engineered polypeptide comprising a VHH domain that specifically binds to human complement component C5 and an engineered polypeptide comprising a VHH domain that specifically binds to human serum albumin, wherein the engineered polypeptide comprising the VHH domain that specifically binds to human complement component C5 is fused to the engineered polypeptide comprising the VHH domain that specifically binds to human serum albumin either directly or via a peptide linker, wherein the polypeptide that specifically binds to human complement component C5 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:1-12 and fragments thereof; and the polypeptide that specifically binds to human serum albumin comprises an amino acid selected from the group consisting of SEQ ID NOs:22-34 and fragments thereof.
42. (New) The method of Claim 41, wherein the complement-mediated disorder is selected from the group consisting of: rheumatoid arthritis; lupus nephritis; asthma; ischemia-reperfusion injury;atypical hemolytic uremic syndrome; dense deposit disease; paroxysmal nocturnal hemoglobinuria;macular degeneration; hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome;Guillain-Barr6 Syndrome; CHAPLE syndrome; myasthenia gravis; neuromyelitis optica;post-hematopoietic stem cell transplant thrombotic microangiopathy (post-HSCT-TMA); post-bone marrow transplant TMA (post-BMT TMA); Degos disease; Gaucher's disease; glomerulonephritis;thrombotic thrombocytopenic purpura (TTP); spontaneous fetal loss; Pauci-immune vasculitis;epidermolysis bullosa; recurrent fetal loss; multiple sclerosis (MS); traumatic brain injury; and injury resulting from myocardial infarction, cardiopulmonary bypass and hemodialysis.
43. (New) The method of Claim 41, wherein the C-terminal residue of the engineered polypeptide that specifically binds to human serum albumin is fused either directly or via a linker to the N-terminal residue of the engineered polypeptide that specifically binds to human complement component C5.
44. (New) The method of Claim 41, wherein the C-terminal residue of the engineered polypeptide that specifically binds to human complement component C5 is fused either directly or via a linker to the N-terminal residue of the engineered polypeptide that specifically binds to human serum albumin.
45. (New) The method of Claim 41, wherein either or both of the engineered polypeptides that bind to human complement component C5 or albumin bind in a pH-dependent manner.
46. (New) The method of claim 41, wherein a pharmaceutical composition comprising a therapeutically effective amount of the fusion protein and a pharmaceutically acceptable carrier are administered.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
10. Claims 1-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-60 of copending Application No. 18/871,129 (reference application).
The reference is not afforded safe harbor under 35 USC 121 because the ref claims share no continuity nor a restriction/ speciation with the claims for the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ref claimed anti-C5 VHH-linker-anti HSA VHH fusion protein of ref SEQ ID NO: 9 is 100% identical to the instant sequence of SEQ ID NO: 1:
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The POSA could reasonably conclude the VHH CDR1-3 for the C5 domain and HSA domain shown in ref claim 1 correspond to the CDRs in the sequence of SEQ ID NO: 9 shown.
1. A method of treating myasthenia gravis (MG) in a human subject in need thereof, comprising administering to the human subject a therapeutically effective dose of a fusion protein comprising an engineered polypeptide that specifically binds human complement component C5 fused to an engineered polypeptide that specifically binds to human serum albumin, wherein the engineered polypeptide that specifically binds to human complement component C5 is fused to the engineered polypeptide that specifically binds to human serum albumin via a peptide linker, wherein the engineered polypeptide that specifically binds to human complement component C5 comprises three complementarity determining regions, CDR1, CDR2 and CDR3, comprising amino acid sequences as set forth in SEQ ID NOs: 5, 6 and 7, respectively, and wherein the engineered polypeptide that specifically binds to human serum albumin comprises three complementarity determining regions, CDR1, CDR2 and CDR3, comprising amino acid sequences as set forth in SEQ ID NOs: 1, 2 and 3, respectively.
2. The method of claim 1, wherein the polypeptide that specifically binds to human serum albumin comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 4.
3. The method of claim 2, wherein the polypeptide that specifically binds to human serum albumin comprises an amino acid sequence of SEQ ID NO: 4.
4. The method of any one of claims 1-3, wherein the polypeptide that specifically binds to human complement component C5 comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 8.
5. The method of claim 4, wherein the polypeptide that specifically binds to human complement component C5 comprises an amino acid sequence of SEQ ID NO: 8.
6. The method of any one of claims 1-5, wherein the peptide linker comprises the amino acid sequence of SEQ ID NO:10.7 The method of any one of claims 1-6, wherein the fusion protein comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 9.
8. The method of claim 7, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO: 9.
9. The method of any one of claims 1-8, wherein the subject is positive for auto-antibodies binding to nicotinic acetylcholine receptor (anti-AChR)
10. The method of any one of claims 1-9, wherein the MG is generalized myasthenia gravis (gMG).
11. The method of any one of claims 1-10, wherein the subject has been diagnosed with MG for at least 3 months.
12. The method of any one of claims 1-11, wherein the subject is 18 years old or older in age.
13. The method of any one of claims 1-12, wherein the subject has a Myasthenia Gravis Foundation of America (MGFA) clinical classification of between II and IV.
14. The method of any one of claims 1-13, wherein the patient has a Myasthenia Gravis Activities of Daily Living (MG-ADL) score greater than or equal to 5.
15. The method of any one of claims 1-14, wherein the subject is being administered one or more additional pharmaceutical compositions.
16. The method of claim 15, wherein the pharmaceutical composition is an acetylcholinesterase inhibitor, an immunosuppressive therapy (IST), or immunoglobulins.
17. The method of claim 16, wherein IST is selected from the group consisting of a corticosteroid, azathioprine (AZA), mycophenolate mofetil (MMF), methotrexate (MTX), cyclosporine, cyclophosphamide, and tacrolimus (TAC).
18. The method of any one of claims 1-17, wherein the subject has not been administered a B cell-depleting therapy in the prior 6 months.
19. The method of claim 18, wherein the B cell-depleting therapy is rituximab or ocrelizumab.
20. The method of any one of claims 1-19, wherein the subject has not been administered an FcRn inhibitor within 5 half-lives of the FcRn before administration of the fusion protein.
21. The method of any one of claims 1-20, wherein the subject has not been administered a complement inhibitor within 5 half-lives of the complement inhibitor before administration of the fusion protein.
22. The method of any one of claims 1-21, wherein the subject weighs at least 40 kg.
23. The method of any one of claims 1-22, wherein the subject has a body mass index of > 18.5 kg/m2 and < 40 kg/m2.
24. The method of any one of claims 1-23, wherein the therapeutically effective dose is based on the weight of the subject.
25. The method of any one of claims 1-24 wherein the fusion protein is administered to a patient weighing < 80 kg:(a) once on Day 1 of the administration cycle at a loading dose of 600 mg; and(b) on Day 8 of the administration cycle and every week thereafter at a maintenance dose of 300 mg.
26. The method of claim 25, wherein fusion protein is administered at a dose of 300 mg every week after the administration cycle for up to two years.
27. The method of any one of claims 1-24, wherein the fusion protein is administered to a patient weighing > 80 kg:(a) once on Day 1 of the administration cycle at a loading dose of 900 mg; and(b) on Day 8 of the administration cycle and every week thereafter at a maintenance dose of 600 mg.
28. The method of claim 27, wherein fusion protein is administered at a dose of 600 mg every week after the administration cycle for up to two years
29. The method of any one of claims 1-28, wherein the fusion protein is administered to the subject subcutaneously.
30. The method of any one of claims 1-29, wherein the fusion protein is administered to the subject using a pre-filled syringe.
31. The method of claim 30, wherein the pre-filled syringe comprises a passive needle safety device.
32. The method of any one of claims 1-31, wherein the treatment results in the patient experiencing a change from baseline in MG-ADL score.
33. The method of any one of claims 1-32 wherein the treatment results in the patient experiencing a change from baseline in MG-ADL score after 26 weeks.
34. The method of any one of claims 1-33, wherein the treatment results in the patient experiencing a reduction in the MG-ADL score after 26 weeks.
35. The method of claim 34, wherein the reduction is at least 3.0 points.
36. The method of claim 34, wherein the reduction is at least 4.0 points.
37. The method of any one of claims 1-36, wherein the treatment results in the patient experiencing a change from baseline in quantitative Myasthenia Gravis (QMG) score.
38. The method of any one of claims 1-37, wherein the treatment results in the patient experiencing a change from baseline in QMG score after 26 weeks.
39. The method of any one of claims 1-38, wherein the treatment results in the patient experiencing a reduction in QMG score after 26 weeks.
40. The method of claim 39, wherein the reduction is at least 2.0 points.
41. The method of claim 39, wherein the reduction is at least 5.0 points.
42. The method of any one of claims 1-41, wherein the treatment results in the patient experiencing a change from baseline in quantitative Myasthenia Gravis composite (MGC) score.
43. The method of any one of claims 1-42, wherein the treatment results in the patient experiencing a change from baseline in MGC score after 26 weeks.
44. The method of any one of claims 1-43, wherein the treatment results in the patient experiencing a reduction in MGC score after 26 weeks.
45. The method of any one of claims 1-44, wherein the treatment results in subject experiencing a change from baseline in serum free or total C5 concentration.
46. The method of any one of claims 1-45, wherein the treatment results in the patient experiencing a change from baseline in MG Quality of Life 15 (MG-QoL15r) score after 26 weeks.
47. The method of any one of claims 1-46, wherein the treatment results in the patient experiencing a change from baseline in EQ-5D-5L score after 26 weeks.
48. The method of any one of claims 1-47, wherein the treatment results in the patient experiencing a change from baseline in SF-36 score after 26 weeks.
49. The method of any one of claims 1-48, wherein the treatment results in the patient experiencing a change from baseline in Neuro-QoL Fatigue (Quality of Life in Neurological Disorders Fatigue Short Form)) score after 26 weeks.
50. The method of any one of claims 1-49, wherein the treatment results in the patient experiencing an MG-ADL score of 1 or less after 26 weeks.
51. The method of any one of claims 1-50, wherein the treatment results in the patient experiencing a change in MGFA postintervention status after 26 weeks.
52. The method of any one of claims 1-51, wherein the treatment results in the patient experiencing a reduction in incidence of clinical deteriorations after 26 weeks.
53. The method of any one of claims 1-52, wherein the treatment results in the patient experiencing a reduction in incidence of hospitalizations after 26 weeks.
54. The method of any one of claims 1-53, wherein the treatment results in the patient experiencing a reduction in incidence of requiring rescue therapy after 26 weeks.
55. The method of any one of claims 1-54, wherein the treatment results in a change in concentration of one or more inflammation biomarkers.
56. The method of claim 55, wherein the one or more inflammation biomarkers comprises MMP- 10 or IL-6.
57. The method of any one of claims 1-56, wherein the treatment results in a change in concentration of complement proteins or complement pathway regulators.
58. The method of any one of claims 1-57, wherein the treatment effect is maintained through week 26 after initiation of treatment.
59. The method of any one of claims 1-58, wherein the treatment effect is maintained through week 96 after initiation of treatment.
60. A method of treating gMG in a human subject in need thereof, comprising administering to the human subject a therapeutically effective dose of a fusion protein comprising an engineered polypeptide that specifically binds human complement component C5 fused to an engineered polypeptide that specifically binds to human serum albumin, wherein the engineered polypeptide that specifically binds to human complement component C5 is fused to the engineered polypeptide thatspecifically binds to human serum albumin via a peptide linker, wherein the engineered polypeptide that specifically binds to human complement component C5 comprises three complementarity determining regions, CDR1, CDR2 and CDR3, comprising amino acid sequences as set forth in SEQ ID NOs: 5, 6 and 7, respectively, and wherein the engineered polypeptide that specifically binds to human serum albumin comprises three complementarity determining regions, CDR1, CDR2 and CDR3, comprising amino acid sequences as set forth in SEQ ID NOs: 1, 2 and 3, respectively, wherein the subject is positive for auto-antibodies binding to nicotinic acetylcholine receptor (anti-AChR);wherein the subject is 18 years old or older in age,(a) wherein the fusion protein is administered to a patient weighing < 80 kg:(i) once on Day 1 of the administration cycle at a loading dose of 600 mg; and(ii) on Day 8 of the administration cycle and every week thereafter at a maintenance dose of 300 mg, and wherein fusion protein is administered at a dose of 300 mg every week after the administration cycle for up to two years, or (b) wherein the fusion protein is administered to a patient weighing >: 80 kg:(i) once on Day 1 of the administration cycle at a loading dose of 900 mg; and(ii) on Day 8 of the administration cycle and every week thereafter at a maintenance dose of 600 mg, and wherein fusion protein is administered at a dose of 600 mg every week after the administration cycle for up to two years, andwherein the subject has an improvement from baseline in at least one measurement of gMG severity selected from the group consisting of MG-ADL, QMG, MGC, MG-QoL15r, EQ-5D-5L, SF-36 and Neuro-QoL Fatigue.
This is a provisional rejection.
11. Claims 1-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5(vii), 10, 15-18, 20, 31-32, 34-37, and 44-45 of copending Application No. 18/682,310 (reference application 20240343786).
The reference is not afforded safe harbor under 35 USC 121 because the ref claims share no continuity nor a restriction/ speciation with the claims for the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ref claimed anti-C5 VHH-linker-anti HSA VHH fusion protein of ref SEQ ID NO: 46 is 100% identical to the instant sequence of SEQ ID NO: 1:
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1. (Currently Amended) A method for treating sickle cell disease (SCD), 13-thalassemia (BT), or sickle cell BT in a subject, comprising administering to the subject an effective amount of a composition comprising a complement C5 inhibitor.
2. - 3. (Cancelled)
4. (Currently Amended) The method of any one of The method of any one of wherein (a) the complement C5 inhibitor is selected from the group consisting of an antibody or an antigen-binding fragment thereof, a peptide, a small molecule, a nucleic acid molecule, and an aptameri(b)the composition comprises the complement C5 inhibitor and a pharmaceutically acceptable carrier;(c)the method reduces intravascular hemolysis in the subject;(d)the subject is a human patient diagnosed as having SCD, BT, or sickle cell BT;(e) upon administration of the complement C5 inhibitor to the subject, the subject exhibits a reduction in a SCD, BT, or sickle cell BT phenotype; and/or (f)the composition is administered intravenously.
5. (Currently Amended) The method of Claim 4, wherein;(a) the complement C5 inhibitor is an anti-C5 antibody or antigen-binding fragment thereof, wherein the anti-C5 antibody or antigen-binding fragment thereof comprises:(i)the complementarity determining region-heavy chain 1 (CDR-H1) of SEQ ID NO: 5,the CDR-H2 of SEQ ID NO: 6, and the CDR-H3 of SEQ ID NO: 7;(ii) the CDR-H1 of SEQ ID NO: 8, the CDR-H2 of SEQ ID NO: 9, the CDR-H3 of SEQ ID NO: 10, the complementarity determining region-light chain 1 (CDR-L1) of SEQ ID NO: 11, the CDR-L2 of SEQ ID NO: 12, and the CDR-L3 of SEQ ID NO: 13;(iii) the CDR-H1 of SEQ ID NO: 14, the CDR-H2 of SEQ ID NO: 15, the CDR-H3 of SEQ ID NO: 16, the CDR-L1 of SEQ ID NO: 17, the CDR-L2 of SEQ ID NO: 18, and the CDR-L3 of SEQ ID NO: 19;(iv)the CDR-H1 of SEQ ID NO: 20, the CDR-H2 of SEQ ID NO: 21, the CDR-H3 of SEQ ID NO: 22, the CDR-L1 of SEQ ID NO: 23, the CDR-L2 of SEQ ID NO: 24, and the CDR-L3 of SEQ ID NO: 25;(v)the CDR-H1 of SEQ ID NO: 26, the CDR-H2 of SEQ ID NO: 27, the CDR-H3 of SEQ ID NO: 28, the CDR-L1 of SEQ ID NO: 29, the CDR-L2 of SEQ ID NO: 30, and the CDR-L3 of SEQ ID NO: 31; (vi)the amino acid sequence of SEQ ID NO: 2;(vii) the amino acid sequence of SEQ ID NO: 46;(viii) the heavy chain variable region (HCVR) of SEQ ID NO: 35 and the light chain variable region (LCVR) of SEQ ID NO: 36;(ix) the HCVR of SEQ ID NO: 37 and the LCVR of SEQ ID NO: 36;(x)the HCVR of SEQ ID NO: 38 and the LCVR of SEQ ID NO: 39;(xi) the HCVR of SEQ ID NO: 40 and the LCVR of SEQ ID NO: 41;(xii) the HCVR of SEQ ID NO: 42 and the LCVR of SEQ ID NO: 43; or (xiii) the HCVR of SEQ ID NO: 44 and the LCVR of SEQ ID NO: 45;(b) the complement C5 inhibitor comprises Eculizumab or a biosimilar thereof, Nomacopan, Zilucoplan, Cemdisiran, Zimura, Ravulizumab, SOBI005, Tesidolumab, Pozelimab, or Crovalimab;(c) the complement C5 inhibitor is a nucleic acid molecule, and the nucleic acid molecule is selected from the group consisting of small interfering RNA, short hairpin RNA, micro RNA, and antisense oligonucleotide; or (d) the complement C5 inhibitor is an aptamer, and the aptamer is Avacincaptad Pegol.
6. - 9. (Cancelled)
10. (Currently Amended) The method of Claim 9 Claim 5,wherein;(a) the complement C5 inhibitor is a nucleic acid molecule, and the nucleic acid molecule is complementary to a portion of an endogenous nucleic acid sequence encoding complement C5, or(b) the complement C5 inhibitor is an anti-C5 antibody or antigen-binding fragment thereof, wherein the antigen-binding fragment comprises CDRH1-3 and CDRL1-3.
11. - 14. (Cancelled)
15. (Currently Amended) The method of any one of Claims 1 and 4-14 Claim 1, wherein the method is for treating SCD in the subject, wherein:(a) the SCD comprises hemolytic anemia or an acute vaso-occlusion (VOC) event; (b) the subject having SCD is diagnosed as having a mutation in the p globin gene;(c) the SCD comprises complement deposition in red blood cells (RBC); or (d) the SCD comprises intravascular hemolysis (IVH).
16. (Currently Amended) The method of The method of
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Reply to Office Notice of July 12, 2024 (a)the SCD comprises hemolytic anemia or an acute VOC event, and the subject presents with abdominal meteorism, right upper quadrant pain, or acute painful hepatomegaly;(b)the mutation in the globin gene is a single nucleotide mutation in the p globin gene;(c)the SCD comprises C5b9 deposition in RBC; or (d)IVH is characterized by an increase in at least one marker comprising lactate dehydrogenase (LDH), bilirubin, free hemoglobin, and free heme.
17. (Currently Amended) The method of Claim 1 (a)the subiect presents with abdominal meteorism, right upper quadrant pain, or acute painful hepatomegaly, and the VOC event is a lung VOC and/or a liver VOC, or(b)the single nucleotide mutation in the p globin gene results in a glutamic acid substitution by valine at position 6, relative to SEQ ID NO: 1.
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18. (Original) The method of Claim 17, wherein:(a) the lung VOC manifests as acute chest syndrome (ACS) and/or chronic lung disease; and/or (b) the liver VOC manifests as severe abdominal pain and/or liver dysfunction.
19. (Cancelled)
20. (Currently Amended) The method of Claim 19 Claim 4,wherein;(a the human patient is under 18 years of age;and/or (b)the SCD phenotype comprises increased inflammation or cytotoxicity leading to vascular tissue damage; enhanced pain triggered by VOC events; or increases in mortality or morbidity of SCD patients.
21. - 30. (Cancelled)
31. (Original) A method for improving viability or reducing death of cells under hypoxic conditions comprising contacting the cells with an effective amount of a composition comprising a complement inhibitor.
32. (Currently Amended) The method of The method of
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(a the cells are contacted in vivo;(b)the cells are sickle cells; and/or (c)the complement inhibitor is a complement C5 inhibitor.
33. (Cancelled)
34. (Currently Amended) The method of Claim 33 Claim 32,wherein the complement C5 inhibitor is selected from the group consisting of an anti-C5 antibody or an antigen-binding fragment thereof, a peptide, a small molecule, a nucleic acid molecule, and an aptamer.
35. (Currently Amended) The method of any one of the aforementioned Claims Claim 1,wherein SCD is characterized by a feature selected from:a. increased deposition of complement C3 and/or C5b9 in affected cells (e.g., RBCs), especially under a trigger (e.g., hypoxia); b. increased neovascular hemolysis, especially under a trigger (e.g., hypoxia), wherein increased hemolysis is characterized by increases in plasma LDH activity/levels, free heme and/or free hemoglobin levels, and/or total bilirubin levels; or c. increased severity of VOC, especially under a trigger (e.g., hypoxia).
36. (Currently Amended) The method of any one of the aforementioned Claims Claim 1,wherein treatment with a complement C5 inhibitor, such as an anti-C5 antibody results in an outcome selected from:a. inhibition or reversal of complement fragment deposition of C3 and C5b9 in RBCs of the subject with SCD, e.g., under hypoxic conditions; b. attenuation or reversal in the level of intravascular hemolysis under hypoxic conditions (as measured increases in plasma LDH activity/levels, free heme and/or free hemoglobin levels, and/or total bilirubin levels); or c. reduction or reversal in vaso-occlusion in the vessels of vital organs such as lung, kidney, liver and spleen of the subject with SCD.
37. (Currently Amended) The method of Claim 36, wherein:(a) treatment with a complement C5 inhibitor, such as an anti-C5 antibody, provides comparable improvement in at least one outcome of (a)-(c) a. - c. compared to the outcome with a standard treatment comprising hydroxyurea; preferably, wherein the treatment with the complement C5 inhibitor results in an improvement in an at least one outcome from (a)-(c) compared to treatment with hydroxyurea(b)the complement C5 inhibitor is an anti-C5 antibody;(c)treatment with a complement C5 inhibitor results in inhibition or reversal of complement fragment deposition of C3 and C5b9 in RBCs of the subject with SCD under hypoxic conditions;Reply to Office Notice of July 12, 2024(d)treatment with a complement C5 inhibitor results in attenuation or reversal in the level of intravascular hemolysis under hypoxic conditions as characterized by increases in plasma LDH activity/levels, free heme and/or free hemoglobin levels, and/or total bilirubin levels; and/or (e)the vital organs are selected from the group consisting of lung, kidney, liver, and spleen.
38. - 43. (Cancelled)
44. (New) The method of Claim 35, wherein:(a) the affected cells are RBCs; (b) SCD is characterized by increased deposition of complement C3 and/or C5b9 in affected cells under a trigger; and/or (c) the trigger is hypoxia.
45. (New) The method of Claim 37, wherein treatment with the complement C5 inhibitor results in an improvement in an at least one outcome of a. - c. compared to treatment with hydroxyurea.
This is a provisional rejection.
Conclusion
12. No claims are allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643