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 .
Response to Amendment
Receipt of Arguments/Remarks filed on 01/23/2026 is acknowledged. Claim 45 was amended. Claims 45-48,51,55 and 56 are pending and under examination.
A second non-final office action is being issued due to a new NSDP rejection over copending application (18/862,079), filed 10/31/2024, that is not necessitated by amendment.
Priority
This application is a CON of 16/308,007, filed 12/07/2018 which is now U.S. Patent No. 10946036, which is a 371 of PCT/US2017/037332 filed 06/13/2017, which claims benefit of 62/512,254 filed 05/30/2017, and claims benefit of 62/486,934 filed 04/18/2017, 62/470,157 filed 03/10/2017 and 62/349,596 filed 06/13/2016.
Response to Arguments
Applicant’s arguments and amendments, see pages 5-6, filed 01/23/2026, with respect to the claim interpretation provided by the examiner, have been fully considered, and are persuasive as applicant amended claim 45 to include in the preamble that the subject is a subject “in need thereof”, and therefore the administering step to the subject, would be to a subject in need thereof that is being treated for ambulatory spinal muscular atrophy, and defines a specific patient population. Therefore, the previous claim interpretation as treating any subject or administering the same amount of the same antibody to any subject no longer applies as the amendment requires treating and administering the effective amount of the recited antibody to a subject in need thereof, which would be a subject having ambulatory spinal muscular atrophy. Per MPEP 2111.02, See also Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333, 68 USPQ2d 1154, 1158 (Fed. Cir. 2003) (In considering the effect of the preamble in a claim directed to a method of treating or preventing pernicious anemia in humans by administering a certain vitamin preparation to "a human in need thereof," the court held that the claims’ recitation of a patient or a human "in need" gives life and meaning to the preamble’s statement of purpose).
Applicant’s arguments, see page 7, filed 01/23/2026, with respect to the 35 U.S.C. 112(d) rejection of claim 46 have been fully considered and are persuasive. Applicant explained the as-filed specification in paragraph 118 supports that ambulatory forms of SMA include ambulatory type III and type IV SMA and therefore type III SMA is further limiting since type III SMA represents a subset of ambulatory SMA. The 35 U.S.C. 112(d) rejection of claim 46 has been withdrawn.
Applicant’s arguments and amendments, see page 7, filed 01/23/2026, with respect to the 35 U.S.C. 102(a)(2) rejections of claims 45-47,55 and 56 as anticipated by Straub et al. (US 20170333558) and anticipated by Carven et al. (US 20180344844) have been fully considered and are persuasive due to the amendment to the preamble of claim 45 to require the treatment to be in a subject in need thereof, which requires treatment of a specific patient population. Therefore, the 35 U.S.C. 102 (a)(2) rejections of claims 45-47,55 and 56 have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of a case of obviousness. See the new 103 rejections below.
Applicant’s arguments and amendments, see pages 9-10, filed 01/23/2026 with respect to the non-statutory double patenting rejection over claims 1-11 of U.S. Patent No. 10,287,345, have been fully considered and are persuasive due to the amendment to the preamble requiring treating a subject in need thereof, which defines a specific patient population. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of a case of obviousness type double-patenting.
Drawings
The drawings are objected to because all of the figures are labeled as “Figure 1”, “Figure 2A”, etc. Figures should be labeled as “FIG. 1”, “FIG. 2A”, for example. See 37 CFR 1.84 (u) Numbering of views.
(1) The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation "FIG." must not appear.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 45-48,51,55 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Straub et al. (US 20170333558, filed 6 Nov 2015), cited on an IDS dated 02/03/2021, in view of US 20160074474 (‘474), Published 17 March 2016, previously cited.
Regarding claim 45, Straub et al. teach a method of treating a subject having a myopathy, the method comprising administering to the subject an effective amount of an antibody described above, and in embodiments the myopathy is spinal muscular atrophy (paragraph 0149). Straub et al. teach the effective amount of the antibody may range from about any of 0.1 μg/kg to 3 μg/kg to 30 μg/kg to 300 μg/kg to 3 mg/kg, to 30 mg/kg (paragraph 0164). The instant specification discloses the effective amount of SRK-015 for administration in human patients for the treatment of SMA ranges between 1 and 30 mg/kg, e.g., 1-5 mg/kg, 3-5 mg/kg, 3-10 mg/kg, 5-10 mg/kg, 5-15 mg/kg, 5-20 mg/kg, 10-20 mg/kg, etc. (paragraph 101). Therefore, Straub et al. discloses an effective amount of the antibody that is within the disclosed range of the dosage amount of the instant specification. Straub et al. teach the anti-pro/latent myostatin antibodies described herein are effective in treating a disease or disorder associated with myopathy (paragraph 0148). Straub et al. teaches an antibody that specifically binds to pro/latent-Myostatin compared with mature myostatin or compared to GDF11 (paragraph 0016). Straub et al. teaches anti-pro/latent Myostatin antibodies of the present disclosure and the nucleic acid molecules that encode the antibodies include the CDR amino acid sequences shown in Table 1, below (page 9):
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Table 1 and the CDR sequences above of Straub et al. are the same sequences disclosed in the instant specification in Table 1 on page 23 (see below) and which are now recited in instant claim 45:
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Straub et al. teach the antibody comprises six complementary determining regions (CDRs): CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 (paragraph 0085).
Straub et al. do not teach treating ambulatory spinal muscular atrophy in a subject in need thereof, or wherein the ambulatory SMA is type III SMA. Straub et al. do not teach wherein the subject has been determined to have two or more copies of a survival motor neuron 2 (SMN2) gene, or wherein the subject is a pediatric subject or young adult who is still growing and anabolically active.
However, before the effective filing date, ‘474 also teaches treating spinal muscular atrophy (Abstract). ‘474 teaches there are three types of SMA in terms of disease severity which are related to the expression of SMN2 in the subject, with Type I SMA characterized by early onset and death at less than 3 years of age, and never achieve the ability to sit, Type II SMA onset between 6-18 months of age and death at <30-40 years of age and associated with a SMN2 copy number of 2-3 and the type II subjects never achieve the ability to walk, and Type III SMA onset is typically at greater than 18 months of age with death at >60 and is associated with a SMN2 copy number of 3-4 [0060], and type III patients may be confined to a wheel chair by teenage (paragraph 0060). ‘474 teaches methods of treating a human with type III SMA, and treating a human that has an SMN2 copy number of 2-3 or 3-4 (paragraph 0061).
‘474 teaches the human is a pediatric subject or young adult (paragraph 0016), and that the pediatric subject is less than any one of 2 months of age, 3 months of age, 4 months of age, 5 months of age, 6 months of age, 7 months of age, 8 months of age, 9 months of age, 10 months of age, 11 months of age, 12 months of age, 13 months of age, 14 months of age, 15 months of age, 16 months of age, 17 months of age, 18 months of age, 1 year of age, 2 years of age, 3 years of age, 4 years of age, 5 years of age, 6 years of age, 7 years of age, 8 years of age, 9 years of age, 10 years of age, 11 years of age, 12 years of age, 13 years of age, 14 years of age, 15 years of age, 16 years of age, 17 years of age, 18 years of age. In some embodiments, the human subject is greater than 18 years of age (paragraph 0063).
Regarding claim 55, Straub et al. teach the amino acid sequences for the heavy chain variable region and light chain variable region of the antibodies listed in Table 1, and teaches SEQ ID NO: 25 as the heavy chain variable region (page 10) and SEQ ID NO: 31 as the light chain variable region (page 11) which are the same as instant SEQ ID NOs: 25 and 31 in claim 55.
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Regarding claim 56, Straub et al. teach the amino acid sequence for the heavy chain of SEQ ID NO: 50, and light chain of SEQ ID NO: 51 on pages 11-12 which are the same amino acid sequences of instant SEQ ID NOs: 50 and 51.
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Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the treatment method of Straub et al. and administer the antibody of Straub et al. to a subject in need thereof, which is a subject having type III SMA and wherein the method would treat ambulatory type III SMA based on the teachings of ‘474. There would be a reasonable expectation of success, because both Straub et al. and ‘474 pertain to treating SMA. One of ordinary skill in the art would have been motivated to administer the antibody of Straub et al. to a subject in need thereof having type III SMA, in order to treat type III SMA, because ‘474 teaches that type III SMA patients may be confined to a wheelchair by teenage, which indicates that they can walk up to this point, and ‘474 teaches methods of treating a human with type III SMA (paragraph 0061), and therefore it would be motivated to treat a subject that is ambulatory that is type III as the other types of SMA cannot walk, and the treatment of type III SMA would prevent the patient from losing mobility and becoming non-ambulatory, and would make obvious the limitations of claims 45-47,55 and 56.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the method of Straub et al. and to administer the antibody of Straub et al. to a subject having type III ambulatory SMA, that has been determined to have two or more copies of the SMN2 gene based on the teachings of ‘474 with a reasonable expectation of success. There would be a reasonable expectation of success, because both Straub et al. and ‘474 pertain to treating SMA. One of ordinary skill in the art would be motivated to administer the antibody of Straub et al. which is taught to treat SMA, to a subject having type III SMA and having been determined to have two or more copies of a SMN2 gene because ‘474 teaches Type III SMA is associated with a SMN2 copy number of 3-4 (paragraph 0060) and teaches methods of treating a human with type III SMA, and treating a human that has an SMN2 copy number of 2-3 or 3-4 (paragraph 0061), and therefore would be an obvious subject to treat with the antibody of Straub et al., and would make obvious the limitations of claim 48.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the method of Straub et al. to administer the antibody of Straub et al. to a pediatric subject or young adult having type III SMA, with a reasonable expectation of success for the purpose of treating ambulatory SMA at an early age. There would be a reasonable expectation of success, because both Straub et al. and ‘474 pertain to treating SMA. One of ordinary skill in the art would be motivated to administer the antibody of Straub et al. which is taught to treat SMA to a subject which is a pediatric or young adult subject because ‘474 teaches Type III SMA onset is typically at greater than 18 months of age, and teaches treating SMA in a human pediatric subject or young adult (paragraph 0016), and would make obvious the limitations of claim 51.
The applied reference has a common inventor and assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Response to Arguments
Applicant argues on page 9 of response, filed 01/23/2026, that claim 45 was not included in the rejection under 35 U.S.C. 103 and therefore independent claim 45 is not anticipated by Straub et al. or Carven et al. and since claims 46,48 and 51 depend from claim 45 and incorporate all limitations of that claim, the dependent claims are also novel and non-obvious for at least the same reasons and cites In re Fine and MPEP 2143.03.
This is not found persuasive, because claims 45-47,55 and 56 were rejected under 35 U.S.C. 102(a)(2) based on the claim interpretation regarding the preamble provided by the Examiner in the previous office action. Claims 46,48 and 51 were then rejected under 35 U.S.C. 103 as obvious over Straub et al. further in view of ‘474 and under 35 U.S.C. 103 as obvious over Carven et al. and further in view of ‘474. Claim 45 was not rejected under 35 U.S.C. 103 because it was anticipated by Straub et al. as well as Carven et al. However, based on the current amendment to claim 45 which defines the treatment of a specific patient population (a subject in need thereof), claims 45-47,55 and 56 can no longer be considered as anticipated by Straub et al. or Carven et al., and therefore, a new rejection, necessitated by amendment, under 35 U.S.C. 103 is needed based on a case of obviousness.
Claims 45-48,51,55 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Carven et al. (US 20180344844, EFD 15 Sept 2015), cited on an IDS dated 01/15/2025, in view of US 20160074474 (‘474), Published 17 March 2016, cited previously.
Regarding claims 45, Carven et al. teach a method of treating a subject having a myopathy, the method comprising administering to the subject an effective amount of an antibody described above, and in embodiments the myopathy is spinal muscular atrophy (paragraphs 0018,0049,0051). Carven et al. teach the effective amounts of the antibody may range from about any of 0.1 μg/kg to 3 μg/kg to 30 μg/kg to 300 μg/kg to 3 mg/kg, to 30 mg/kg (paragraph 0220). The instant specification discloses the effective amount of SRK-015 for administration in human patients for the treatment of SMA ranges between 1 and 30 mg/kg, e.g., 1-5 mg/kg, 3-5 mg/kg, 3-10 mg/kg, 5-10 mg/kg, 5-15 mg/kg, 5-20 mg/kg, 10-20 mg/kg, etc. (paragraph 101). Therefore, Carven et al. discloses an effective amount of the antibody that is within the disclosed range of the dosage amount of the instant specification and therefore anticipates the effective amount of the instant claims. Carven et al. teach the anti-pro/latent-myostatin antibodies described herein are effective in treating a disease or disorder associated with myopathy, including spinal muscular atrophy (paragraph 0200). Carven et al. teaches an antibody that specifically binds to pro/latent-Myostatin compared with mature myostatin or compared to GDF11 (paragraph 0015).
Carven et al. teaches anti-pro/latent Myostatin antibodies of the present disclosure and the nucleic acid molecules that encode the antibodies include the CDR amino acid sequences shown in Table 1, below (page 12, Paragraph 0135):
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Table 1 and the CDR sequences above of Carven et al. are the same sequences disclosed in the instant specification in Table 1 on page 23 (see below) and which are now recited in instant claim 45:
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Carven et al. teach the antibody comprises six complementary determining regions (CDRs): CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 (paragraph 00137).
Carven et al. do not teach treating ambulatory spinal muscular atrophy in a subject in need thereof, or wherein the ambulatory SMA is type III SMA. Carven et al. do not teach wherein the subject has been determined to have two or more copies of a survival motor neuron 2 (SMN2) gene, or wherein the subject is a pediatric subject or young adult who is still growing and anabolically active.
However, before the effective filing date, ‘474 also teaches treating spinal muscular atrophy (Abstract). ‘474 teaches there are three types of SMA in terms of disease severity which are related to the expression of SMN2 in the subject, with Type I SMA characterized by early onset and death at less than 3 years of age, and never achieve the ability to sit, Type II SMA onset between 6-18 months of age and death at <30-40 years of age and associated with a SMN2 copy number of 2-3 and the type II subjects never achieve the ability to walk, and Type III SMA onset is typically at greater than 18 months of age with death at >60 and is associated with a SMN2 copy number of 3-4 [0060], and type III patients may be confined to a wheel chair by teenage (paragraph 0060). ‘474 teaches methods of treating a human with type III SMA, and treating a human that has an SMN2 copy number of 2-3 or 3-4 (paragraph 0061).
‘474 teaches the human is a pediatric subject or young adult (paragraph 0016), and that the pediatric subject is less than any one of 2 months of age, 3 months of age, 4 months of age, 5 months of age, 6 months of age, 7 months of age, 8 months of age, 9 months of age, 10 months of age, 11 months of age, 12 months of age, 13 months of age, 14 months of age, 15 months of age, 16 months of age, 17 months of age, 18 months of age, 1 year of age, 2 years of age, 3 years of age, 4 years of age, 5 years of age, 6 years of age, 7 years of age, 8 years of age, 9 years of age, 10 years of age, 11 years of age, 12 years of age, 13 years of age, 14 years of age, 15 years of age, 16 years of age, 17 years of age, 18 years of age. In some embodiments, the human subject is greater than 18 years of age (paragraph 0063).
Regarding claim 55, Carven et al. teach the amino acid sequences for the heavy chain variable region and light chain variable region of the antibodies listed in Table 1, and teaches SEQ ID NO: 25 as the heavy chain variable region (page 13) and SEQ ID NO: 31 as the light chain variable region (page 14) which are the same as instant SEQ ID NOs: 25 and 31 in claim 55.
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Regarding claim 56, Carven et al. teach the amino acid sequence for the heavy chain of SEQ ID NO: 50, and light chain of SEQ ID NO: 51 on page 15 which are the same amino acid sequences of instant SEQ ID NOs: 50 and 51.
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Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the treatment method of Carven et al. and to administer the antibody of Carven et al. to a subject in need thereof, which is a subject having type III SMA (ambulatory) and wherein the method would treat type III SMA based on the teachings of ‘474. There would be a reasonable expectation of success, because both Carven et al. and ‘474 pertain to treating SMA. One of ordinary skill in the art would have been motivated to administer the antibody of Carven et al. to a subject having type III SMA, in order to treat type III SMA that is ambulatory, because ‘474 teaches that type III SMA patients may be confined to a wheelchair by teenage, which indicates that they can walk up to that point and teaches methods of treating a human with type III SMA, and therefore it would be obvious to treat a subject that has type III SMA which is ambulatory, which would prevent the patient from losing mobility and becoming non-ambulatory, and would make obvious the limitations of claims 45-47,55 and 56.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the method of Carven et al. and to administer the antibody of Carven et al. to a subject having type III SMA (ambulatory), that has been determined to have two or more copies of the SMN2 gene based on the teachings of ‘474 with a reasonable expectation of success. There would be a reasonable expectation of success, because both Carven et al. and ‘474 pertain to treating SMA. One of ordinary skill in the art would be motivated to administer the antibody of Carven et al. which is taught to treat SMA, to a subject having been determined to have two or more copies of a SMN2 gene because ‘474 teaches Type III SMA is associated with a SMN2 copy number of 3-4 (paragraph 0060) and teaches treating a human that has an SMN2 copy number of 2-3 or 3-4 (paragraph 0061), and would be an obvious subject to treat with the antibody of Carven et al. and would make obvious the limitations of claim 48.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the method of Carven et al. to administer the antibody of Carven et al. to a pediatric subject or young adult with a reasonable expectation of success for the purpose of treating type III SMA (ambulatory) at an early age. There would be a reasonable expectation of success, because both Carven et al. and ‘474 pertain to treating SMA. One of ordinary skill in the art would be motivated to administer the antibody of Carven et al. which is taught to treat SMA to a subject which is a pediatric or young adult subject because ‘474 teaches Type III SMA onset is typically at greater than 18 months of age, and teaches treating SMA in a human pediatric subject or young adult (paragraph 0016) and would make obvious the limitations of claim 51.
Accordingly, the claims 45-48,51,55 and 56 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
The applied reference has a common inventor and assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Response to Arguments
Applicant argues on page 9 of response, filed 01/23/2026, that claim 45 was not included in the rejection under 35 U.S.C. 103 and therefore independent claim 45 is not anticipated by Straub et al. or Carven et al. and since claims 46,48 and 51 depend from claim 45 and incorporate all limitations of that claim, the dependent claims are also novel and non-obvious for at least the same reasons and cites In re Fine and MPEP 2143.03.
This is not found persuasive, because claims 45-47,55 and 56 were rejected under 35 U.S.C. 102(a)(2) based on the claim interpretation regarding the preamble provided by the Examiner in the previous office action. Claims 46,48 and 51 were then rejected under 35 U.S.C. 103 as obvious over Straub et al. further in view of ‘474 and under 35 U.S.C. 103 as obvious over Carven et al. and further in view of ‘474. Claim 45 was not rejected under 35 U.S.C. 103 because it was anticipated by Straub et al. as well as Carven et al. However, based on the current amendment to claim 45 which defines the treatment of a specific patient population (a subject in need thereof), claims 45-47,55 and 56 can no longer be considered as anticipated by Straub et al. or Carven et al., and therefore, a new rejection, necessitated by amendment, under 35 U.S.C. 103 is needed based on a case of obviousness.
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 45-48,51,55 and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,287,345 (‘345), Issued 14 May 2019, in view of US 20160074474 (‘474), Published 17 March 2016.
Instant claims 45-48 and 51 recite a method of treating ambulatory spinal muscular atrophy in a subject in need thereof, the method comprising administering to the subject a selective myostatin inhibitor that binds to pro/latent myostatin but does not bind to mature myostatin or GDF-11 in an amount effective to treat ambulatory SMA, wherein the selective myostatin inhibitor comprises an antibody or antigen-binding fragment thereof comprising six complementarity determining regions (CDRs): CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 wherein: a) CDRH1 comprises the amino acid sequence of SEQ ID NO: 1, CDRH2 comprises the amino acid sequence of SEQ ID NO: 4, CDRH3 comprises the amino acid sequence of SEQ ID NO: 10, CDRL1 comprises the amino acid sequence of SEQ ID NO: 12, CDRL2 comprises the amino acid sequence of SEQ ID NO: 18, and CDRL3 comprises the amino acid sequence of SEQ ID NO: 22, wherein the CDR sequences are numbered according to Kabat numbering system. Instant claim 55 recites the heavy chain variable domain comprises SEQ ID NO: 25 and light chain variable domain comprises SEQ ID NO: 31, and instant claim 56 recites heavy chain amino acid sequence of SEQ ID NO: 50 and light chain comprising amino acid sequence of SEQ ID NO: 51. The instant specification discloses the effective amount of SRK-015 for administration in human patients for the treatment of SMA ranges between 1 and 30 mg/kg, e.g., 1-5 mg/kg, 3-5 mg/kg, 3-10 mg/kg, 5-10 mg/kg, 5-15 mg/kg, 5-20 mg/kg, 10-20 mg/kg, etc. (paragraph 101).
Claims 1-11 of the ‘345 patent are directed to a method for inhibiting myostatin activation in a subject comprising a step of administering to the subject a composition comprising an antibody or an antigen-binding fragment thereof, that specifically binds pro-myostatin and latent myostatin and blocks release of mature myostatin in an amount effective to cause two or more of the following in the subject: (a) an increase in mass and/or function of a muscle tissue in the subject and (d) prevention of muscle loss or atrophy in the subject, and recites the antibody with the same CDR SEQ ID NOs as instant claim 45 (SEQ ID NOs: 1,4,10,12,18 and 22) and same heavy chain variable region and light chain variable region sequences as in instant claim 55 (SEQ ID NOs: 25 and 31). Claim 4 of the ’345 patent recites the subject has muscular atrophy associated with spinal muscular atrophy. ‘345 discloses an effective amount of the antibody to be from about any of 0.1 μg/kg to 3 μg/kg to 30 μg/kg to 300 μg/kg to 3 mg/kg, to 30 mg/kg (Column 85, lines 8-9).
While ‘345 recites the subject has a muscle atrophy which is associated with spinal muscular atrophy, ‘345 does not recite treating ambulatory spinal muscular atrophy in a subject in need thereof.
The teachings of ‘474 have been described above in the 103 rejections.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the method of ‘345 based on the teachings of ‘474 to administer the antibody to a subject in need thereof, which is a subject having ambulatory SMA and wherein the method would treat ambulatory type III SMA. One of ordinary skill in the art would have been motivated to do so because ‘474 teaches that type III SMA patients may be confined to a wheelchair by teenage, which indicates that they can walk up to this point, and therefore it would be obvious to treat a subject that is ambulatory that is type III as the other types of SMA cannot walk, and the treatment of type III SMA would prevent the patient from losing mobility and becoming non-ambulatory, and would make obvious the limitations of claims 45-47,55 and 56.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the method of ‘345 and to administer the antibody to a subject having ambulatory SMA, that has been determined to have two or more copies of the SMN2 gene based on the teachings of ‘474 with a reasonable expectation of success. One of ordinary skill in the art would be motivated to do so because ‘474 teaches Type III SMA is associated with a SMN2 copy number of 3-4 (paragraph 0060), and would be an obvious subject to treat with the antibody of Carven et al. and would make obvious the limitations of claim 48.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the method of ‘345 and to administer the antibody to a pediatric subject or young adult with a reasonable expectation of success for the purpose of treating ambulatory SMA at an early age. One of ordinary skill in the art would be motivated to do so because ‘474 teaches Type III SMA onset is typically at greater than 18 months of age, and teaches treating SMA in a human pediatric subject or young adult (paragraph 0016) and would make obvious the limitations of claim 51.
Claims 45-48,51,55 and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-48 of copending Application No. 18/250,489 (‘489) (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. Instant claims 45-48 and 51 recite a method of treating ambulatory spinal muscular atrophy in a subject in need thereof, with claim 46 reciting the ambulatory SMA is type III SMA, the method comprising administering to the subject a selective myostatin inhibitor that binds to pro/latent myostatin but does not bind to mature myostatin or GDF-11 in an amount effective to treat ambulatory SMA, wherein the selective myostatin inhibitor comprises an antibody or antigen-binding fragment thereof comprising six complementarity determining regions (CDRs): CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 wherein: a) CDRH1 comprises the amino acid sequence of SEQ ID NO: 1, CDRH2 comprises the amino acid sequence of SEQ ID NO: 4, CDRH3 comprises the amino acid sequence of SEQ ID NO: 10, CDRL1 comprises the amino acid sequence of SEQ ID NO: 12, CDRL2 comprises the amino acid sequence of SEQ ID NO: 18, and CDRL3 comprises the amino acid sequence of SEQ ID NO: 22, wherein the CDR sequences are numbered according to Kabat numbering system. Instant claim 55 recites the heavy chain variable domain comprises SEQ ID NO: 25 and light chain variable domain comprises SEQ ID NO: 31, and instant claim 56 recites heavy chain amino acid sequence of SEQ ID NO: 50 and light chain comprising amino acid sequence of SEQ ID NO: 51. The instant specification discloses the effective amount of SRK-015 for administration in human patients for the treatment of SMA ranges between 1 and 30 mg/kg, e.g., 1-5 mg/kg, 3-5 mg/kg, 3-10 mg/kg, 5-10 mg/kg, 5-15 mg/kg, 5-20 mg/kg, 10-20 mg/kg, etc. (paragraph 101).
Claims 25-48 of ‘489 recite a method of treating spinal muscular atrophy in a human subject in need thereof comprising administering apitegromab in an amount greater than 2mg/kg and no more than 20mg/kg and therefore anticipates the instant disclosed effective amount above. Claims 38 and 48 of ‘489 recite the SMA is ambulatory type 3 SMA as in instant claim 46, claim 41 of ‘489 recites the subject has at least two copies of the SMN2 gene as in instant claim 48, and claims 32-35 of ‘489 recite the ages of the subject falling within the pediatric subject or young adult in instant claim 51. The specification of ‘489 defines Apitegromab as also being referred to as SRK-015, and is a fully human monoclonal antibody that specifically binds to the proforms of myostatin, namely promyostatin and latent myostatin, with high affinity thereby inhibiting myostatin activation, and that Apitegromab is a selective myostatin inhibitor (page 13, paragraph 66). The specification of ‘489 discloses amino acid sequences of the anti-pro/latent myostatin antibody of the CDR regions, variable regions and full-length heavy and light chains in Tables 1,2,3A and 3B on pages 30-31 that are the same as the instantly claimed sequences. Note the SEQ ID NOs differ but the sequences themselves are the same.
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Therefore, as the claims of ‘489 recite treating SMA by administering the same effective amount of an antibody (apitegromab) defined and disclosed as having the same sequences as the instantly claimed antibody sequences, is also claimed for treating ambulatory type III SMA, and claims the subject having the age range of a pediatric or young adult, the instant claims are not patentably distinct from the claims of ‘489.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 01/23/2026 have been fully considered but they are not persuasive.
Applicant argues on page 10 of response, that they disagree with the rejection, and pursuant to MPEP 804 because the present application has the earlier patent term filing date and Applicant contends the submitted remarks address all other rejections by the Office, the Examiner should withdrawn this provisional double patenting rejection.
This is not found persuasive, because the claims are still rejected and not in condition for allowance, which was necessitated by amendment, and according to MPEP 804, it is only when the provisional nonstaturoy double patenting rejection is the only remaining rejection in an application having the earlier patent term filing date, that the examiner should withdraw the rejection. Therefore, this provisional nonstatutory double patenting rejection stands.
New Nonstatutory Double Patenting Rejection not necessitated by Amendment
Claims 45-48,51,55 and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22,28-31,35-50 of copending Application No. 18,862,079 (‘079), filed 10/31/2024.
Instant claims 45-48 and 51 recite a method of treating ambulatory spinal muscular atrophy in a subject in need thereof, the method comprising administering to the subject a selective myostatin inhibitor that binds to pro/latent myostatin but does not bind to mature myostatin or GDF-11 in an amount effective to treat ambulatory SMA, wherein the selective myostatin inhibitor comprises an antibody or antigen-binding fragment thereof comprising six complementarity determining regions (CDRs): CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 wherein: a) CDRH1 comprises the amino acid sequence of SEQ ID NO: 1, CDRH2 comprises the amino acid sequence of SEQ ID NO: 4, CDRH3 comprises the amino acid sequence of SEQ ID NO: 10, CDRL1 comprises the amino acid sequence of SEQ ID NO: 12, CDRL2 comprises the amino acid sequence of SEQ ID NO: 18, and CDRL3 comprises the amino acid sequence of SEQ ID NO: 22, wherein the CDR sequences are numbered according to Kabat numbering system. Instant claim 55 recites the heavy chain variable domain comprises SEQ ID NO: 25 and light chain variable domain comprises SEQ ID NO: 31, and instant claim 56 recites heavy chain amino acid sequence of SEQ ID NO: 50 and light chain comprising amino acid sequence of SEQ ID NO: 51. The instant specification discloses the effective amount of SRK-015 for administration in human patients for the treatment of SMA ranges between 1 and 30 mg/kg, e.g., 1-5 mg/kg, 3-5 mg/kg, 3-10 mg/kg, 5-10 mg/kg, 5-15 mg/kg, 5-20 mg/kg, 10-20 mg/kg, etc. (paragraph 101).
Claims 22,31 and 35-50 of ‘079 recite a method of treating spinal muscular atrophy in a subject who receives survival motor neuron therapy, comprising administering an effective amount of apitegromab to a subject, wherein the subject suffers from fatigue, impaired bulbar function, and/or impaired emptying. Claim 28 recites wherein the subject has type 3 SMA, has 2,3,4 or 5 copies of the SMN2 gene, the subject has ambulatory SMA, and/or the subject is 2 years of age or older at the time of starting administration of the myostatin inhibitor. Claim 29 recites the subject is 2-12 years of age, and claim 30 the subject is 2-21 years of age. Claims 48-49 recite the effective amount of apitegromab adiministered is 10 mg/kg and 20 mg/kg.
The specification of ‘079 defines Apitegromab as also being referred to as SRK-015, and is a fully human monoclonal antibody that specifically binds to the proforms of myostatin, namely promyostatin and latent myostatin, with high affinity thereby inhibiting myostatin activation, and that Apitegromab is a selective myostatin inhibitor (page 13, paragraph 72). The specification of ‘079 discloses amino acid sequences of the anti-pro/latent myostatin antibody of the CDR regions, variable regions and full-length heavy and light chains in Tables 1,2,3,4 on pages 28-29 that are the same as the instantly claimed sequences. Note the SEQ ID NOs differ but the sequences themselves are the same.
Therefore, as the claims of ‘079 recite treating SMA by administering the same effective amount of an antibody (apitegromab) defined and disclosed as having the same sequences as the instantly claimed antibody sequences, is also claimed for treating ambulatory type III SMA, and claims the subject having the age range of a pediatric or young adult, the instant claims are not patentably distinct from the claims of ‘489.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 45-48,51,55 and 56 are rejected.
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/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636