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 .
Election/Restrictions and Claim Status
Applicants’ arguments filed 2/26/26 are acknowledged.
Previously, subject diagnosed as having AMD, AREDS2 vitamin supplement and diphenhydramine were elected.
The restriction requirement stated: ‘If a subject with a specific feature as in claims 13-19 is intended then such subject should be specifically identified’. Since the specification (page 32) expressly states that exudative AMD is an exclusion criteria and GA is an inclusion criteria as well as LL-BCVA deficit (page 31), claims 16 and 19 are drawn to non-elected species.
Although applicants argue that patients can have more than one feature, what was elected was a subject having AMD.
Since applicants elected AREDS2 vitamin supplement and diphenhydramine, claims 22-23 and 26 are drawn to non-elected species.
Claims 16, 19, 22-23 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/25/24.
Claims 1, 4-15 and 27-28 have been canceled.
Claims 2-3, 17-18, 20-21 and 24-25 are being examined.
Priority
The priority information is found in the filing receipt dated 4/10/24.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/26/26 and 1/5/26 have been considered by the examiner.
Claim Rejections - 35 USC § 103
The 103 rejection is maintained from the previous office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2-3, 17-18, 20-21 and 24-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Reclaim 2 Data Slides (retrieved from https://stealthbt.com/wp-content/uploads/ClinTrial@Summit_Heier_ReCLAIM-2-presentation-final.5.21.pdf on 7/5/24, 20 pages; ‘Reclaim2’) in view of Clinical Trails (Clinical Trails entry for NCT03891875, retrieved from https://clinicaltrials.gov/study/NCT03891875?tab=history&a=25#version-content-panel on 7/5/24, 21 pages; ‘NCT03891875’) in view of Gorusupudi et al. (‘The age-related eye disease 2 study: micronutrients in the treatment of macular degeneration’ Adv Nutr v8 2017 pages 40-53; ‘Gorusupudi’) in view of Kaiser et al. (‘Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations’ Rheumatol Int v32 2012 pages 295-299; ‘Kaiser’).
The Wayback machine entry for Reclaim 2 Data slides (retrieved from https://web.archive.org/web/20220614080035/https://stealthbt.com/presentations/ on 7/9/24, 2 pages) reveals that the Reclaim2 document was available on-line as of June 14 2022 (page 1).
Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20). Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12). Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17).
NCT03891875 teach a study to evaluate elamipretide in subjects with AMD with non-central GA (page 6 section ‘brief title’). As set forth on page 1 of the document, various versions of the study are available. As set forth on page 6 of the document, the version provided corresponds to the version dated May 25 2022 (version 25). NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide for 48 weeks (page 10 section ‘Arms and Interventions’). NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’) and recognizes exclusion of exudative AMD (page 13).
Reclaim2 and NCT03891875 do not recite administration for 96 weeks as in claim 20 or the details of claims 21, 24 and 25.
Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1). Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract). Gorusupudi teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1).
Kaiser teach that injection site reactions is a common adverse event associated with different kinds of biologics (page 295 last paragraph). Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that
diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph). Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Reclaim2 because Reclaim2 teach the potential to improve LLVA in patients with GA secondary to dry AMD (page 19). Thus one would have been motivated to use known methods (details provided in NCT03891875) along with known agents (AREDS2 as taught by Gorusupudi, compare MPEP 2144.06) for treating dry AMD. Further, since Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12) one would have been motivated to use the known agents and techniques taught by Kaiser. With respect to the length of administration, Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years. One would have had a reasonable expectation of success because Reclaim2 teach elamipretide mediated reduction of progressive EZ attenuation correlates with visual function improvements (page 20). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5).
In relation to the administering of claim 2, NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide (page 10 section ‘Arms and Interventions’).
Claim 2 recites ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines). MPEP 2111.02 recognizes that statements reciting the purpose or intended use must be evaluated to determine whether or not the purpose or intended use result in a manipulative difference. In the instant case, the recitation ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines) do not result in a manipulative difference. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for such intended use and purpose.
In relation to the subjects of claims 2 and 17-18, NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’). Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). NCT03891875 recognizes exclusion of exudative AMD (page 13) thus teaching no-exudative AMD. Applicants own specification recognizes GA involves irreversible loss of visual function (section 0003).
In relation to the time frame of claim 2 and 20, Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years.
Claim 3 refers to the area or changes of tEZa. Such claim is referring back to the intended uses as recited in claim 2 (i.e. ‘to reduce the rate’ as recited in the last 4 lines). As currently claimed, the required active method step is ‘administering’. Whether or not the intent or purpose is to reduce the rate in a particular way does not change the fact that the intended use or purpose does not require a manipulative difference (see MPEP 2111.02 II). Stated another way, independent of how the intended reduction is intended to be assessed, the active step as currently claimed remains administering. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for the claimed intended use and purpose. Further, NCT03891875 expressly recites measurements using optical coherence tomography (page 11 section ‘primary outcome measures’). In addition, Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20).
In relation to claim 21, Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1).
In relation to claim 24, Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
In relation to claim 25, Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph).
Response to Arguments - 103
Applicant's arguments filed 2/26/26 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants refer to previous arguments, all previous arguments and affidavit related to the instant 103 rejection have been considered and are not found persuasive. The response to the arguments and affidavit as set forth in the previous office action are reproduced below.
Although applicants argue that it would be inappropriate to decline to consider the intended use and purpose, MPEP 2111.02 recognizes that statements reciting the purpose or intended use must be evaluated to determine whether or not the purpose or intended use result in a manipulative difference. In the instant case, the recitation ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines) do not result in a manipulative difference. Applicants do not appear to have made any arguments related as to any possible manipulative difference of the phrase ‘of reducing’ or ‘to reduce’. As currently claimed, the required active method step is ‘administering’. Whether or not the intent or purpose is to reduce the rate in a particular way does not change the fact that the intended use or purpose does not require a manipulative difference (see MPEP 2111.02 II). Stated another way, independent of how the intended reduction is intended to be assessed, the active step as currently claimed remains administering.
Although applicants argue via the arguments and declaration that ‘a person of ordinary skill in the art would not have known or expected that a linear rate of therapeutic benefit would be achieved’, MPEP 2143.02 I states: “The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention”. In the instant case, as discussed in detail above the claim limitations (specifically the step of administrating) are met. The instant claims are not drawn to data analysis. Although applicants appear to suggest that precise knowledge of the exact numerical value of certain measured variables is required, that is not the standard. In fact, MPEP 2143.02 II states that: “Obviousness does not require absolute predictability”. In the instant case, Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17).
Although applicants argue via the arguments and declaration about increasing a dose from 40 mg to 60 mg, it is first noted that the instant claims require 40 mg once every day not 60 mg. Further, there do not appear to be any details provided other than a clinical trial number. Important to the facts of this case, NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide for 48 weeks (page 10 section ‘Arms and Interventions’).
Although applicants argue via the arguments and declaration about ‘seeking to produce a linear rate of therapeutic benefit’, MPEP 2144 IV recognizes that the reason to modify a reference does not have to be the same and that it is not necessary that the prior art suggest the advantage or result discovered. In the instant case, Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years.
Although applicants argue via the arguments and declaration that one would not have had an expectation for how the tEZa parameter changes over time, MPEP 2143.02 I states: “The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention”. The instant claims are not drawn to evaluating the tEZa parameter over time. The active step of claim 2 is ‘administering’. Further, MPEP 2144 IV recognizes that it is not necessary that the prior art suggest the advantage or result discovered.
Although applicants argue via the arguments and declaration that without the data analysis one would not have understood the constant linear therapeutic benefit, MPEP 2143.02 II states that: “Obviousness does not require absolute predictability”. Obviousness does not require proof of a constant, linear therapeutic benefit. Reclaim2 relates to a phase 2 study (slide 1) and refers to phase 1 clinical trials (slide 8). MPEP 2107.03 IV states: “Before a drug can enter human clinical trials, the sponsor, often the applicant, must provide a convincing rationale to those especially skilled in the art (e.g., the Food and Drug Administration (FDA)) that the investigation may be successful. Such a rationale would provide a basis for the sponsor’s expectation that the investigation may be successful. In order to determine a protocol for phase I testing, the first phase of clinical investigation, some credible rationale of how the drug might be effective or could be effective would be necessary. Thus, as a general rule, if an applicant has initiated human clinical trials for a therapeutic product or process, Office personnel should presume that the applicant has established that the subject matter of that trial is reasonably predictive of having the asserted therapeutic utility.”
Although applicants argue via the arguments and declaration that the FDA stated that further analysis is needed to determine the best fit curve, MPEP 2107.03 V recognizes that ‘The Office must confine its review of patent applications to the statutory requirements of the patent law’. Importantly, MPEP 2143.02 II states that: “Obviousness does not require absolute predictability”. Obviousness does not require that a best fit curve must be established before an experiment is conducted.
Although applicants argue via the arguments and declaration that analysis of data from the trial may result in the next trial being held at a higher dose, MPEP 2107.03 V recognizes that ‘The Office must confine its review of patent applications to the statutory requirements of the patent law’. The requirements for a clinical trial are not the same as what is required for a reasonable expectation of success (see MPEP 2143.02).
Although applicants allude to ‘unexpected benefits’ (page 10 of the 5/2/25 reply), Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Thus, the peptide recited in the claim and its beneficial effects were known. MPEP 716.02(b) recognizes that the burden is on the applicant to establish results are unexpected and significant. MPEP 716.02(e) refers to a comparison to the closest prior art. In the instant case, it is unclear what comparison is being made (if any). The specification implies that when administered daily that the benefit is continuous and sustained (page 39 of the specification). One would not necessarily recognize such result as unexpected. It appears that no difference in kind (see MPEP 716.02) is suggested. It is not even clear that a difference in degree is suggested. Piccardi et al. (‘A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration:sustained benefits to central retinal function’ Evidenced based complementary and alternative medicine 2012 pages 1-9) teach a treatment of age-related macular degeneration for 14 months that provided sustained benefits (abstract and title) and specifically refers to protecting photoreceptors from retinal stress and maintaining morphology and function (page 2 first complete paragraph). There are inadequate facts to conclude unexpected results.
In summary, the affidavit under 37 CFR 1.132 filed 5/2/25 is insufficient to overcome the rejection of claims set forth above under 103 as set forth in the last Office action because: MPEP 2143.02 II states that: “Obviousness does not require absolute predictability”. The affidavit appears to suggest a completely different standard – absolute predictability specifically with respect to determination of a linear trend. Further, the requirements for a clinical trial are not the same as what is required for a reasonable expectation of success (see MPEP 2143.02). As discussed in detail above, the peptide recited in the claim and its beneficial effects were known. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Double Patenting
The double patenting rejections from the previous office action are maintained.
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 2-3, 17-18, 20-21 and 24-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,944,662 (662) in view of Reclaim 2 Data Slides (retrieved from https://stealthbt.com/wp-content/uploads/ClinTrial@Summit_Heier_ReCLAIM-2-presentation-final.5.21.pdf on 7/5/24, 20 pages; ‘Reclaim2’) in view of Clinical Trails (Clinical Trails entry for NCT03891875, retrieved from https://clinicaltrials.gov/study/NCT03891875?tab=history&a=25#version-content-panel on 7/5/24, 21 pages; ‘NCT03891875’) in view of Gorusupudi et al. (‘The age-related eye disease 2 study: micronutrients in the treatment of macular degeneration’ Adv Nutr v8 2017 pages 40-53; ‘Gorusupudi’) in view of Kaiser et al. (‘Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations’ Rheumatol Int v32 2012 pages 295-299; ‘Kaiser’).
662 recites a method for treating age-related macular degeneration (specifically dry ARMD) comprising administering a specific peptide (claim 1). 622 recites details about the subject (claims 2-4) and administration (claim 5) as well as additional agents (claims 7-9).
662 does not recite all of the specific details of the instant claims such as the specific amount administered.
The Wayback machine entry for Reclaim 2 Data slides (retrieved from https://web.archive.org/web/20220614080035/https://stealthbt.com/presentations/ on 7/9/24, 2 pages) reveals that the ReCLAIM-2 document was available on-line as of June 14 2022 (page 1).
Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20). Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12). Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17).
NCT03891875 teach a study to evaluate elamipretide in subjects with AMD with non-central GA (page 6 section ‘brief title’). As set forth on page 1 of the document, various versions of the study are available. As set forth on page 6 of the document, the version provided corresponds to the version dated May 25 2022 (version 25). NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide for 48 weeks (page 10 section ‘Arms and Interventions’). NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’) and recognizes exclusion of exudative AMD (page 13).
Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1). Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract). Gorusupudi teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1).
Kaiser teach that injection site reactions is a common adverse event associated with different kinds of biologics (page 295 last paragraph). Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that
diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph). Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 662 because 662 teach methods of treating ARMD with a specific peptide (which is elamipretide see section 0036 of the instant specification) so one would have been motivated to use known methods (details provided in NCT03891875) along with known agents (AREDS2 as taught by Gorusupudi, compare MPEP 2144.06) for treating AMD. Further, since Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12) one would have been motivated to use the known agents and techniques taught by Kaiser. With respect to the length of administration, Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years. One would have had a reasonable expectation of success because 662 expressly teach for treating ARMD (claim 1) and Reclaim2 teach elamipretide mediated reduction of progressive EZ attenuation correlates with visual function improvements (page 20). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5).
In relation to the administering of claim 2, NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide (page 10 section ‘Arms and Interventions’).
Claim 2 recites ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines). MPEP 2111.02 recognizes that statements reciting the purpose or intended use must be evaluated to determine whether or not the purpose or intended use result in a manipulative difference. In the instant case, the recitation ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines) do not result in a manipulative difference. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for such intended use and purpose.
In relation to the subjects of claims 2 and 17-18, NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’). Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). NCT03891875 recognizes exclusion of exudative AMD (page 13) thus teaching no-exudative AMD. Applicants own specification recognizes GA involves irreversible loss of visual function (section 0003).
In relation to the time frame of claim 2 and 20, Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years.
Claim 3 refers to the area or changes of tEZa. Such claim is referring back to the intended uses as recited in claim 2 (i.e. ‘to reduce the rate’ as recited in the last 4 lines). As currently claimed, the required active method step is ‘administering’. Whether or not the intent or purpose is to reduce the rate in a particular way does not change the fact that the intended use or purpose does not require a manipulative difference (see MPEP 2111.02 II). Stated another way, independent of how the intended reduction is intended to be assessed, the active step as currently claimed remains administering. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for the claimed intended use and purpose. Further, NCT03891875 expressly recites measurements using optical coherence tomography (page 11 section ‘primary outcome measures’). In addition, Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20).
In relation to claim 21, Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1).
In relation to claim 24, Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
In relation to claim 25, Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph).
Claims 2-3, 17-18, 20-21 and 24-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,188,692 (692) in view of Reclaim 2 Data Slides (retrieved from https://stealthbt.com/wp-content/uploads/ClinTrial@Summit_Heier_ReCLAIM-2-presentation-final.5.21.pdf on 7/5/24, 20 pages; ‘Reclaim2’) in view of Clinical Trails (Clinical Trails entry for NCT03891875, retrieved from https://clinicaltrials.gov/study/NCT03891875?tab=history&a=25#version-content-panel on 7/5/24, 21 pages; ‘NCT03891875’) in view of Gorusupudi et al. (‘The age-related eye disease 2 study: micronutrients in the treatment of macular degeneration’ Adv Nutr v8 2017 pages 40-53; ‘Gorusupudi’) in view of Kaiser et al. (‘Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations’ Rheumatol Int v32 2012 pages 295-299; ‘Kaiser’).
692 recites a method for treating macular degeneration comprising administering a specific peptide (claims 1-2). 692 recites details about the subject (claim 4) and administration (claim 5) as well as additional agents (claims 7-9).
692 does not recite all of the specific details of the instant claims such as the specific amount administered.
The Wayback machine entry for Reclaim 2 Data slides (retrieved from https://web.archive.org/web/20220614080035/https://stealthbt.com/presentations/ on 7/9/24, 2 pages) reveals that the ReCLAIM-2 document was available on-line as of June 14 2022 (page 1).
Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20). Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12). Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17).
NCT03891875 teach a study to evaluate elamipretide in subjects with AMD with non-central GA (page 6 section ‘brief title’). As set forth on page 1 of the document, various versions of the study are available. As set forth on page 6 of the document, the version provided corresponds to the version dated May 25 2022 (version 25). NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide for 48 weeks (page 10 section ‘Arms and Interventions’). NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’) and recognizes exclusion of exudative AMD (page 13).
Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1). Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract). Gorusupudi teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1).
Kaiser teach that injection site reactions is a common adverse event associated with different kinds of biologics (page 295 last paragraph). Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that
diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph). Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 692 because 692 teach methods of treating macular degeneration with a specific peptide (which is elamipretide see section 0036 of the instant specification) so one would have been motivated to use known methods for known patients (details provided in NCT03891875) along with known agents (AREDS2 as taught by Gorusupudi, compare MPEP 2144.06) for treating macular degeneration. Further, since Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12) one would have been motivated to use the known agents and techniques taught by Kaiser. With respect to the length of administration, Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years. One would have had a reasonable expectation of success because 662 expressly teach for treating ARMD (claim 1) and Reclaim2 teach elamipretide mediated reduction of progressive EZ attenuation correlates with visual function improvements (page 20). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5).
In relation to the administering of claim 2, NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide (page 10 section ‘Arms and Interventions’).
Claim 2 recites ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines). MPEP 2111.02 recognizes that statements reciting the purpose or intended use must be evaluated to determine whether or not the purpose or intended use result in a manipulative difference. In the instant case, the recitation ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines) do not result in a manipulative difference. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for such intended use and purpose.
In relation to the subjects of claims 2 and 17-18, NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’). Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). NCT03891875 recognizes exclusion of exudative AMD (page 13) thus teaching no-exudative AMD. Applicants own specification recognizes GA involves irreversible loss of visual function (section 0003).
In relation to the time frame of claim 2 and 20, Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years.
Claim 3 refers to the area or changes of tEZa. Such claim is referring back to the intended uses as recited in claim 2 (i.e. ‘to reduce the rate’ as recited in the last 4 lines). As currently claimed, the required active method step is ‘administering’. Whether or not the intent or purpose is to reduce the rate in a particular way does not change the fact that the intended use or purpose does not require a manipulative difference (see MPEP 2111.02 II). Stated another way, independent of how the intended reduction is intended to be assessed, the active step as currently claimed remains administering. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for the claimed intended use and purpose. Further, NCT03891875 expressly recites measurements using optical coherence tomography (page 11 section ‘primary outcome measures’). In addition, Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20).
In relation to claim 21, Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1).
In relation to claim 24, Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
In relation to claim 25, Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph).
Claims 2-3, 17-18, 20-21 and 24-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 8,470,784 (784) in view of Reclaim 2 Data Slides (retrieved from https://stealthbt.com/wp-content/uploads/ClinTrial@Summit_Heier_ReCLAIM-2-presentation-final.5.21.pdf on 7/5/24, 20 pages; ‘Reclaim2’) in view of Clinical Trails (Clinical Trails entry for NCT03891875, retrieved from https://clinicaltrials.gov/study/NCT03891875?tab=history&a=25#version-content-panel on 7/5/24, 21 pages; ‘NCT03891875’) in view of Gorusupudi et al. (‘The age-related eye disease 2 study: micronutrients in the treatment of macular degeneration’ Adv Nutr v8 2017 pages 40-53; ‘Gorusupudi’) in view of Kaiser et al. (‘Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations’ Rheumatol Int v32 2012 pages 295-299; ‘Kaiser’).
784 recites a method for treating an ophthalmic condition comprising administering a specific peptide (claims 1-2). 784 recites details about the subject (claim 5) and administration (claim 6).
784 does not recite all of the specific details of the instant claims such as the specific amount administered.
The Wayback machine entry for Reclaim 2 Data slides (retrieved from https://web.archive.org/web/20220614080035/https://stealthbt.com/presentations/ on 7/9/24, 2 pages) reveals that the ReCLAIM-2 document was available on-line as of June 14 2022 (page 1).
Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20). Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12). Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17).
NCT03891875 teach a study to evaluate elamipretide in subjects with AMD with non-central GA (page 6 section ‘brief title’). As set forth on page 1 of the document, various versions of the study are available. As set forth on page 6 of the document, the version provided corresponds to the version dated May 25 2022 (version 25). NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide for 48 weeks (page 10 section ‘Arms and Interventions’). NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’) and recognizes exclusion of exudative AMD (page 13).
Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1). Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract). Gorusupudi teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1).
Kaiser teach that injection site reactions is a common adverse event associated with different kinds of biologics (page 295 last paragraph). Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that
diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph). Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 784 because 784 teach methods of treating macular degeneration with a specific peptide (which is elamipretide see section 0036 of the instant specification) so one would have been motivated to use known methods for known patients (details provided in NCT03891875) along with known agents (AREDS2 as taught by Gorusupudi, compare MPEP 2144.06) for treating macular degeneration. Further, since Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12) one would have been motivated to use the known agents and techniques taught by Kaiser. With respect to the length of administration, Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years. One would have had a reasonable expectation of success because 662 expressly teach for treating ARMD (claim 1) and Reclaim2 teach elamipretide mediated reduction of progressive EZ attenuation correlates with visual function improvements (page 20). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5).
In relation to the administering of claim 2, NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide (page 10 section ‘Arms and Interventions’).
Claim 2 recites ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines). MPEP 2111.02 recognizes that statements reciting the purpose or intended use must be evaluated to determine whether or not the purpose or intended use result in a manipulative difference. In the instant case, the recitation ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines) do not result in a manipulative difference. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for such intended use and purpose.
In relation to the subjects of claims 2 and 17-18, NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’). Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). NCT03891875 recognizes exclusion of exudative AMD (page 13) thus teaching no-exudative AMD. Applicants own specification recognizes GA involves irreversible loss of visual function (section 0003).
In relation to the time frame of claim 2 and 20, Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years.
Claim 3 refers to the area or changes of tEZa. Such claim is referring back to the intended uses as recited in claim 2 (i.e. ‘to reduce the rate’ as recited in the last 4 lines). As currently claimed, the required active method step is ‘administering’. Whether or not the intent or purpose is to reduce the rate in a particular way does not change the fact that the intended use or purpose does not require a manipulative difference (see MPEP 2111.02 II). Stated another way, independent of how the intended reduction is intended to be assessed, the active step as currently claimed remains administering. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for the claimed intended use and purpose. Further, NCT03891875 expressly recites measurements using optical coherence tomography (page 11 section ‘primary outcome measures’). In addition, Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20).
In relation to claim 21, Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1).
In relation to claim 24, Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
In relation to claim 25, Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph).
Claims 2-3, 17 and 20-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 34, 58, 82, 101 and 120-138 of copending Application No. 18/963,148 (reference application; ‘148’). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
148 teach treating AMD with elamipretide (claim 1). 148 recites treatment for 48 months (claim 121). 148 recites administering subcutaneously once daily at 40 mg/dose (claim 123). 148 recites dry AMD and geographic atrophy (claims 124-125). 148 recites administration of AREDS (claim 129).
In relation to the administering of claim 2, 148 teach treating AMD with elamipretide (claim 1) specifically administering subcutaneously once daily at 40 mg/dose (claim 123).
Claim 2 recites ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines). MPEP 2111.02 recognizes that statements reciting the purpose or intended use must be evaluated to determine whether or not the purpose or intended use result in a manipulative difference. In the instant case, the recitation ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines) do not result in a manipulative difference. Since 148 teach the same agent at the same dose for the elected patient population it would be suitable for such intended use and purpose.
In relation to the subjects of claims 2 and 17, 148 recites dry AMD and geographic atrophy (claims 124-125).
In relation to the time frame of claim 2 and 20, 148 recites treatment for 48 months (claim 121).
Claim 3 refers to the area or changes of tEZa. Such claim is referring back to the intended uses as recited in claim 2 (i.e. ‘to reduce the rate’ as recited in the last 4 lines). As currently claimed, the required active method step is ‘administering’. Whether or not the intent or purpose is to reduce the rate in a particular way does not change the fact that the intended use or purpose does not require a manipulative difference (see MPEP 2111.02 II). Stated another way, independent of how the intended reduction is intended to be assessed, the active step as currently claimed remains administering. Since 148 teach the same agent at the same dose for the elected patient population it would be suitable for the claimed intended use and purpose.
In relation to claim 21, 148 recites administration of AREDS (claim 129).
Claims 2-3, 17-18, 20-21 and 24-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 34, 58, 82, 101 and 120-138 of copending Application No. 18963148 in view of Reclaim 2 Data Slides (retrieved from https://stealthbt.com/wp-content/uploads/ClinTrial@Summit_Heier_ReCLAIM-2-presentation-final.5.21.pdf on 7/5/24, 20 pages; ‘Reclaim2’) in view of Clinical Trails (Clinical Trails entry for NCT03891875, retrieved from https://clinicaltrials.gov/study/NCT03891875?tab=history&a=25#version-content-panel on 7/5/24, 21 pages; ‘NCT03891875’) in view of Gorusupudi et al. (‘The age-related eye disease 2 study: micronutrients in the treatment of macular degeneration’ Adv Nutr v8 2017 pages 40-53; ‘Gorusupudi’) in view of Kaiser et al. (‘Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations’ Rheumatol Int v32 2012 pages 295-299; ‘Kaiser’).
This is a provisional nonstatutory double patenting rejection.
148 teach treating AMD with elamipretide (claim 1). 148 recites treatment for 48 months (claim 121). 148 recites administering subcutaneously once daily at 40 mg/dose (claim 123). 148 recites dry AMD and geographic atrophy (claims 124-125). 148 recites administration of AREDS (claim 129).
148 makes no mention of an injection site as in claims 24-25 or non-central GA as in claim 18.
The Wayback machine entry for Reclaim 2 Data slides (retrieved from https://web.archive.org/web/20220614080035/https://stealthbt.com/presentations/ on 7/9/24, 2 pages) reveals that the ReCLAIM-2 document was available on-line as of June 14 2022 (page 1).
Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20). Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12). Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17).
NCT03891875 teach a study to evaluate elamipretide in subjects with AMD with non-central GA (page 6 section ‘brief title’). As set forth on page 1 of the document, various versions of the study are available. As set forth on page 6 of the document, the version provided corresponds to the version dated May 25 2022 (version 25). NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide for 48 weeks (page 10 section ‘Arms and Interventions’). NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’) and recognizes exclusion of exudative AMD (page 13).
Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1). Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract). Gorusupudi teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1).
Kaiser teach that injection site reactions is a common adverse event associated with different kinds of biologics (page 295 last paragraph). Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that
diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph). Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 148 because 148 teach methods of treating macular degeneration with elamipretide so one would have been motivated to use known methods for known patients (details provided in NCT03891875) along with known agents (AREDS2 as taught by Gorusupudi, compare MPEP 2144.06) for treating macular degeneration. Further, since Reclaim2 teach injection site adverse events in about 60% of subjects (pages 11-12) one would have been motivated to use the known agents and techniques taught by Kaiser. With respect to the length of administration, Reclaim2 teach that progressive mitochondrial function contributes to AMD and show results over the time frame of 50 years (slide 4). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5). Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years. One would have had a reasonable expectation of success because 662 expressly teach for treating ARMD (claim 1) and Reclaim2 teach elamipretide mediated reduction of progressive EZ attenuation correlates with visual function improvements (page 20). Reclaim2 teach elamipretide improves inner mitochondrial membrane stability, enhances ATP synthesis and reduces pathogenic reactive oxygen species (slide 5).
In relation to the administering of claim 2, NCT03891875 teach daily 40 mg subcutaneous injection of elamipretide (page 10 section ‘Arms and Interventions’).
Claim 2 recites ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines). MPEP 2111.02 recognizes that statements reciting the purpose or intended use must be evaluated to determine whether or not the purpose or intended use result in a manipulative difference. In the instant case, the recitation ‘of reducing..’ (line 1) as well as ‘to reduce..’ (last 4 lines) do not result in a manipulative difference. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for such intended use and purpose.
In relation to the subjects of claims 2 and 17-18, NCT03891875 teach inclusion criteria of AMD with non-central GA (page 12 section ‘Criteria’). Reclaim2 teach that elamipretide protects mitochondria in a diabetic mouse model (page 5) and a proof of concept study in dry age-related macular degeneration and noncentral GA was conducted (page 8). NCT03891875 recognizes exclusion of exudative AMD (page 13) thus teaching no-exudative AMD. Applicants own specification recognizes GA involves irreversible loss of visual function (section 0003).
In relation to the time frame of claim 2 and 20, Reclaim2 shows that elamipretide caused a reduction in attenuation that appeared to increase over time for 48 weeks (slide 16). Reclaim2 states that the evidence shows that slowing EZ attenuation has a positive effect on visual function (slide 17). Based on the beneficial effects of administration one would have been motivated to continue administration past 48 weeks. Further, Gorusupudi teach that age-related macular degeneration is one of the leading causes of vision loss in the elderly (abstract) and teach that studies of the relation between nutrients and AMD includes studies that were conducted for 2 years (first entry of table 1), 8 years (5th entry of table 1), 12.5 years (7th entry of table 1), 6.3 years (9th entry of table 1) and 10 years (10th entry of table 1). Thus, one would have been motivated to continue administration on the time frame of years.
Claim 3 refers to the area or changes of tEZa. Such claim is referring back to the intended uses as recited in claim 2 (i.e. ‘to reduce the rate’ as recited in the last 4 lines). As currently claimed, the required active method step is ‘administering’. Whether or not the intent or purpose is to reduce the rate in a particular way does not change the fact that the intended use or purpose does not require a manipulative difference (see MPEP 2111.02 II). Stated another way, independent of how the intended reduction is intended to be assessed, the active step as currently claimed remains administering. Since NCT03891875 teach the same agent at the same dose for the elected patient population it would be suitable for the claimed intended use and purpose. Further, NCT03891875 expressly recites measurements using optical coherence tomography (page 11 section ‘primary outcome measures’). In addition, Reclaim2 sets forth the trial design which refers to ellipsoid zone attenuation (page 9 compare figure 1 of the instant specification). Reclaim2 teach a mixed-effects model for repeated measures to analyze the data (page 13). Reclaim2 teach elamipretide reduced attenuation of the mitochondria-rich EZ (pages 16-20).
In relation to claim 21, Gorusupudi teach that AREDS2 formulation is the standard of care for reducing the probability of advanced AMD and there is evidence that subjects receiving AREDS2 type supplements could have stabilization and improvement of best corrected visual acuity (page 49 last paragraph of section 1).
In relation to claim 24, Kaiser teach the use of a cool pack before and after injection (page 297 last complete paragraph). Kaiser teach alternating injection sites (page 298 first paragraph).
In relation to claim 25, Kaiser teach the use of antihistamines to treat injection site reactions (page 297 2nd column 1st complete paragraph, last complete paragraph on page 297, 1st and 2nd paragraph in second column on page 298). Kaiser teach that diphenhydramine is a known anti-histamine (page 296 2nd column 1st paragraph, page 298 2nd column 2nd paragraph).
Response to Arguments – double patenting
Applicant's arguments filed 2/26/26 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants request that the rejections be held in abeyance, nothing has been done to overcome the rejections so they remain of record.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658