DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a national stage entry of PCT/US21/62850 filed on 12/10/2021 which claims priority to U.S. Provisional Application No. 63/124,695 filed on 12/11/2020.
Response to Amendment
Applicant’s amendment filed on June 4, 2026 amending claims 1, 13, and 16; cancelling claims 2 and 11; and adding new claim 26 has been entered. Claims 17-25 were previously canceled. Claims 1, 3-10, 12-16 and 26 are currently pending.
Election/Restrictions
Applicant's election with traverse of
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as a species of a compound of Formula I in the reply filed on June 4, 2026 is acknowledged. The traversal is on the grounds that the search for each of the claims of Groups 1 and 2 will substantially overlap. Applicant argues that the scope of the claims of Group 1 are such that additional searching would not be required to adequately search the subject matter of Group 2 since the claims of Group 1 and Group 2 are directed to methods of using compounds that share a common structure for the same purpose. Thus Applicant argues that search and examination can be concurrently performed, and the Examiner will not be seriously burdened by searching and considering the inventions as described in all the presently filed claims.
This is not found persuasive because this application is a national stage entry of PCT/US21/62850 and as such the basis of restriction/election requirement is unity of invention. In the instant case, the technical feature is not considered a special technical feature because as detailed on page 6 of the prior action, unity of invention is lacking because even though the inventions require the technical feature of a compound of formula I or IA for treating dry age-related macular degeneration (dry AMD), this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Rishton et al. WO 2015/116923 A1 which teaches the same compounds of Formula I which are used in methods of treating a proteopathic disease associated with Abeta oligomer toxicity, such as a CNS proteopathy, characterized by an increase in Abeta protein, such as macular degeneration [0218]-[0219]. Moreover, even though the compounds of Formula I and IA share a common structure, the common structure is not a significant structural element because it represents only a small portion of the compound structures and does not constitute a structurally distinctive portion in view of Rishton et al. WO 2015/116923 A1 which discloses the same compounds of Formula I [008]. In addition, because the common structure between Formula I and IA, which is merely a substituted or unsubstituted phenyl ring is not a significant structural element, the search for Formula I would not necessarily reveal Formula IA. Likewise, a search for Formula IA would not necessarily reveal Formula I. Thus multiple non-overlapping searches would be required in searching all compounds as previously claimed. Thus a search burden exists in searching all compounds as previously claimed.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-10 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.
Newly submitted claim 26 is directed to an invention that lacks unity with the invention originally claimed for the following reasons: New claim 26 is drawn to a method of preventing cell death in retinal pigment epithelial cells, in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of the Formula I which is
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or a pharmaceutically acceptable salt thereof, thereby preventing cell death in retinal pigment epithelial cells; while the original invention is directed to a method of treating dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound selected from the group consisting of: a compound of Formula I or IA thereby treating the dry age-related macular degeneration.
Unity of invention is lacking because even though the inventions require the technical feature of a compound of formula I which is
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, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Rishton et al. WO 2015/116923 A1 which teaches the same compounds of Formula I including
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.
Accordingly, claim 26 is withdrawn from consideration as being directed to a nonelected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 1, 3-6, and 12-16 are currently being examined as they read on the elected species.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 1, 3-6 and 12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 of the instant application claims a method of treating geographic atrophy dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound selected from the group consisting of: A. a compound of Formula I thereby treating the geographic atrophy dry age-related macular degeneration. The claim is indefinite since the claim recites “a compound selected from the group consisting of”, however, there is only one group of compounds listed since the claim has been amended to delete compounds of Formula IA. Thus it is unclear why the claim still recites “a compound selected from the group consisting of” when there is only one group of compounds claimed. Thus claim 1 and all claims dependent upon claim 1 (claims 3-6 and 12) are rejected.
A suggestion to overcome this rejection is to amend claim 1 as follows: A method of treating geographic atrophy dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I.
Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 12 of the instant application claims a method of treating dry age-related macular degeneration comprising administering to a subject in need thereof, a therapeutically effective amount of a pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient. However, claim 1 of the instant application is not drawn solely to a compound, rather claim 1 claims a method of treating geographic atrophy dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound selected from the group consisting of: A. a compound of Formula I thereby treating the geographic atrophy dry age-related macular degeneration. Claim 12 does not recite treating geographic atrophy dry age-related macular degeneration as claimed in claim 1 and furthermore claim 12 claims administering a composition which is not recited in claim 1. Thus claim 12 is rejected for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-6, and 12-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9,796,672 B2 (Provided on IDS dated 03/19/2024) in view of Burbidge et al. WO 2009/040336 A1.
Claims 1, 3-6, and 12-16 of the instant application claim a method of treating geographic atrophy dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I such as
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thereby treating the geographic atrophy dry age-related macular degeneration.
Claims 1-15 of ‘672 claim a compound of Formula
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or a pharmaceutically acceptable salt thereof such as the fumarate salt and a composition thereof as well as a method for inhibiting amyloid beta effect on a neuronal cell comprising administering to a subject in need thereof an effective amount of said compound and treating Alzheimer’s disease.
‘672 does not claim treating geographic atrophy dry age-related macular degeneration (dry AMD) or dry AMD.
Burbidge et al. teaches treating diseases or disorders affecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits, particularly age related macular degeneration (abstract and page 1 lines 4-10). Burbidge et al. teaches that age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and there are two major clinical presentations of AMD, including atrophic (dry) AMD which is characterized by the degeneration of retinal pigment epithelial (RPE) and neuroretina and wet AMD characterized by choroidal neovascularization (page 1 line 38-page 2 line 8). The early stages of atrophic AMD are associated with the formation of drusen, under the RPE cell layer, and early atrophic AMD can progress to an end stage disease where the RPE degenerates completely and forms sharply demarcated areas of RPE atrophy in the region of the macula: "geographic atrophy" (page 1 lines 41-44). In this form of the disease, the degeneration of RPE results in the secondary death of macular rods and cones and in these cases this leads to the severe age-related vision loss (page 1 line 44-page 2 line 2).
Burbidge et al. further teaches that there are considerable similarities between the formation of drusen in AMD and in the formation of plaques in Alzheimer's disease (AD) (page 2 lines 22-23). Drusen have been found from histopathological and proteomic studies to contain similar types of protein components to AD plaques, including the presence of apolipoprotein E and β-amyloid, (Aβ), suggesting some sharing of the pathways of AD plaque and AMD drusen formations (page 2 lines 22-27). The Aβ found in drusen is thought to be locally derived from the RPE cells. Burbidge further teaches the involvement of the ageing process and also secondary inflammatory arrest also appears to be linked in both AMD and AD, wherein in the inflammatory process associated with AMD there is an associated rise in expression of acute-proteins such as C-reactive protein (CRP) and Aβ protein which induce complement activation and the activation of pro-inflammatory cytokines (page 2 lines 27-34). Thus, Burbidge et al. teaches that the evidence supports β-amyloid as a key factor in AMD pathology and disease and that the evidence implies that clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ may provide a possible route to clearing drusen in AMD, reducing complement activation in AMD, reducing RPE atrophy and potentially reducing the induction of VEGF expression in RPE and its localization at high levels around drusen (page 6 lines 18-30). Burbidge et al. teaches that such therapy could therefore provide means of preventing, delaying, attenuating or reversing the loss of vision due to AMD and its progression to geographic atrophy and/or exudative AMD by decreasing levels of Aβ containing drusen and/or local Aβ in the surrounding environment of the RPE and thereby interfering in both the early and later stages of AMD and treating the underlying cellular decline that causes the loss of vision (page 6 lines 18-30).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of ‘672 which claims a method for inhibiting amyloid beta effect on a neuronal cell comprising administering to a subject in need thereof an effective amount of
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or a composition containing said compound and treating Alzheimer’s disease, with the teachings of Burbidge et al. which teaches that similar to Alzheimer’s disease, age related macular degeneration is a disease or disorder affecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits wherein evidence supports β-amyloid as a key factor in AMD pathology and disease and wherein evidence supports that by clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ may provide a possible route to clearing drusen in AMD, reducing complement activation in AMD, reducing RPE atrophy and potentially reducing the induction of VEGF expression in RPE and its localization at high levels around drusen leading to preventing, delaying, attenuating or reversing the loss of vision due to AMD and its progression to geographic atrophy and/or exudative AMD.
Thus since AMD and its progression to geographic atrophy is associated with β-amyloid deposits and since evidence supports the clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ for the treatment of AMD, an ordinary skilled artisan would have been motivated to treat AMD including geographic atrophy AMD according to the methods of ‘672 with a reasonable expectation of success. Thus the cited claims of the instant application are rendered obvious the cited claims of ‘672.
Claims 1, 3-6, and 12-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,207,991 B2 (Provided on IDS dated 03/19/2024) in view of Burbidge et al. WO 2009/040336 A1.
Claims 1, 3-6, and 12-16 of the instant application claim a method of treating geographic atrophy dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I such as
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thereby treating the geographic atrophy dry age-related macular degeneration.
Claims 1-15 of ‘991 claim a compound of Formula I such as
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or a pharmaceutically acceptable salt thereof and a composition thereof as well as a method for inhibiting amyloid beta effect on a neuronal cell comprising administering to a subject in need thereof an effective amount of said compound and treating Alzheimer’s disease.
‘991 does not claim treating geographic atrophy dry age-related macular degeneration (dry AMD) or dry AMD.
Burbidge et al. teaches treating diseases or disorders affecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits, particularly age related macular degeneration (abstract and page 1 lines 4-10). Burbidge et al. teaches that age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and there are two major clinical presentations of AMD, including atrophic (dry) AMD which is characterized by the degeneration of retinal pigment epithelial (RPE) and neuroretina and wet AMD characterized by choroidal neovascularization (page 1 line 38-page 2 line 8). The early stages of atrophic AMD are associated with the formation of drusen, under the RPE cell layer, and early atrophic AMD can progress to an end stage disease where the RPE degenerates completely and forms sharply demarcated areas of RPE atrophy in the region of the macula: "geographic atrophy" (page 1 lines 41-44). In this form of the disease, the degeneration of RPE results in the secondary death of macular rods and cones and in these cases this leads to the severe age-related vision loss (page 1 line 44-page 2 line 2).
Burbidge et al. further teaches that there are considerable similarities between the formation of drusen in AMD and in the formation of plaques in Alzheimer's disease (AD) (page 2 lines 22-23). Drusen have been found from histopathological and proteomic studies to contain similar types of protein components to AD plaques, including the presence of apolipoprotein E and β-amyloid, (Aβ), suggesting some sharing of the pathways of AD plaque and AMD drusen formations (page 2 lines 22-27). The Aβ found in drusen is thought to be locally derived from the RPE cells. Burbidge further teaches the involvement of the ageing process and also secondary inflammatory arrest also appears to be linked in both AMD and AD, wherein in the inflammatory process associated with AMD there is an associated rise in expression of acute-proteins such as C-reactive protein (CRP) and Aβ protein which induce complement activation and the activation of pro-inflammatory cytokines (page 2 lines 27-34). Thus, Burbidge et al. teaches that the evidence supports β-amyloid as a key factor in AMD pathology and disease and that the evidence implies that clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ may provide a possible route to clearing drusen in AMD, reducing complement activation in AMD, reducing RPE atrophy and potentially reducing the induction of VEGF expression in RPE and its localization at high levels around drusen (page 6 lines 18-30). Burbidge et al. teaches that such therapy could therefore provide means of preventing, delaying, attenuating or reversing the loss of vision due to AMD and its progression to geographic atrophy and/or exudative AMD by decreasing levels of Aβ containing drusen and/or local Aβ in the surrounding environment of the RPE and thereby interfering in both the early and later stages of AMD and treating the underlying cellular decline that causes the loss of vision (page 6 lines 18-30).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of ‘991 which claims a method for inhibiting amyloid beta effect on a neuronal cell comprising administering to a subject in need thereof an effective amount of
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or a composition containing said compound and treating Alzheimer’s disease, with the teachings of Burbidge et al. which teaches that similar to Alzheimer’s disease, age related macular degeneration is a disease or disorder affecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits wherein evidence supports β-amyloid as a key factor in AMD pathology and disease and wherein evidence supports that by clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ may provide a possible route to clearing drusen in AMD, reducing complement activation in AMD, reducing RPE atrophy and potentially reducing the induction of VEGF expression in RPE and its localization at high levels around drusen leading to preventing, delaying, attenuating or reversing the loss of vision due to AMD and its progression to geographic atrophy and/or exudative AMD.
Thus since AMD and its progression to geographic atrophy is associated with β-amyloid deposits and since evidence supports the clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ for the treatment of AMD, an ordinary skilled artisan would have been motivated to treat AMD including geographic atrophy AMD according to the methods of ‘991 with a reasonable expectation of success. Thus the cited claims of the instant application are rendered obvious the cited claims of ‘991.
Claims 1, 3-6, and 12-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,466,795 (Provided on IDS dated 06/04/2026).
Claims 1, 3-6, and 12-16 of the instant application claim a method of treating geographic atrophy dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I such as
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or a therapeutically acceptable salt thereof of a composition thereof, thereby treating the geographic atrophy dry age-related macular degeneration.
The claims of ‘795 claims a pharmaceutical composition comprising a compound of the Formula
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or a therapeutically acceptable salt thereof such as the fumarate salt.
Although the use as claimed in the instant claims is not claimed in ‘795, since ‘795 claims the same compound, the use as claimed in the instant claims is inherent to the composition of ‘795. Moreover, this rejection is being made since no restriction between product and process of use was required, and thus the product and process of using the product are not patentably distinct.
Claims 1, 3-6, and 12-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-10, 12-13, 54-59, 61 and 63-66 of U.S. Application No. 17/798,667 (U.S. Publication No. 2023/0098944 A1) in view of Burbidge et al. WO 2009/040336 A1.
Claims 1, 3-6, and 12-16 of the instant application claim a method of treating geographic atrophy dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I such as
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thereby treating the geographic atrophy dry age-related macular degeneration.
The cited claims of copending ‘667 claim a method of reducing amyloid b monomer levels in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula:
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or a pharmaceutically acceptable salt thereof and a composition thereof, as well as treating Alzheimer’s disease comprising administering to a subject said compound or composition thereof.
Copending ‘667 does not claim treating geographic atrophy dry age-related macular degeneration (dry AMD) or dry AMD.
Burbidge et al. teaches treating diseases or disorders affecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits, particularly age related macular degeneration (abstract and page 1 lines 4-10). Burbidge et al. teaches that age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and there are two major clinical presentations of AMD, including atrophic (dry) AMD which is characterized by the degeneration of retinal pigment epithelial (RPE) and neuroretina and wet AMD characterized by choroidal neovascularization (page 1 line 38-page 2 line 8). The early stages of atrophic AMD are associated with the formation of drusen, under the RPE cell layer, and early atrophic AMD can progress to an end stage disease where the RPE degenerates completely and forms sharply demarcated areas of RPE atrophy in the region of the macula: "geographic atrophy" (page 1 lines 41-44). In this form of the disease, the degeneration of RPE results in the secondary death of macular rods and cones and in these cases this leads to the severe age-related vision loss (page 1 line 44-page 2 line 2).
Burbidge et al. further teaches that there are considerable similarities between the formation of drusen in AMD and in the formation of plaques in Alzheimer's disease (AD) (page 2 lines 22-23). Drusen have been found from histopathological and proteomic studies to contain similar types of protein components to AD plaques, including the presence of apolipoprotein E and β-amyloid, (Aβ), suggesting some sharing of the pathways of AD plaque and AMD drusen formations (page 2 lines 22-27). The Aβ found in drusen is thought to be locally derived from the RPE cells. Burbidge further teaches the involvement of the ageing process and also secondary inflammatory arrest also appears to be linked in both AMD and AD, wherein in the inflammatory process associated with AMD there is an associated rise in expression of acute-proteins such as C-reactive protein (CRP) and Aβ protein which induce complement activation and the activation of pro-inflammatory cytokines (page 2 lines 27-34). Thus, Burbidge et al. teaches that the evidence supports β-amyloid as a key factor in AMD pathology and disease and that the evidence implies that clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ may provide a possible route to clearing drusen in AMD, reducing complement activation in AMD, reducing RPE atrophy and potentially reducing the induction of VEGF expression in RPE and its localization at high levels around drusen (page 6 lines 18-30). Burbidge et al. teaches that such therapy could therefore provide means of preventing, delaying, attenuating or reversing the loss of vision due to AMD and its progression to geographic atrophy and/or exudative AMD by decreasing levels of Aβ containing drusen and/or local Aβ in the surrounding environment of the RPE and thereby interfering in both the early and later stages of AMD and treating the underlying cellular decline that causes the loss of vision (page 6 lines 18-30).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of Copending ‘667 which claims a method of reducing amyloid b monomer levels and a method for treating Alzheimer’s disease comprising administering to a subject in need thereof an effective amount of
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or a pharmaceutically acceptable salt thereof or a composition containing said compound or salt thereof, with the teachings of Burbidge et al. which teaches that similar to Alzheimer’s disease, age related macular degeneration is a disease or disorder affecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits wherein evidence supports β-amyloid as a key factor in AMD pathology and disease and wherein evidence supports that by clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ may provide a possible route to clearing drusen in AMD, reducing complement activation in AMD, reducing RPE atrophy and potentially reducing the induction of VEGF expression in RPE and its localization at high levels around drusen leading to preventing, delaying, attenuating or reversing the loss of vision due to AMD and its progression to geographic atrophy and/or exudative AMD.
Thus since AMD and its progression to geographic atrophy is associated with β-amyloid deposits and since evidence supports the clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ for the treatment of AMD, an ordinary skilled artisan would have been motivated to treat AMD including geographic atrophy AMD according to the methods of copending ‘667 with a reasonable expectation of success. Thus the cited claims of the instant application are rendered obvious the cited claims of copending ‘667.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-6, and 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Rishton et al. U.S. Patent No. 9,796,672 B2 (Provided on IDS) in view of Burbidge et al. WO 2009/040336 A1.
Claims 1, 3-6, and 12-16 of the instant application claim a method of treating geographic atrophy dry age-related macular degeneration (dry AMD), comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I such as
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thereby treating the geographic atrophy dry age-related macular degeneration.
Rishton et al. teaches isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology (abstract).
Rishton et al. teaches the same compounds of formula I as claimed in the instant claims (column 2 line 25-column 4 line 50). Rishton et al. specifically teaches Applicant’s elected species (column 23 line 20).
Rishton et al. further teaches methods of treating a proteopathic disease associated with Abeta oligomer toxicity comprising contacting a subject with such a proteopathic disease with a sigma-2 antagonist disclosed therein or a composition containing the same that binds the sigma-2 receptor (column 102 lines 36-46). Rishton et al. teaches in some embodiments, the proteopathic disease is a CNS proteopathy, characterized by an increase in Abeta protein, such as MCI, Down's Syndrome, macular degeneration or Alzheimer's disease, and the like (column 102 lines 36-46).
Claims 1-3 and 7-14 of Rishton et al. claim a compound of Formula
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or a pharmaceutically acceptable salt thereof such as the fumarate salt and composition thereof as well as a method for inhibiting amyloid beta effect on a neuronal cell comprising administering to a subject in need thereof an effective amount of said compound.
Rishton et al. does not specifically exemplify treating geographic atrophy dry age-related macular degeneration (dry AMD) or dry AMD.
However, Rishton et al. specifically teaches treating a proteopathic disease such as a CNS proteopathy, characterized by an increase in Abeta protein, such as macular degeneration or Alzheimer's disease (column 102 lines 36-46). Thus a person of ordinary skill in the art would have been motivated to treat macular degeneration according to the teachings of Rishton et al. with a reasonable expectation of similar success as Alzheimer’s disease.
In addition, Burbidge et al. teaches treating diseases or disorders affecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits, particularly age related macular degeneration (abstract and page 1 lines 4-10). Burbidge et al. teaches that age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and there are two major clinical presentations of AMD, including atrophic (dry) AMD which is characterized by the degeneration of retinal pigment epithelial (RPE) and neuroretina and wet AMD characterized by choroidal neovascularization (page 1 line 38-page 2 line 8). The early stages of atrophic AMD are associated with the formation of drusen, under the RPE cell layer, and early atrophic AMD can progress to an end stage disease where the RPE degenerates completely and forms sharply demarcated areas of RPE atrophy in the region of the macula: "geographic atrophy" (page 1 lines 41-44). In this form of the disease, the degeneration of RPE results in the secondary death of macular rods and cones and in these cases this leads to the severe age-related vision loss (page 1 line 44-page 2 line 2).
Burbidge et al. further teaches that there are considerable similarities between the formation of drusen in AMD and in the formation of plaques in Alzheimer's disease (AD) (page 2 lines 22-23). Drusen have been found from histopathological and proteomic studies to contain similar types of protein components to AD plaques, including the presence of apolipoprotein E and β-amyloid, (Aβ), suggesting some sharing of the pathways of AD plaque and AMD drusen formations (page 2 lines 22-27). The Aβ found in drusen is thought to be locally derived from the RPE cells. Burbidge further teaches the involvement of the ageing process and also secondary inflammatory arrest also appears to be linked in both AMD and AD, wherein in the inflammatory process associated with AMD there is an associated rise in expression of acute-proteins such as C-reactive protein (CRP) and Aβ protein which induce complement activation and the activation of pro-inflammatory cytokines (page 2 lines 27-34). Thus, Burbidge et al. teaches that the evidence supports β-amyloid as a key factor in AMD pathology and disease and that the evidence implies that clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ may provide a possible route to clearing drusen in AMD, reducing complement activation in AMD, reducing RPE atrophy and potentially reducing the induction of VEGF expression in RPE and its localization at high levels around drusen (page 6 lines 18-30). Burbidge et al. teaches that such therapy could therefore provide means of preventing, delaying, attenuating or reversing the loss of vision due to AMD and its progression to geographic atrophy and/or exudative AMD by decreasing levels of Aβ containing drusen and/or local Aβ in the surrounding environment of the RPE and thereby interfering in both the early and later stages of AMD and treating the underlying cellular decline that causes the loss of vision (page 6 lines 18-30).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Rishton et al. which teaches methods of treating a proteopathic disease associated with Abeta oligomer toxicity comprising contacting a subject with such a proteopathic disease with a sigma-2 antagonist such as
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or a composition containing the same that binds the sigma-2 receptor, wherein the proteopathic disease is a CNS proteopathy, characterized by an increase in Abeta protein, such as macular degeneration or Alzheimer's disease, with the teachings of Burbidge et al. which teaches that age related macular degeneration is a disease or disorder affecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits wherein evidence supports β-amyloid as a key factor in AMD pathology and disease and wherein evidence supports that by clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ may provide a possible route to clearing drusen in AMD, reducing complement activation in AMD, reducing RPE atrophy and potentially reducing the induction of VEGF expression in RPE and its localization at high levels around drusen leading to preventing, delaying, attenuating or reversing the loss of vision due to AMD and its progression to geographic atrophy and/or exudative AMD.
Thus since AMD and its progression to geographic atrophy is associated with β-amyloid deposits and since evidence supports the clearing of Aβ by agents that bind and potentially neutralize or just remove Aβ for the treatment of AMD, an ordinary skilled artisan would have been motivated to treat AMD including geographic atrophy AMD according to the methods of Rishton et al. with a reasonable expectation of success. Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1, 3-6, and 12-16 are rejected. Claims 2, 11 and 17-25 are canceled. Claims 7-10 and 26 are withdrawn. No claims are allowed.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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