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
The instant application is a 371 National Stage Entry of PCT/KR2022/017991 filed on November 15, 2022 which claims priority to foreign application No. KR10-2022-0035142 filed on March 22, 2022.
No English Translation
Examiner notes that no certified translation of the Foreign Application KR10-2022-0035142 (filed March 22, 2022) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5-6, 9-10 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.
Claims 5-6, 9-10 recite the phrase, “the compound is used”, which is ambiguous, describing an intended use of a compound (“The compound…”) or composition (“…is used in a pharmaceutical composition” or “food composition”). Applicant is requested to clarify the claims. The Examiner suggests amending to “A composition comprising the compound of claim…” if the claims are drawn to compositions. For example:
Claim 5. A pharmaceutical composition for the treatment of macular degeneration comprising the
The above amendment would read as a composition with an intended use.
For the purposes of applying art, the claims are construed as compositions comprising the compound with intended use. The limitations are met by a composition comprising the compound, capable of performing the intended use.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-3, 5-7, 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021066608 A11 as evidenced by the machine translation2 in view of Wermuth3.
Claim interpretation: the intended use of claims 5-6, 9-10 is not given patentable weight in instant rejection.
Instant Formula 1-1C is understood to be CAS# 2991249-78-4 and formula 1-1D is understood to be CAS# 2991249-79-5.
Regarding claims 1-3, 7 and compounds of Formula 1-1D or 1-1C and increased expression of the klotho gene, WO’608 teaches compounds for inducing the expression of the klotho gene (see WO’608 at Abstract) such as Example 10 FCCS-19025, also known as CAS# 2327998-93-4 (see WO’608 at p. 32). WO’608 teaches Figure 5, it was confirmed that the expression levels of the klotho gene with CAS# 2327998-93-4 and Example 8 were higher than those in comparative Example 1, and CAS# 2327998-93-4 was about ten times more improved than the comparative Example 1 (see WO’608 at Figure 5 and WO'608T at Description p. 160 ¶[0427]).
WO’608 FCCS-19025
Example 10
CAS# 2327998-93-4
Instant Formula 1-1C
CAS# 2991249-78-4
Instant Formula 1-1D
CAS# 2991249-79-5
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Regarding claims 5-6, 9-10 and a composition, WO’608 teaches the compounds of the present invention may be administered as formulations (reading on instant compositions) and prepared using diluents or excipients (see WO'608T at p. 93 ¶[0246]). WO’608 also teaches the disclosed compounds may be used in pharmaceutical compositions, cosmetic compositions, or food compositions for preventing skin aging, inhibiting cell aging, or preventing, improving, or treating diseases caused by vascular aging or kidney disease (see WO'608T Description at p. 35 ¶[0085]).
The prior art differs from the instant claims as follows: While WO’608 teaches structurally similar compounds for increased expression of the klotho gene, i) CAS# 2327998-93-4 differs from the instant species by H vs F and ii) WO’608 does not specify the intended use of treating macular degeneration or protecting retinal pigment epithelial cells from oxidative stress.
However,
Regarding H vs F, WO’608 contemplates substitution at the R1 and R2 positions of Formula 1 (see WO’608 at p. 4). Wermuth teaches fluorine for hydrogen isosterism often improves compounds in regards to metabolic degeneration (see Wermuth at p. 227 "(b) Electronic aspects").
WO’608 Formula 1
WO’608 FCCS-19025
Example 10
CAS# 2327998-93-4
Instant Formula 1-1D
CAS# 2991249-79-5
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Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding H vs F, per MPEP § 2143(I)(B), a prima facie case of obviousness exists for simple substitution of one known element for another to obtain predictable results. It would have been obvious to an artisan to modify WO’608’s CAS# 2327998-93-4 to be substituted with fluorine in lieu of hydrogen with a reasonable expectation of success because the prior art contemplates substitution at the R1 and R2 positions (as taught by WO’608), and teaches the fluorine for hydrogen substitution can improve metabolic properties (as taught by Wermuth).
Regarding intended use, WO’608 teaches a pharmaceutical or food composition comprising CAS# 2327998-93-4. An artisan would appreciate the prior art compositions (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) are structurally similar to those instantly claimed (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) and are capable of being administered to a subject, and thus capable of performing the intended uses instantly claimed.
Furthermore, it is well-within the ordinary skill in art to incorporate fluorine in lieu of hydrogen.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 4-6, 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over WO’608 as evidenced by WO’608T in view of Wermuth as applied to claims 1-3, 5-7, 9-10 above and in further view of Kokkinaki et al.4
Claim interpretation: the intended use of claims 5-6, 9-10 is given patentable weight in instant rejection.
Recall WO’608 teaches food and pharmaceutical compositions comprising benzoxazoles for increasing expression of the klotho gene, and a method of administering to a subject.
The prior art differs from the instant claims as follows: While WO’608 teaches compositions comprising an obvious variant of compounds Formula 1-1D and Formula 1-1C, WO’608 does not specify the property of i) protecting the retinal pigment epithelial cells from oxidative stress or the method of ii) preventing or ameliorating macular degeneration.
However,
Regarding claims 4, 8 and protecting retinal pigment epithelial cells, Kokkinaki teaches morphological changes in the retinal pigment epithelium (RPE) have been associated with retinal degenerative disorders (see Kokkinaki at Abstract). Kokkinaki also teaches the klotho gene protects against oxidative stress (see Kokkinaki at Title).
Regarding claims 5-6, 9-12 and a method/use of treating macular degeneration, Kokkinaki teaches aging-induced decline in phagocytosis is thought to contribute to age-related macular degeneration (see Kokkinaki at p. 16350 left col. ¶6).
Regarding claims 4-6, 8-12 and the nexus to the klotho gene, Kokkinaki teaches the klotho gene has a regulatory role in RPE phagocytosis and shows downregulation of the klotho gene inhibits phagocytosis in RPE cells (see Kokkinaki at p. 16356 right col. ¶1).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. The prior art teaches a highly similar structural benzoxazole to the instantly claimed invention, with a similar utility as the instantly claimed invention (increasing expression of the klotho gene); accordingly, an artisan would readily appreciate CAS# 2327998-93-4 (and its obvious variants), known to increase klotho gene expression, could be utilized in the treatment of macular degeneration or protecting RPE against oxidative stress, because the prior art teaches a decline in klotho gene expression leads to RPE degeneration and macular degeneration.
Furthermore, it is well-within the ordinary skill in art to identify relevant mechanisms in a disease pathology to identify known suitable treatment candidates based on known properties.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Qian et. al.5
Regarding claim 1 and a compound of Formula 1-1D, Qian teaches fluorine substituted benzoxazoles as immunosuppressants, antifertility or herbicidal agents, or a treatment for Marek’s disease (see Qian at p. 138 left col.). Qian teaches the benzoxazoles CAS# 371914-79-3 and CAS# 371914-78-2 (see Qian at p. 138 Scheme 1 Compounds 2c and 2b).
Qian Compound 2c
CAS# 371914-79-3
Instant Claim 1 Formula 1-1D
CAS# 2991249-79-5
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Qian Compound 2b
CAS# 371914-78-2
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The prior art differs from the instant claims as follows: While Qian teaches CAS# 371914-79-3, CAS# 371914-79-3 does not have the same fluorine positions as CAS# 2991249-79-5.
However, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…isomers…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. Here, the prior art teaches a highly similar structural isomer, CAS# 371914-79-3, of the instantly claimed invention Formula 1-1D, differing only by two isomeric fluorine positions, one of which is taught by the prior art as a suitable fluorine position (see CAS# 371914-78-2). It would have been obvious to an artisan to attempt isomeric variations of a known compound when screening for suitable species for a targeted treatment, such as immunosuppressants, antifertility or herbicidal agents, or a treatment for Marek’s disease as taught by Qian, with a reasonable expectation of success because structurally similar species would be expected to have similar properties.
Furthermore, it is well-within the ordinary skill in art to make and use an isomer of a known compound.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
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 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 11-14, 18, 21-22 of copending Application No. 17/766,1746; instant claims 1-3, 6-7, 9-10 in view of Wermuth and instant claims 4, 8, 11-12 in further view of Kokkinaki.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Regarding claims 1-2 and a compound of Formula 1-1D or 1-1C, App’174 claims compounds of Formula 1 wherein L may be a bond and R4 and/or R5 may be a halogen such as fluorine (App’174 claims 1-4), including the species CAS# 2327998-93-4 (App’174 claim 5).
App’174 Chemical Formula 1
App’174 Claim 5 Species
CAS# 2327998-93-4
Instant Formula 1-1D
CAS# 2991249-79-5
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Regarding claims 3, 7 and compounds and increased expression of the klotho gene, App’174 claims a method of administering a composition comprising a compound of Formula 1 (App’174 claim 11), wherein the composition increases expression level of a klotho gene (App’174 claim 13).
Regarding claims 5-6, 9-10 and a composition, App’174 claims a method of inhibiting cellular senescence such as in renal proximal tubule epithelial cells (App’174 claim 12) or preventing or treating a vascular aging-induced disease comprising administering a composition comprising a compound of Formula 1 to a subject (App’174 claims 11, 18). App’174 also claims a cosmetic composition comprising a compound of Chemical Formula 1 (App’174 claim 14). App’174 also claims a method of treating or preventing a renal disease comprising administering a composition comprising a compound of Chemical Formula 1 (App’174 claims 22, 25).
The copending claims differ from the instant claims as follows: While App’174 claims structurally similar compounds in methods for increased expression of the klotho gene:
CAS# 2327998-93-4 differs from the instant species by H vs F,
App’174 does not specify the intended use of treating macular degeneration or protecting retinal pigment epithelial cells from oxidative stress
App’174 does not specify the property of protecting the retinal pigment epithelial cells from oxidative stress, and/or
App’174 does not specify the method of preventing or ameliorating macular degeneration.
However,
i) Regarding H vs F, App’174 claim 1 contemplates substitution at the R1 and R2 positions of Chemical Formula 1. Wermuth teaches fluorine for hydrogen isosterism often improves compounds in regards to metabolic degeneration (see Wermuth at p. 227 "(b) Electronic aspects").
ii) Regarding intended use, App’174 claims methods comprising compositions, or a cosmetic composition comprising CAS# 2327998-93-4. An artisan would appreciate the copending application compositions (a composition or cosmetic composition comprising a benzoxazole in a claimed method to increase expression of the klotho gene) are structurally similar to those instantly claimed (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) and are capable of being administered to a subject, and thus capable of performing the intended uses instantly claimed.
iii) Regarding claims 4, 8 and protecting retinal pigment epithelial cells, Kokkinaki teaches morphological changes in the retinal pigment epithelium (RPE) have been associated with retinal degenerative disorders (see Kokkinaki at Abstract). Kokkinaki also teaches the klotho gene protects against oxidative stress (see Kokkinaki at Title).
iv) Regarding claims 11-12 and a method of treating macular degeneration, Kokkinaki teaches aging-induced decline in phagocytosis is thought to contribute to age-related macular degeneration (see Kokkinaki at p. 16350 left col. ¶6).
iii) and iv) Regarding claims 4, 8, 11-12 and the nexus to the klotho gene, Kokkinaki teaches the klotho gene has a regulatory role in RPE phagocytosis and shows downregulation of the klotho gene inhibits phagocytosis in RPE cells (see Kokkinaki at p. 16356 right col. ¶1).
Kokkinaki thus teaches it was known in the art that increasing expression of the klotho gene can prevent or treat macular degeneration and protect retinal pigment epithelial cells against oxidative stress.
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the instantly claimed invention with a reasonable expectation of success in view of the copending claims for at least the following reason(s):
i) Regarding H vs F, per MPEP § 2143(I)(B), a prima facie case of obviousness exists for simple substitution of one known element for another to obtain predictable results. It would have been obvious to an artisan to modify App’174’s CAS# 2327998-93-4 to be substituted with fluorine in lieu of hydrogen with a reasonable expectation of success because the copending application contemplates substitution at the R1 and R2 positions (as claimed by App’174), and the prior art teaches the fluorine for hydrogen substitution can improve metabolic properties (as taught by Wermuth).
ii) Regarding intended use, App’174 a pharmaceutical or food composition comprising CAS# 2327998-93-4. An artisan would appreciate the prior art compositions (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) are structurally similar to those instantly claimed (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) and are capable of being administered to a subject, and thus capable of performing the intended uses instantly claimed.
iii) and iv) Regarding the property and methods, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. The copending application claims a highly similar structural benzoxazole to the instantly claimed invention, with a similar utility as the instantly claimed invention (increasing expression of the klotho gene); accordingly, an artisan would readily appreciate CAS# 2327998-93-4 (and its obvious variants), known to increase klotho gene expression, could be utilized in the treatment of macular degeneration or protecting RPE against oxidative stress, because the prior art teaches a decline in klotho gene expression leads to RPE degeneration and macular degeneration.
This is a provisional nonstatutory double patenting rejection.
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-9, 12 of copending Application No. 18/553,4147; instant claims 1-3, 6-7, 9-10 in view of Wermuth and instant claims 4, 8, 11-12 in further view of Kokkinaki.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Regarding claims 1-2 and a compound of Formula 1-1D or 1-1C, App’414 claims a method of treating neurodegenerative diseases comprising administering a pharmaceutical composition comprising a compound from the genus below (App’414 claims 1, 7), including the species CAS# 2327998-93-4 (App’414 claims 5, 12).
App’414 Claim 1 Formula
App’414 Claim 5 Species
CAS# 2327998-93-4
Instant Formula 1-1D
CAS# 2991249-79-5
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Regarding claims 3, 7 and compounds and increased expression of the klotho gene, App’414 claims a method of administering a composition comprising a compound of Formula 1 (App’414 claim 1), wherein the composition increases expression level of a klotho gene (App’414 claim 6).
Regarding claims 5-6, 9-10 and a composition, App’414 claims a health functional food composition for preventing or improving neurodegenerative disease comprising a compound of Chemical Formula 1 (App’414 claim 8) or a food composition for preventing or improving neurodegenerative disease comprising a compound of Chemical Formula 1 (App’414 claim 9), which encompasses CAS# 2327998-93-4.
App’414 Claim 8
Chemical Formula 1
App’414 Claim 5 Species
CAS# 2327998-93-4
Instant Formula 1-1D
CAS# 2991249-79-5
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The copending claims differ from the instant claims as follows: While App’414 claims structurally similar compounds in methods for increased expression of the klotho gene:
CAS# 2327998-93-4 differs from the instant species by H vs F,
App’414 does not specify the intended use of treating macular degeneration or protecting retinal pigment epithelial cells from oxidative stress
App’414 does not specify the property of protecting the retinal pigment epithelial cells from oxidative stress, and/or
App’414 does not specify the method of preventing or ameliorating macular degeneration.
However,
i) Regarding H vs F, App’414 claim 1 contemplates substitution at the R1 and R2 positions of the genus. Wermuth teaches fluorine for hydrogen isosterism often improves compounds in regards to metabolic degeneration (see Wermuth at p. 227 "(b) Electronic aspects").
ii) Regarding intended use, App’414 claims methods comprising pharmaceutical compositions, or food compositions, comprising CAS# 2327998-93-4. An artisan would appreciate the copending application compositions (a pharmaceutical composition or food composition comprising a benzoxazole in a claimed method to increase expression of the klotho gene) are structurally similar to those instantly claimed (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) and are capable of being administered to a subject, and thus capable of performing the intended uses instantly claimed.
iii) Regarding claims 4, 8 and protecting retinal pigment epithelial cells, Kokkinaki teaches morphological changes in the retinal pigment epithelium (RPE) have been associated with retinal degenerative disorders (see Kokkinaki at Abstract). Kokkinaki also teaches the klotho gene protects against oxidative stress (see Kokkinaki at Title).
iv) Regarding claims 11-12 and a method of treating macular degeneration, Kokkinaki teaches aging-induced decline in phagocytosis is thought to contribute to age-related macular degeneration (see Kokkinaki at p. 16350 left col. ¶6).
iii) and iv) Regarding claims 4, 8, 11-12 and the nexus to the klotho gene, Kokkinaki teaches the klotho gene has a regulatory role in RPE phagocytosis and shows downregulation of the klotho gene inhibits phagocytosis in RPE cells (see Kokkinaki at p. 16356 right col. ¶1).
Kokkinaki thus teaches it was known in the art that increasing expression of the klotho gene can prevent or treat macular degeneration and protect retinal pigment epithelial cells against oxidative stress.
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the instantly claimed invention with a reasonable expectation of success in view of the copending claims for at least the following reason(s):
i) Regarding H vs F, per MPEP § 2143(I)(B), a prima facie case of obviousness exists for simple substitution of one known element for another to obtain predictable results. It would have been obvious to an artisan to modify App’414’s CAS# 2327998-93-4 to be substituted with fluorine in lieu of hydrogen with a reasonable expectation of success because the copending application contemplates substitution at the R1 and R2 positions (as claimed by App’414), and the prior art teaches the fluorine for hydrogen substitution can improve metabolic properties (as taught by Wermuth).
ii) Regarding intended use, App’414 claims a pharmaceutical or food composition comprising CAS# 2327998-93-4. An artisan would appreciate the prior art compositions (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) are structurally similar to those instantly claimed (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) and are capable of being administered to a subject, and thus capable of performing the intended uses instantly claimed.
iii) and iv) Regarding the property and methods, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. The copending application claims a highly similar structural benzoxazole to the instantly claimed invention, with a similar utility as the instantly claimed invention (increasing expression of the klotho gene); accordingly, an artisan would readily appreciate CAS# 2327998-93-4 (and its obvious variants), known to increase klotho gene expression, could be utilized in the treatment of macular degeneration or protecting RPE against oxidative stress, because the prior art teaches a decline in klotho gene expression leads to RPE degeneration and macular degeneration.
This is a provisional nonstatutory double patenting rejection.
Claims 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,691,102 B28; instant claims 1-3, 6-7, 9-10 in view of Wermuth and instant claims 4, 8, 11-12 in further view of Kokkinaki.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Regarding claims 1-2 and a compound of Formula 1-1D or 1-1C, US’102 claims a method for preventing or treating chronic kidney disease comprising administering a pharmaceutical composition comprising a compound of Chemical Formula 1 (US’102 claims 1-4, 8-9) such as CAS# 2327998-93-4 (US’102 claim 5), or Chemical Formula 1-1 (wherein L1 is a bond) (US’102 claim 6), which also encompasses CAS# 2327998-93-4.
US’102 Claim 1
Chemical Formula 1
US’102 Claim 5 Species
CAS# 2327998-93-4
Instant Formula 1-1D
CAS# 2991249-79-5
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Regarding claims 3, 7 and compounds and increased expression of the klotho gene, US’102 claims wherein the method of claim 1 increases the expression level of a klotho gene (US’102 claim 7).
Regarding claims 5-6, 9-10 and a composition, US’102 claims a method for preventing or treating chronic kidney disease comprising administering a pharmaceutical composition comprising a compound of Chemical Formula 1 (US’102 claims 1-4, 8-9).
The patented claims differ from the instant claims as follows: While US’102 claims structurally similar compounds in methods for increased expression of the klotho gene:
CAS# 2327998-93-4 differs from the instant species by H vs F,
US’102 does not specify the intended use of treating macular degeneration or protecting retinal pigment epithelial cells from oxidative stress
US’102 does not specify the property of protecting the retinal pigment epithelial cells from oxidative stress, and/or
US’102 does not specify the method of preventing or ameliorating macular degeneration.
However,
i) Regarding H vs F, US’102 claim 1 contemplates substitution at the R1 and R2 positions of the genus. Wermuth teaches fluorine for hydrogen isosterism often improves compounds in regards to metabolic degeneration (see Wermuth at p. 227 "(b) Electronic aspects").
ii) Regarding intended use, US’102 claims methods comprising pharmaceutical compositions comprising CAS# 2327998-93-4. An artisan would appreciate the copending application compositions (a pharmaceutical composition comprising a benzoxazole in a claimed method to increase expression of the klotho gene) are structurally similar to those instantly claimed (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) and are capable of being administered to a subject, and thus capable of performing the intended uses instantly claimed.
iii) Regarding claims 4, 8 and protecting retinal pigment epithelial cells, Kokkinaki teaches morphological changes in the retinal pigment epithelium (RPE) have been associated with retinal degenerative disorders (see Kokkinaki at Abstract). Kokkinaki also teaches the klotho gene protects against oxidative stress (see Kokkinaki at Title).
iv) Regarding claims 11-12 and a method of treating macular degeneration, Kokkinaki teaches aging-induced decline in phagocytosis is thought to contribute to age-related macular degeneration (see Kokkinaki at p. 16350 left col. ¶6).
iii) and iv) Regarding claims 4, 8, 11-12 and the nexus to the klotho gene, Kokkinaki teaches the klotho gene has a regulatory role in RPE phagocytosis and shows downregulation of the klotho gene inhibits phagocytosis in RPE cells (see Kokkinaki at p. 16356 right col. ¶1).
Kokkinaki thus teaches it was known in the art that increasing expression of the klotho gene can prevent or treat macular degeneration and protect retinal pigment epithelial cells against oxidative stress.
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the instantly claimed invention with a reasonable expectation of success in view of the copending claims for at least the following reason(s):
i) Regarding H vs F, per MPEP § 2143(I)(B), a prima facie case of obviousness exists for simple substitution of one known element for another to obtain predictable results. It would have been obvious to an artisan to modify US’102’s CAS# 2327998-93-4 to be substituted with fluorine in lieu of hydrogen with a reasonable expectation of success because the copending application contemplates substitution at the R1 and R2 positions (as claimed by US’102) and the prior art teaches the fluorine for hydrogen substitution can improve metabolic properties (as taught by Wermuth).
ii) Regarding intended use, US’102 claims a pharmaceutical or food composition comprising CAS# 2327998-93-4. An artisan would appreciate the prior art compositions (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) are structurally similar to those instantly claimed (a pharmaceutical or food composition comprising a benzoxazole known to increase expression of the klotho gene) and are capable of being administered to a subject, and thus capable of performing the intended uses instantly claimed.
iii) and iv) Regarding the property and methods, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. The copending application claims a highly similar structural benzoxazole to the instantly claimed invention, with a similar utility as the instantly claimed invention (increasing expression of the klotho gene); accordingly, an artisan would readily appreciate CAS# 2327998-93-4 (and its obvious variants), known to increase klotho gene expression, could be utilized in the treatment of macular degeneration or protecting RPE against oxidative stress, because the prior art teaches a decline in klotho gene expression leads to RPE degeneration and macular degeneration.
Accordingly, the instant claims are not patentably distinct over US’102.
Conclusion
Claims 1-12 are rejected.
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/SOPHIA REILLY/Examiner, Art Unit 1627
1 Published April 8, 2021. Published October 5, 2020. Hereinafter WO’608.
2 Machine Translation of WO 2021066608 A1, Translated by Patent Translate Espacenet.org on 9/8/26, 209 pages. Hereinafter WO’608T.
3 Wermuth, Camille. “Molecular Variations Based on Isosteric Replacements” in The Practice of Medicinal Chemistry, 1st ed., Academic Press, 1996, pp.203-237. Hereinafter Wermuth.
4 Kokkinaki et. al. "Klotho Regulates Retinal Pigment Epithelial Functions and Protects Against Oxidative Stress" Journal of Neuroscience 2013, 33, 41, 16346-16359. DOI: 10.1523/JNEUROSCI.0402-13.2013. Hereinafter Kokkinaki.
5 Qian et. al. "Yellow HgO as an efficient cyclodesulfurising agent inthe synthesis of 2-substituted aminobenzoxazolesfrom N-(2-hydroxyphenyl)-N’- phenylthioureas" Journal of Chemical Research Synopses, 2001, 4, 138-139. DOI: 10.3184/030823401103169441. Hereinafter Qian.
6 371 of PCT/KR2020/013480 filed October 5, 2020. Hereinafter App’174.
7 371 of PCT/KR2022/004341 filed March 28, 2022. Hereinafter App’414.
8 Patented July 28, 2026. Hereinafter US’102.
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