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 .
New Examiner
The new examiner of record is Erin Hirt.
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.
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) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Stache (US3663579) in view of PT1296645 E.
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1-10, Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document); wherein, in particular, Stache teaches a dimeric steroid of 9-alpha-fluoro-16-alpha-methylprednisolone (i.e., carbonate dimer of dexamethasone) prepared from the reaction of 9-alpha-fluoro-16-alpha-methyl prednisolone (also called: dexamethasone) with triethylene glycol-bis-chloro-formiate (e.g., Triethylene glycol bis(chloroformate) shown below):
Triethylene glycol bis(chloroformate)
Dexamethasone
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(See example 3; col.5, lns,1-22) to provide the dimeric steroidal compound as represented by the structure in claim 28.
Generally, Stache teaches dimeric steroid (e.g. corticosteroid) 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document; claims; examples; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50);
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wherein R1 can be an open-chain alkylene where the open-chain alkylene can be interrupted by oxygen atom (col.1, lns.15-55; see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; examples, claims), and for instance when the O-R1-O- group of Stache is the claimed L group and is formed from Triethylene glycol bis(chloroformate) of Stache, the O-CH2-CH2-O-CH2-CH2-O-CH2-CH2-O which makes up L has a MW of ~148 which reads on the claimed 80-800 Da. Stache explicitly teaches that the dimeric steroids have superior anti-inflammatory activity in comparison to their corresponding monomeric compound (col.3, lns.42-75; Col. 4, ln. 30-36; see entire document; claims; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50).
Regarding claim 10, as discussed above Stache teaches wherein the steroids can be the same as each other and/or different (See entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims).
Regarding claims 9, 13 and 14, Stache teaches wherein the steroid/corticosteroid is not particularly limited and can include the claimed prednisolone (see example 8), and the claimed dimer of claim 14 wherein prednisolone has formed a dimer with the Triethylene glycol bis(chloroformate) (see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims; Col. 4, ln. 30-36).
Ascertainment of the difference between prior art and the claims
(MPEP 2141.02)
Regarding the instant claims 1-20, Stache does not teach wherein the dimer steroid is in the form of an implant and present in amounts of at least 60% by weight of the implant. Stache also does not teach a method of treating an inflammatory disease, specifically by administering an implant comprising the claimed dimer, specifically locally, or specifically to an eye of a subject in need of said treatment, more specifically to the cavity of an eye of a subject in need of said treatment. Stache also does not teach wherein each of the steroids are the claimed triamcinolone or the specific dimer of claims 12 and 16.
PT1296645 E cures these deficiencies.
PT1296645 E teaches implants for the eye, specifically for implanting into the vitreous cavity which comprise/can comprise at least 60% of steroid, e.g. about 70% by weight of steroid, which are implanted into the vitreous cavity with biodegradable polymers to provide release and subsequent reabsorption over 5 weeks, and they also teach wherein the steroids/corticosteroids which can be administered via these implants include the instantly claimed prednisolone, prednisone, triamcinolone, and triamcinolone acetonide (See entire document; examples, especially examples 3-5 which are administered to vitreous cavity; all claims, but specifically claim 7, see paragraph/section beginning: Preferably, the steroid anti-inflammatory agent is selected from the group consisting of 21-acetoxy-pregnenolone, alclometasone, …through end of section with last sentence: In another embodiment the bioerodible implant comprises more than one steroidal anti-inflammatory agent.;). PT1296645 E further teaches a release profile which appears to read on that instantly claimed wherein they get at least about 50% drug release in 2 weeks and 1/10 of 2 weeks is 1.4 days when measured in immersion conditions in vitro and wherein the implant can release at least about 15% of drug at 1 week which would appear to make t10 greater than or equal to 1/10 of t50 (it takes greater than 1.4 days for the implant to release 10% of the drug load) (See all sections cited above; see also paragraph/section beginning: In a preferred embodiment, a solid bioerodible implant is provided for the treatment of an inflammation-mediated problem of the eye, consisting essentially of: dexamethasone particles entrapped in a copolymer of polylactic acid and polyglycolic acid (PLGA)…end of paragraph/section.; tables, e.g. tables 6-7; examples, examples 3-5).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art at the time of the instant invention to have form the claimed steroid dimers as taught by Stache with triamcinolone and/or triamcinolone acetonide as claimed in claims 11-12 and 16. One of ordinary skill in the art would have been motivated to use these steroids to form the dimer in Stache because Stache teaches that forming the claimed dimers of corticosteroids makes the steroids more effective than the single compounds not in dimer form and PT1296645 E teaches that it was known to dose various corticosteroids including those instantly claimed and taught by Stache via biodegradable implants to the eye. Thus, one of ordinary skill in the art would formulate other known corticosteroids, e.g. the claimed triamcinolone and/or triamcinolone acetonide as the claimed dimers as is taught by Stache in order to form more effective forms of triamcinolone and triamcinolone acetonide for delivery via implant to the eye.
Additionally, it would have been obvious to replace the steroids of PT1296645 E for the dimers instantly claimed which are taught by Stache in order to form more effective extended release biodegradable and reabsorbable implants for use in the eye. One of ordinary skill in the art would be motivated to do this because Stache teaches that the dimers are more active that the steroids alone. It also would have been obvious to load the implants of PT1296645 E with the same percentages of dimer steroids of Stache that are instantly claimed because PT1296645 E already teaches using these claimed amounts of steroids in their own implants. Further, it would have been obvious to optimize the amounts of drug in the implant with the biodegradable polymers in order to achieve the claimed release profiles instantly claimed because PT1296645 E teaches that their implants can already achieve results similar
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26, and 29 of U.S. Patent No. 10632075 (‘075) in view of PT1296645 E and Stache (both cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘075 teaches the same implants having the same steroid dimers with the same release profiles instantly claimed and further teaches administering their implants locally specifically in the eye/intraocularly to treat inflammation, etc. as claimed. ‘075 does not teach wherein the implant is administered in a cavity of an eye of the subject in need thereof. However, this deficiency in ‘075 is addressed by PT1296645 E and Stache.
PT1296645 E teaches implants for the eye, specifically for implanting into the vitreous cavity which comprise/can comprise at least 60% of steroid, e.g. about 70% by weight of steroid, which are implanted into the vitreous cavity with biodegradable polymers to provide release and subsequent reabsorption over 5 weeks, and they also teach wherein the steroids/corticosteroids which can be administered via these implants include the instantly claimed prednisolone, prednisone, triamcinolone, and triamcinolone acetonide (See entire document; examples, especially examples 3-5 which are administered to vitreous cavity; all claims, but specifically claim 7, see paragraph/section beginning: Preferably, the steroid anti-inflammatory agent is selected from the group consisting of 21-acetoxy-pregnenolone, alclometasone, …through end of section with last sentence: In another embodiment the bioerodible implant comprises more than one steroidal anti-inflammatory agent.;). PT1296645 E further teaches a release profile which appears to read on that instantly claimed wherein they get at least about 50% drug release in 2 weeks and 1/10 of 2 weeks is 1.4 days when measured in immersion conditions in vitro and wherein the implant can release at least about 15% of drug at 1 week which would appear to make t10 greater than or equal to 1/10 of t50 (it takes greater than 1.4 days for the implant to release 10% of the drug load) (See all sections cited above; see also paragraph/section beginning: In a preferred embodiment, a solid bioerodible implant is provided for the treatment of an inflammation-mediated problem of the eye, consisting essentially of: dexamethasone particles entrapped in a copolymer of polylactic acid and polyglycolic acid (PLGA)…end of paragraph/section.; tables, e.g. tables 6-7; examples, examples 3-5).
Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document); wherein, in particular, Stache teaches a dimeric steroid of 9-alpha-fluoro-16-alpha-methylprednisolone (i.e., carbonate dimer of dexamethasone) prepared from the reaction of 9-alpha-fluoro-16-alpha-methyl prednisolone (also called: dexamethasone) with triethylene glycol-bis-chloro-formiate (e.g., Triethylene glycol bis(chloroformate) shown below):
Triethylene glycol bis(chloroformate)
Dexamethasone
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(See example 3; col.5, lns,1-22) to provide the dimeric steroidal compound as represented by the structure in claim 28.
Generally, Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document; claims; examples; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50);
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wherein R1 can be an open-chain alkylene where the open-chain alkylene can be interrupted by oxygen atom (col.1, lns.15-55; see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; examples, claims), and for instance when the O-R1-O- group of Stache is the claimed L group and is formed from Triethylene glycol bis(chloroformate) of Stache, the O-CH2-CH2-O-CH2-CH2-O-CH2-CH2-O which makes up L has a MW of ~148 which reads on the claimed 80-800 Da. Stache explicitly teaches that the dimeric steroids have superior anti-inflammatory activity in comparison to their corresponding monomeric compound (col.3, lns.42-75; Col. 4, ln. 30-36; see entire document; claims; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50).
Regarding claim 10, as discussed above Stache teaches wherein the steroids can be the same as each other and/or different (See entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims).
Regarding claims 13 and 14, Stache teaches wherein the steroid/corticosteroid is not particularly limited and can include the claimed prednisolone (see example 8), and the claimed dimer of claim 14 wherein prednisolone has formed a dimer with the Triethylene glycol bis(chloroformate) (see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims; Col. 4, ln. 30-36).
Thus, one of ordinary skill in the art would be motivated to form the claimed implants, methods, etc. when looking to the combined teachings of US10632075 in view of the secondary references cited herein because each and every feature of the claimed implants was already known in the art to be useful for forming implants for use in the claimed parts of the eye and/or providing improved steroid activity with the use of the dimer as discussed herein.
Thus, one of ordinary skill in the art would conclude that the instantly claimed invention is rendered obvious by the combined teachings of US10632075 in view of the secondary references cited herein.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19, 21-23, 26-44, 46-48 of U.S. Patent No. 10588862 (‘862) in view of PT1296645 E and Stache (both cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘862 teaches the same implants having the same steroid dimers with the same release profiles instantly claimed and further teaches administering their implants locally specifically in the eye/intraocularly to treat inflammation, etc. as claimed. ‘862 does not teach wherein the dimer steroid is the claimed triamcinolone or triamcinolone acetonide, etc. or wherein the implant is administered in a cavity of an eye of the subject in need thereof. However, this deficiency in ‘075 is addressed by PT1296645 E and Stache.
PT1296645 E teaches implants for the eye, specifically for implanting into the vitreous cavity which comprise/can comprise at least 60% of steroid, e.g. about 70% by weight of steroid, which are implanted into the vitreous cavity with biodegradable polymers to provide release and subsequent reabsorption over 5 weeks, and they also teach wherein the steroids/corticosteroids which can be administered via these implants include the instantly claimed prednisolone, prednisone, triamcinolone, and triamcinolone acetonide (See entire document; examples, especially examples 3-5 which are administered to vitreous cavity; all claims, but specifically claim 7, see paragraph/section beginning: Preferably, the steroid anti-inflammatory agent is selected from the group consisting of 21-acetoxy-pregnenolone, alclometasone, …through end of section with last sentence: In another embodiment the bioerodible implant comprises more than one steroidal anti-inflammatory agent.;). PT1296645 E further teaches a release profile which appears to read on that instantly claimed wherein they get at least about 50% drug release in 2 weeks and 1/10 of 2 weeks is 1.4 days when measured in immersion conditions in vitro and wherein the implant can release at least about 15% of drug at 1 week which would appear to make t10 greater than or equal to 1/10 of t50 (it takes greater than 1.4 days for the implant to release 10% of the drug load) (See all sections cited above; see also paragraph/section beginning: In a preferred embodiment, a solid bioerodible implant is provided for the treatment of an inflammation-mediated problem of the eye, consisting essentially of: dexamethasone particles entrapped in a copolymer of polylactic acid and polyglycolic acid (PLGA)…end of paragraph/section.; tables, e.g. tables 6-7; examples, examples 3-5).
Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document); wherein, in particular, Stache teaches a dimeric steroid of 9-alpha-fluoro-16-alpha-methylprednisolone (i.e., carbonate dimer of dexamethasone) prepared from the reaction of 9-alpha-fluoro-16-alpha-methyl prednisolone (also called: dexamethasone) with triethylene glycol-bis-chloro-formiate (e.g., Triethylene glycol bis(chloroformate) shown below):
Triethylene glycol bis(chloroformate)
Dexamethasone
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(See example 3; col.5, lns,1-22) to provide the dimeric steroidal compound as represented by the structure in claim 28.
Generally, Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document; claims; examples; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50);
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wherein R1 can be an open-chain alkylene where the open-chain alkylene can be interrupted by oxygen atom (col.1, lns.15-55; see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; examples, claims), and for instance when the O-R1-O- group of Stache is the claimed L group and is formed from Triethylene glycol bis(chloroformate) of Stache, the O-CH2-CH2-O-CH2-CH2-O-CH2-CH2-O which makes up L has a MW of ~148 which reads on the claimed 80-800 Da. Stache explicitly teaches that the dimeric steroids have superior anti-inflammatory activity in comparison to their corresponding monomeric compound (col.3, lns.42-75; Col. 4, ln. 30-36; see entire document; claims; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50).
As discussed above Stache teaches wherein the steroids can be the same as each other and/or different (See entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims).
Stache teaches wherein the steroid/corticosteroid is not particularly limited and can include the claimed prednisolone (see example 8), and the claimed dimer of claim 14 wherein prednisolone has formed a dimer with the Triethylene glycol bis(chloroformate) (see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims; Col. 4, ln. 30-36).
Thus, one of ordinary skill in the art would be motivated to form the claimed implants, methods, etc. when looking to the combined teachings of US10588862 in view of the secondary references cited herein because each and every feature of the claimed implants was already known in the art to be useful for forming implants for use in the claimed parts of the eye and/or providing improved steroid activity with the use of the dimer as discussed herein.
Thus, one of ordinary skill in the art would conclude that the instantly claimed invention is rendered obvious by the combined teachings of US10588862 in view of the secondary references cited herein.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 16-18 of U.S. Patent No. 10959954 (‘954) in view of PT1296645 E and Stache (both cited above) for the same/similar reasons which are discussed above with respect to U.S. Patent No. 10588862 (‘862) in view of PT1296645 E and Stache (both cited above).
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8-14, 16-18 of U.S. Patent No. 10945958 (‘958) in view of PT1296645 E and Stache (both cited above) for the same/similar reasons which are discussed above with respect to U.S. Patent No. 10588862 (‘862) in view of PT1296645 E and Stache (both cited above).
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 28-36, 40-42, and 44 of copending application No. 17629733 in view of PT1296645 E and Stache (both cited above) for the same/similar reasons which are discussed above with respect to U.S. Patent No. 10588862 (‘862) in view of PT1296645 E and Stache (both cited above).
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 129-146 of copending 18992519 in view of PT1296645 E and Stache (both cited above) because ‘519 teaches methods of using the claimed dimers in implants having the claimed release profile since it comprises the same amount of the same drugs and is formed in the same manner instantly disclosed and wherein the dimer steroid is dexamethasone and is injected into the eye, specifically the intravitreal cavity in the eye. ‘519 does not teach wherein the steroids are the other steroids instantly claimed. However, these steroids and other features instantly claimed which are not taught by ‘519 are taught by the combination of PT1296645 E and Stache.
PT1296645 E teaches implants for the eye, specifically for implanting into the vitreous cavity which comprise/can comprise at least 60% of steroid, e.g. about 70% by weight of steroid, which are implanted into the vitreous cavity with biodegradable polymers to provide release and subsequent reabsorption over 5 weeks, and they also teach wherein the steroids/corticosteroids which can be administered via these implants include the instantly claimed prednisolone, prednisone, triamcinolone, and triamcinolone acetonide (See entire document; examples, especially examples 3-5 which are administered to vitreous cavity; all claims, but specifically claim 7, see paragraph/section beginning: Preferably, the steroid anti-inflammatory agent is selected from the group consisting of 21-acetoxy-pregnenolone, alclometasone, …through end of section with last sentence: In another embodiment the bioerodible implant comprises more than one steroidal anti-inflammatory agent.;). PT1296645 E further teaches a release profile which appears to read on that instantly claimed wherein they get at least about 50% drug release in 2 weeks and 1/10 of 2 weeks is 1.4 days when measured in immersion conditions in vitro and wherein the implant can release at least about 15% of drug at 1 week which would appear to make t10 greater than or equal to 1/10 of t50 (it takes greater than 1.4 days for the implant to release 10% of the drug load) (See all sections cited above; see also paragraph/section beginning: In a preferred embodiment, a solid bioerodible implant is provided for the treatment of an inflammation-mediated problem of the eye, consisting essentially of: dexamethasone particles entrapped in a copolymer of polylactic acid and polyglycolic acid (PLGA)…end of paragraph/section.; tables, e.g. tables 6-7; examples, examples 3-5).
Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document); wherein, in particular, Stache teaches a dimeric steroid of 9-alpha-fluoro-16-alpha-methylprednisolone (i.e., carbonate dimer of dexamethasone) prepared from the reaction of 9-alpha-fluoro-16-alpha-methyl prednisolone (also called: dexamethasone) with triethylene glycol-bis-chloro-formiate (e.g., Triethylene glycol bis(chloroformate) shown below):
Triethylene glycol bis(chloroformate)
Dexamethasone
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(See example 3; col.5, lns,1-22) to provide the dimeric steroidal compound as represented by the structure in claim 28.
Generally, Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document; claims; examples; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50);
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wherein R1 can be an open-chain alkylene where the open-chain alkylene can be interrupted by oxygen atom (col.1, lns.15-55; see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; examples, claims), and for instance when the O-R1-O- group of Stache is the claimed L group and is formed from Triethylene glycol bis(chloroformate) of Stache, the O-CH2-CH2-O-CH2-CH2-O-CH2-CH2-O which makes up L has a MW of ~148 which reads on the claimed 80-800 Da. Stache explicitly teaches that the dimeric steroids have superior anti-inflammatory activity in comparison to their corresponding monomeric compound (col.3, lns.42-75; Col. 4, ln. 30-36; see entire document; claims; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50).
As discussed above Stache teaches wherein the steroids can be the same as each other and/or different (See entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims).
Stache teaches wherein the steroid/corticosteroid is not particularly limited and can include the claimed prednisolone (see example 8), and the claimed dimer of claim 14 wherein prednisolone has formed/can be formed into a dimer with the Triethylene glycol bis(chloroformate) as is claimed (see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims; Col. 4, ln. 30-36). Thus, one of ordinary skill in the art would be motivated to form the claimed implants, methods, etc. when looking to the combined teachings of copending 18992519 in view of the secondary references cited herein because each and every feature of the claimed implants was already known in the art to be useful for forming implants for use in the claimed parts of the eye and/or providing improved steroid activity with the use of the dimer as discussed herein.
Thus, one of ordinary skill in the art would conclude that the instantly claimed invention is rendered obvious by the combined teachings of copending 18992519 in view of the secondary references cited herein.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-12 of US12473326 in view of PT1296645 E and Stache (both cited above). ‘326 teaches the claimed steroid dimers and articles/implants comprising these dimers in the claimed percentages but does not teach wherein the steroid is other than dimethazone or the claimed methods of use, etc. as claimed.
Regarding claims 1-10, Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document); wherein, in particular, Stache teaches a dimeric steroid of 9-alpha-fluoro-16-alpha-methylprednisolone (i.e., carbonate dimer of dexamethasone) prepared from the reaction of 9-alpha-fluoro-16-alpha-methyl prednisolone (also called: dexamethasone) with triethylene glycol-bis-chloro-formiate (e.g., Triethylene glycol bis(chloroformate) shown below):
Triethylene glycol bis(chloroformate)
Dexamethasone
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115
270
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221
366
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(See example 3; col.5, lns,1-22) to provide the dimeric steroidal compound as represented by the structure in claim 28.
Generally, Stache teaches dimeric steroid 21-alkyl-carbonates as represented by the structure of formula I (col.1, lns.15-54; See entire document; claims; examples; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50);
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274
389
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wherein R1 can be an open-chain alkylene where the open-chain alkylene can be interrupted by oxygen atom (col.1, lns.15-55; see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; examples, claims), and for instance when the O-R1-O- group of Stache is the claimed L group and is formed from Triethylene glycol bis(chloroformate) of Stache, the O-CH2-CH2-O-CH2-CH2-O-CH2-CH2-O which makes up L has a MW of ~148 which reads on the claimed 80-800 Da. Stache explicitly teaches that the dimeric steroids have superior anti-inflammatory activity in comparison to their corresponding monomeric compound (col.3, lns.42-75; Col. 4, ln. 30-36; see entire document; claims; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50).
Regarding claim 10, as discussed above Stache teaches wherein the steroids can be the same as each other and/or different (See entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims).
Regarding claims 13 and 14, Stache teaches wherein the steroid/corticosteroid is not particularly limited and can include the claimed prednisolone (see example 8), and the claimed dimer of claim 14 wherein prednisolone has formed a dimer with the Triethylene glycol bis(chloroformate) (see entire document; Col. 1, ln. 20-Col. 2, ln. 65; Col. 2, ln. 71-Col. 3, ~ln. 50; Examples; claims; Col. 4, ln. 30-36).
PT1296645 E teaches implants for the eye, specifically for implanting into the vitreous cavity which comprise/can comprise at least 60% of steroid, e.g. about 70% by weight of steroid, which are implanted into the vitreous cavity with biodegradable polymers to provide release and subsequent reabsorption over 5 weeks, and they also teach wherein the steroids/corticosteroids which can be administered via these implants include the instantly claimed prednisolone, prednisone, triamcinolone, and triamcinolone acetonide (See entire document; examples, especially examples 3-5 which are administered to vitreous cavity; all claims, but specifically claim 7, see paragraph/section beginning: Preferably, the steroid anti-inflammatory agent is selected from the group consisting of 21-acetoxy-pregnenolone, alclometasone, …through end of section with last sentence: In another embodiment the bioerodible implant comprises more than one steroidal anti-inflammatory agent.). PT1296645 E further teaches a release profile which appears to read on that instantly claimed wherein they get at least about 50% drug release in 2 weeks and 1/10 of 2 weeks is 1.4 days when measured in immersion conditions in vitro and wherein the implant can release at least about 15% of drug at 1 week which would appear to make t10 greater than or equal to 1/10 of t50 (it takes greater than 1.4 days for the implant to release 10% of the drug load) (See all sections cited above; see also paragraph/section beginning: In a preferred embodiment, a solid bioerodible implant is provided for the treatment of an inflammation-mediated problem of the eye, consisting essentially of: dexamethasone particles entrapped in a copolymer of polylactic acid and polyglycolic acid (PLGA)…end of paragraph/section.; tables, e.g. tables 6-7; examples, examples 3-5).
It would have been obvious to one of ordinary skill in the art at the time of the instant invention to have form the claimed steroid dimers as taught by Stache with triamcinolone and/or triamcinolone acetonide as claimed in claims 11-12 and 16 for use in the articles of US ‘326. One of ordinary skill in the art would have been motivated to use these steroids to form the dimer in the articles of ‘326 and Stache because Stache teaches that forming the claimed dimers of corticosteroids makes the steroids more effective than the single compounds not in dimer form and PT1296645 E teaches that it was known to dose various corticosteroids including those instantly claimed and taught by ‘326 and Stache via biodegradable implants to the eye. Thus, one of ordinary skill in the art would formulate other known corticosteroids, e.g. the claimed triamcinolone and/or triamcinolone acetonide as the claimed dimers as is taught by ‘326 and Stache in order to form more effective forms of triamcinolone and triamcinolone acetonide for delivery via implant to the eye.
Additionally, it would have been obvious to replace the steroids of PT1296645 E and the articles of ‘326 for the dimers instantly claimed which are taught by Stache in order to form more effective extended release biodegradable and reabsorbable implants for use in the eye. One of ordinary skill in the art would be motivated to do this because Stache teaches that the dimers are more active that the steroids alone. It also would have been obvious to load the implants and articles of PT1296645 E and ‘326 with the same percentages of dimer steroids of Stache that are instantly claimed because PT1296645 E already teaches using these claimed amounts of steroids in their own implants. Further, it would have been obvious to optimize the amounts of drug in the implants taught by ‘326 and PT1296645E with the biodegradable polymers in order to achieve the claimed release profiles instantly claimed because PT1296645 E teaches that their implants can already achieve results similar to those instantly claimed.
Response to Arguments/Remarks
Applicant’s terminal disclaimers have overcome the double patenting rejections over 11612567 and copending 19443638 which are hereby withdrawn. The new examiner of record has upon further consideration issued the instant second non-final office action and additional double patenting rejections and does not agree with the previous examiner’s indications of allowable subject matter based upon her updated search. Thus, the new examiner apologizes but the instant claims are not in condition for allowance at this time for the above discussed reasons.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin E Hirt whose telephone number is (571)270-1077. The examiner can normally be reached 10:30-7:30 ET M-F.
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/ERIN E HIRT/Primary Examiner, Art Unit 1616
