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 371 of PCT/US22/34043, filed June 17, 2022, and claims the benefit of U.S. Provisional Application No. 63/211,936, filed June 17, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 19, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1, 9, 18, 22-23, 26-27, 30, 37-43, and 45-49 are currently pending and subject to examination.
Drawings
The drawings are objected to because they are blurry. The characters and lines are not sufficiently dark and clear. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
“Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.”
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim(s) recite(s) a method of disrupting protein interactions in an HDAC complex in a cell of a subject comprising administering to the subject an effective amount of a compound having the structure of Formula (I). This judicial exception is not integrated into a practical application because the claim does not require the treatment or prophylaxis of a particular disease or medical condition. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim does not recite any elements other than administering a compound to disrupt an HDAC complex in a subject.
Step 1: YES. The claims recite a process.
Step 2A: YES. The claim is directed towards a natural phenomenon: the response of HDAC complexes to a compound of formula (I).
Step 2B: NO. The claim does not recite additional elements that amount to significantly more than the judicial exception because the process is not directed towards the treatment or prophylaxis of a particular medical condition. The claim reads on observing the natural phenomenon of HDAC complex formation within cells.
Claim Rejections – 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
“A person shall be entitled to a patent unless -
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.”
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shaw et al. (US 2011/0160227 A1).
Claim 1 recites:
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Shaw teaches compounds falling within the genus of formula (I). For example:
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Shaw, Specification, para. [0076], example 1.
Shaw teaches administering an effective amount of a compound to a subject, wherein the effective amount is usually 1 to 10 mg/kg per day (Id., para. [0068]). This is identical to the typical amount recited in the instant specification (Instant spec., p. 46). As Shaw teaches a compound falling within the claimed genus, and administering an effective amount which is comparable to the effective amount of compounds of formula (I) for inhibiting HDAC complexes, HDAC complexes would inherently be inhibited during the normal and usual operation of the method of Shaw. “Under the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art device.” (MPEP § 2112.02).
Therefore, claim 1 is anticipated.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ukrainets et al. (Pharmaceutical Chemistry Journal, 52(7), p. 601-605 (2018)) (of record, IDS cite no. CI) as evidenced by Aly et al. (Molecular Diversity, Volume 24, p. 477–524, April 27, 2019).
Claim 1 recites:
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Ukrainets teaches to administer compounds within the scope of formula (I) for analgesia at an effective amount of 5 mg/kg PO:
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Ukrainets, p. 601, col. 2;
The analgesic activity of picolylamides IIa-l was studied in white mongrel male mice weighing 22 – 24 g (10 animals for each test compound), using a standard acetic acid writhing model [11]. Nociceptive effects were produced by i.p. injection of 0.6% acetic acid, 0.1 ml per 10 g body weight, 1 h after administration of test samples. Animals were observed for 20 min, counting the number of writhings. Analgesic activity was assessed in terms of the abilities of compounds to decrease the number of writhings in the study groups as compared with controls, and was expressed as a percentage (Table 5). Testing was performed in comparison with diclofenac (KRK, Slovenia). All test picolylamides IIa-l were given p.o. at a dose of 5 mg/kg as a fine aqueous suspension stabilized with tween-80. Diclofenac was used as aqueous solution at a dose of 5 mg/kg, which corresponds to its ED50 for this experimental model [12]. Control animals received the same volumes of water and tween-80. Results from all biological tests were analyzed statistically [13, 14].
Ukrainets, p. 604, col. 2.
While these compounds are displayed as tautomers of the compound of formula (I), the other tautomer is an inherent aspect of the compound, and would be acknowledged as inherent by a person of ordinary skill in the art as such, as it is well known in the art that such compounds exists in tautomeric equilibrium as evidenced by Aly, which teaches that similar compounds exist in tautomeric equilibrium:
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Aly, Fig. 1, p. 478.
While Ukrainets does not teach that these compounds inhibit HDAC activity, this would inherently result from the administration of the therapeutically effective amount of the compound (5 mg/kg). This falls within the oral therapeutically effective dose described in the specification: 0.5 to 50 mg/kg (instant specification, p. 46).
Therefore, claim 1 is anticipated.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ukrainets et al. (Journal of Organic and Pharmaceutical Chemistry, Vol. 13, Issue 4, p. 6-11 (2015)) (of record, IDS cite no. CH) as evidenced by Aly et al. (Molecular Diversity, Volume 24, p. 477–524, April 27, 2019).
Claim 1 recites:
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Ukrainets teaches to administer compounds within the scope of formula (I) for analgesia at an effective amount of 20 mg/kg PO:
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Ukrainets, p. 7;
The assessment of the analgesic effect was carried out by the ability of test substances to reduce the number of “writhings” in comparison with the un- treated control and expressed as a percentage (Table 3). The well-known non-narcotic analgesics Piroxi- cam and Nabumetone were used as the reference drugs. All N-(benzyl)-2-hydroxy-8-methyl-4-oxo-4H- pyrido[1,2-a]pyrimidine-3-carboxamides (5a-n) under study were introduced as a fine aqueous suspension stabilized with Tween-80 (20 mg/kg, orally).
Ukrainets, p. 10, col. 1.
While these compounds are displayed as tautomers of the compound of formula (I), the other tautomer is an inherent aspect of the compound, and would be acknowledged as inherent by a person of ordinary skill in the art as such, as it is well known in the art that such compounds exists in tautomeric equilibrium as evidenced by Aly, which teaches that similar compounds exist in tautomeric equilibrium:
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Aly, Fig. 1, p. 478.
While Ukrainets does not teach that these compounds inhibit HDAC activity, this would inherently result from the administration of the therapeutically effective amount of the compound (20 mg/kg). This falls within the oral therapeutically effective dose described in the specification: 0.5 to 50 mg/kg (instant specification, p. 46).
Therefore, claim 1 is anticipated.
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, 9, 22, 23, 26, 27, and 46-47 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ukrainets et al. (Pharmaceutical Chemistry Journal, 52(7), p. 601-605 (2018)) (of record, IDS cite no. CI) as evidenced by Aly et al. (Molecular Diversity, Volume 24, p. 477–524, April 27, 2019), as applied to claim 1 above, and further in view of Hedner et al. (Drugs, Vol. 64, p. 2315-2345 (2004)) as evidenced by Vojinovic & Damjanov (Molecular Medicine, Vol. 17, p. 397-403 (2011)).
The rejection of claim 1 above as anticipated by Ukrainets et al. (Pharmaceutical Chemistry Journal, 52(7), p. 601-605 (2018)) is incorporated herein by reference. As such, claim 1 was prima facie obvious at the time of filing.
Claim 9 is directed towards a method of treating a disease mediated by an HDAC complex in a subject in need thereof comprising administering to the subject an effective amount of a compound having the structure of formula (I):
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As shown in the rejection of claim 1, Ukrainets teaches to administer a compound within the scope of claim 1 for the treatment of pain. Ukrainets compares the compounds within the scope of formula (I) with diclofenac, a common prescription NSAID for arthritis pain, and demonstrates that they have similar or better analgesic efficacy in a mouse model of pain:
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Ukrainets, p. 604.
While Ukrainets does not specifically teach that the analgesic is for rheumatoid arthritis pain, one of ordinary skill in the art would have a reasonable expectation of success to apply the analgesic to rheumatoid arthritis pain because it is commonly known in the art that NSAIDs such as diclofenac, the comparator used by Ukrainets, are used to reduce pain and inflammation associated with rheumatoid arthritis.
For example, Hedner teaches that the NSAIDs nabumetone, aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen have comparable efficacy in the treatment of rheumatoid arthritis.
Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA.
The optimum oral dosage of nabumetone for OA patients is 1g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1g at bedtime is optimal, but an additional 0.5–1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen.
Hedner, p. 2230.
While Ukrainets does not teach that the rheumatoid arthritis pain is mediated by an HDAC complex, this is an inherent property of rheumatoid arthritis pain.
For example, Vojinovic teaches that givinostat, an HDAC inhibitor was effective to treat pain caused by juvenile idiopathic arthritis, and that HDAC inhibitors could be used to treat both rheumatoid arthritis and juvenile idiopathic arthritis:
Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are heterogeneous autoimmune diseases characterized by chronic joint inflammation. Methotrexate is used as the gold standard to treat rheumatoid arthritis, yet there are many patients in whom the disease cannot be controlled or who experience unacceptable intolerance. Most of the biologics currently used are effective, but mostly if combined with methotrexate. Long-term possible side effects, such as impaired host defense mechanisms against infection and lymphoma, are distinct disadvantages and a major concern of anticytokine therapies. Parenteral administration is a problem, particularly in children. Thus, there is a need to explore new treatment options. Here we review the properties of histone deacetylase inhibitors (HDACi) as they apply to rheumatoid arthritis by looking at effects on cytokine production, T-cell differentiation and the function of macrophages, dendritic cells, osteoblasts, osteoclasts and synovial fibroblasts. We also review the safety and efficacy of givinostat (ITF 2357) in the treatment of systemic onset juvenile idiopathic arthritis (SOJIA) and its influence on the cytokine networks in SOJIA. Givinostat is an orally active HDACi which was given to children with SOJIA. After 12 wk of treatment, there were significant benefits, particularly in reducing the pain and arthritic component of the disease and decreasing the neutrophilia. CD40L, IL-1α and IFNγ in whole blood lysates decreased at wks 2 and 4 compared with baseline levels. The clinical data are consistent with those from animal models of rheumatoid arthritis and suggest that trials with HDACi are promising as a safe oral alternative to anticytokines and methotrexate.
Vojinovic, Abstract (emphasis added);
Epigenetic alterations comprise heritable modifications of the DNA without any change in the base sequence of the genetic code (9,10). Histone acetylation is crucial for the control of gene expression while histone deacetylation leads to chromatin condensation and repression of gene transcription (11). Inhibition of HDAC activity can contribute to the immunopathology of RA and other immune-mediated inflammatory diseases (12,13) via epigenetic or nonepigenetic processes, influencing the dynamic regulation of intracellular signaling pathways. Detailed description of biochemistry and mode of action of HDACs and their inhibitors have been reviewed (14). RA and JIA are systemic disorders in which autoimmune chronic inflammation emerges from a variable combination of individual genetic predispositions for dysregulated immune responses (15). This could explain possible positive influences of epigenetic modifications on inflammatory gene responses. Numerous genes coding cytokines, chemokines and the expression of activating or inhibitory factors of immune cells are linked to persistence of chronic arthritis and result in functional changes in immunoregulatory and cell cycle networks (16). Recent knowledge about the importance of epigenetic modulations in immunopathogenesis of autoimmune diseases and the first encouraging results obtained in vitro and in vivo in animal models of arthritis, using epigenetic modulators have announced a possible new era in antirheumatic drug development (12,17,18).
Id., p. 397-98.
Therefore, claim 9 was prima facie obvious at the time of filing.
Claims 22, 23, 26, 27, and 46-47 read on the compounds of Vojinovic and are therefore prima facie obvious for the reasons given in the rejections of claims 1 and 9.
Claim(s) 1, 9, 22, 23, 27, 38-43, and 45-49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ukrainets et al. (Journal of Organic and Pharmaceutical Chemistry, Vol. 13, Issue 4, p. 6-11 (2015)) (of record, IDS cite no. CH) as evidenced by Aly et al. (Molecular Diversity, Volume 24, p. 477–524, April 27, 2019), as applied to claim 1 above, and further in view of Hedner et al. (Drugs, Vol. 64, p. 2315-2345 (2004)) as evidenced by Vojinovic & Damjanov (Molecular Medicine, Vol. 17, p. 397-403 (2011)).
The rejection of claim 1 above as anticipated by Ukrainets et al. (Journal of Organic and Pharmaceutical Chemistry, Vol. 13, Issue 4, p. 6-11 (2015)) is incorporated herein by reference. As such, claim 1 was prima facie obvious at the time of filing.
Claim 9 is directed towards a method of treating a disease mediated by an HDAC complex in a subject in need thereof comprising administering to the subject an effective amount of a compound having the structure of formula (I):
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As shown in the rejection of claim 1, Ukrainets teaches to administer a compound within the scope of claim 1 for the treatment of pain. Ukrainets compares the compounds within the scope of formula (I) with piroxicam and nabumetone and demonstrates that they have similar or better analgesic efficacy in a mouse model of pain:
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Ukrainets, p. 10.
While Ukrainets does not specifically teach that the analgesic is for rheumatoid arthritis pain, one of ordinary skill in the art would have a reasonable expectation of success to apply the analgesic to rheumatoid arthritis pain because it is commonly known in the art that NSAIDs such as piroxicam and nabumetone, the comparator used by Ukrainets, are used to reduce pain and inflammation associated with rheumatoid arthritis.
For example, Hedner teaches that the NSAIDs nabumetone, aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen have comparable efficacy in the treatment of rheumatoid arthritis:
Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA.
The optimum oral dosage of nabumetone for OA patients is 1g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1g at bedtime is optimal, but an additional 0.5–1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen.
Hedner, p. 2230.
While Ukrainets does not teach that rheumatoid arthritis pain is mediated by an HDAC complex, this is an inherent property of rheumatoid arthritis pain.
For example, Vojinovic teaches that givinostat, an HDAC inhibitor was effective to treat pain caused by juvenile idiopathic arthritis, and that HDAC inhibitors could be used to treat both rheumatoid arthritis and juvenile idiopathic arthritis:
Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are heterogeneous autoimmune diseases characterized by chronic joint inflammation. Methotrexate is used as the gold standard to treat rheumatoid arthritis, yet there are many patients in whom the disease cannot be controlled or who experience unacceptable intolerance. Most of the biologics currently used are effective, but mostly if combined with methotrexate. Long-term possible side effects, such as impaired host defense mechanisms against infection and lymphoma, are distinct disadvantages and a major concern of anticytokine therapies. Parenteral administration is a problem, particularly in children. Thus, there is a need to explore new treatment options. Here we review the properties of histone deacetylase inhibitors (HDACi) as they apply to rheumatoid arthritis by looking at effects on cytokine production, T-cell differentiation and the function of macrophages, dendritic cells, osteoblasts, osteoclasts and synovial fibroblasts. We also review the safety and efficacy of givinostat (ITF 2357) in the treatment of systemic onset juvenile idiopathic arthritis (SOJIA) and its influence on the cytokine networks in SOJIA. Givinostat is an orally active HDACi which was given to children with SOJIA. After 12 wk of treatment, there were significant benefits, particularly in reducing the pain and arthritic component of the disease and decreasing the neutrophilia. CD40L, IL-1α and IFNγ in whole blood lysates decreased at wks 2 and 4 compared with baseline levels. The clinical data are consistent with those from animal models of rheumatoid arthritis and suggest that trials with HDACi are promising as a safe oral alternative to anticytokines and methotrexate.
Vojinovic, Abstract (emphasis added);
Epigenetic alterations comprise heritable modifications of the DNA without any change in the base sequence of the genetic code (9,10). Histone acetylation is crucial for the control of gene expression while histone deacetylation leads to chromatin condensation and repression of gene transcription (11). Inhibition of HDAC activity can contribute to the immunopathology of RA and other immune-mediated inflammatory diseases (12,13) via epigenetic or nonepigenetic processes, influencing the dynamic regulation of intracellular signaling pathways. Detailed description of biochemistry and mode of action of HDACs and their inhibitors have been reviewed (14). RA and JIA are systemic disorders in which autoimmune chronic inflammation emerges from a variable combination of individual genetic predispositions for dysregulated immune responses (15). This could explain possible positive influences of epigenetic modifications on inflammatory gene responses. Numerous genes coding cytokines, chemokines and the expression of activating or inhibitory factors of immune cells are linked to persistence of chronic arthritis and result in functional changes in immunoregulatory and cell cycle networks (16). Recent knowledge about the importance of epigenetic modulations in immunopathogenesis of autoimmune diseases and the first encouraging results obtained in vitro and in vivo in animal models of arthritis, using epigenetic modulators have announced a possible new era in antirheumatic drug development (12,17,18).
Id., p. 397-98.
Therefore, claim 9 was prima facie obvious at the time of filing.
Claims 22, 23, 27, 38-43, and 45-49 read on the compounds of Ukrainets and are therefore prima facie obvious for the reasons given in the rejection of claim 9.
Claim(s) 9, 18, 22-23, 26-27, 37-43, 45, and 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tripathi et al. (Journal of Molecular Graphics and Modelling, Volume 86, January 2019, Pages 1-18) (of record, IDS cite no. CE) as evidenced by Aly et al. (Molecular Diversity, Volume 24, p. 477–524, April 27, 2019).
Claim 9 is directed towards a method of treating a disease mediated by an HDAC complex in a subject in need thereof comprising administering to the subject an effective amount of a compound having the structure of formula (I):
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Claim 18 is directed towards the method of claim 9, wherein the disease mediated by a HDAC complex is selected from a cancer, a neurodegenerative disease and a mental disorder.
One of ordinary skill in the art would have a reasonable expectation of success to administer the compound of formula (I) in an effective amount to treat a cancer because Tripathi teaches the compounds of formula (I) are expected to have anticancer activity:
The unique hTopoIIα-catalytic inhibitory potential of merbarone can be efficiently explored for the identification of novel compounds as anti-hTopoIIα agents. With this motive, the details of delineated interactions between merbarone and hTopoIIα have been utilized as a crucial feature for the identification of new compounds with anticancer potential. To identify the merbarone-functional analogues with better pharmacokinetic profile, structural similarity-based and property-based virtual screening was performed from ZINC database. After a logical and innovative virtual screening protocol, involving drug likeness evaluation, toxicity analysis, ADME descriptor evaluation, molecular docking and molecular dynamics simulations, sixteen molecules were identified as possible inhibitors of DNA cleavage step in the hTopoIIα-catalytic cycle. The identified compounds represent an interesting class of hits for hTopoIIα inhibitory potential. The availability of suitable structure of merbarone bound hTopoIIα shall have positive impact on the anti-cancer research using this target.
Tripathi, p. 17, col. 1;
Some of the compounds listed in Fig. 10 were previously evaluated for their in vitro biological activity (Table 5) by various research groups. ZINC10166606 was tested for cytotoxic potential against cancer cell lines and was found to be active, thus increasing the confidence on our developed pharmacoinformatics analysis strategy for the identification of anti-hTopoIIα potential of small molecules. ZINC09830193 was reported to exhibit anti-diuretic activity [60].
Id., p. 15, col. 2;
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Id., Fig. 10, p. 13.
While these compounds are tautomers of the compound of formula (I), one of ordinary skill in the art would recognize that the other tautomeric form exists in an equilibrium (the other tautomer is an inherent aspect of the compound). For example, Aly teaches that similar quinolones exist in tautomeric equilibrium:
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Aly, Fig. 1, p. 478.
Therefore, claims 9 and 18 were prima facie obvious at the time of filing.
Claims 22-23, 26-27, 37-43, 45, and 49 are dependent upon claim 9 and read on the compounds of Tripathi and are therefore prima facie obvious for the reasons given in the rejection of claim 9.
Claim(s) 9, 18, 22-23, 26-27, 30, 37-43, 45, and 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tripathi et al. (Journal of Molecular Graphics and Modelling, Volume 86, January 2019, Pages 1-18) (of record, IDS cite no. CE) as evidenced by Aly et al. (Molecular Diversity, Volume 24, p. 477–524, April 27, 2019), as applied to claims 9, 18, 22-23, 26-27, 37-43, 45, and 49 above, and further in view of McCurdy & Cohen (Bioisosterism, Drug Design Org, Feb. 2007, p. 1-138).
The rejection of claims 9, 18, 22-23, 26-27, 37-43, 45 and 49 above is incorporated herein by reference.
Claim 30 is directed towards the compound of claim 22. Wherein X1 is hydroxyalkyl. As shown in the rejection of claim 9, Tripathi teaches a compound of claim 22, wherein X1 is alkyl. While Tripathi does not teach a compound wherein X1 is hydroxyalkyl, one of ordinary skill in the art would have a reasonable expectation of success to substitute hydroxyalkyl for alkyl because it is commonly known in the art that hydroxy and CH3 are bioisosteres and as such a replacement of one for the other would produce a compound with similar properties.
For example, see the teachings of McCurdy:
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“Some examples of monovalent isosteres are illustrated in the following figure.”
McCurdy, p. 11-12.
Therefore, claim 30 was prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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