Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restriction
Amended claims 1, 52-69, 74-78, 83, 84-89, 91, 93, 97, 99-101, 105, 106, 108-110, 115, 118, 121 124 & 164-166 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Applicant elected a composition comprising the compound of formula (I) and excipients. Claims 1, 52-69, 74-78, 83, 84-89, 91, 93, 97, 99-101, 105, 106, 108-110, 115, 118, 121 & 124 are now directed to method of using compositions comprising the compound of formula (I) and excipients. Had these claims been originally been presented, they would have been restricted. New claims 149, 153-156 & 160-162 are drawn to previously unelected embodiments of composition.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 1, 52-69, 74-78, 83, 84-89, 91, 93, 97, 99-101, 105, 106, 108-110, 115, 118, 121, 124 149, 153-156, 160-162 & 164-166 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Status
Applicant’s claim amendments and arguments in the response filed 04 August 2025 is acknowledged.
Claims 1, 52-69, 74-78, 83-89, 91, 93, 97, 99-101, 105, 106, 108-110, 115, 118, 121, 124, 127-132, 135, 137-142 & 144-166 are pending.
Claims 148-166 are new.
Claims 2-51, 70-73, 79-82, 90, 92, 94-96, 98, 102-104, 107, 111-114, 116, 117, 119, 120, 122, 123, 125, 126, 133, 134, 136 & 143 are cancelled.
Claims 1, 52-69, 74-78, 83-89, 91, 93, 97, 99- 101, 105, 106, 108-110, 115, 118, 121, 124, 127, 128, 137, 138, 146 & 147 are amended.
Claims 1, 52-69, 74-78, 83-89, 91, 93, 97, 99-101, 105, 106, 108-110, 115, 118, 121, 124, 129, 130, 149, 153-156, 160-162 & 164-166 are withdrawn.
Claims 127, 128, 131, 132, 135, 137-142, 144-148, 150-152, 157-159 & 163 are under consideration.
Examination is to the extent of the following species:
Formulation F2 in Table 1 consisting of:
(i) 10.0% w/w (30 mg) of micronized 2-(3,5-dichloro-1-oxido-pyridine-4-yl)-1-(7- difluoromethoxy-2',3',5',6'-tetrahydro-spiro[1,3-benzodioxole-2,4-(4H)- thiopyran-1',1'-dioxide]-4-yl)ethanone,
(ii) 17.5% w/w hydroxypropylmethylcellulose (HPMC);
(iii) 71.0% lactose monohydrate, 0.5% w/w colloidal silicon dioxide, and 1.0% w/w
magnesium stearate; and a pharmaceutically acceptable coating system, wherein the pharmaceutically acceptable coating system is a polyvinyl alcohol (PVA)-based coating system, wherein the coating system adds 4% w/w.
Priority
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file. The effective filing date of the instant application is 01/15/2019. The foreign priority document is in the English language.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04 August 2025 has been fully considered by the examiner. A signed and initialed copy of each IDS is included with the instant Office Action.
Withdrawn Objections/Rejections
The objection to claim 94 is withdrawn due to cancellation of the claim.
The objection to claim 146 is withdrawn because it is now written in parallel to the rest of the claim listing.
The rejection of claims 104 under 35 USC 112(b) and 35 USC 103 (a) is withdrawn due to cancellation of the claims.
The rejection of claims 1, 105, 106, 115, 118, 127, 146 & 147 under 35 USC 112(b) is withdrawn due to amendments which remove parenthetical expressions.
The rejection of claims 77 & 78 is withdrawn under 35 USC 112(b) due to amendments which recite “the one or more filler is …”
The rejection of claims 128, 137 & 138 under 35 USC 112(b) is withdrawn due to amendments which recite “one or more pharmaceutically acceptable filler”.
The rejection of claims 1, 58, 59, 62-64, 67-69, 74-78, 83-89, 104-106, 108 & 109 under 35 U.S.C. 103 as being unpatentable over Simon, Cheung and Sedmak; claims 52 & 56 as unpatentable over Simon, Cheung, and Sedmak and further in view of Dahl; claims 53-55 & 57 as unpatentable over Simon, Cheung, Sedmak and Dahl and further in view of Chaumeil; claims 65 & 66 as unpatentable over Simon, Cheung and Sedmak and further in view of Dow; claims 91 & 93 as being unpatentable over Simon, Cheung and Sedmak and further Teckoe; and claims 99-101, 115 & 118 as being unpatentable over Simon, Cheung, Sedmak and Teckoe and further in view of Chaumeil is withdrawn due to Applicant amendments to recite a method of using a modified release tablet formulation comprising the compound of formula (I) and excipients.
New & Maintained Objections/Rejections
Claim Objections
Claims 127, 146, 147, 150-152, 157-159, & 163 are objected to because of the following informalities:
Claims 127, 146 & 147 are not 37 CFR 1.121 compliant. The claims admix double braces and strike throughs for deletions. This is improper. Deletion of characters may be denoted by double braces or a strike through but not both. Claim 126 also admixes one set of braces and a strikethrough to denote a deletion (i.e. “[
If claims 1, 105, 106, 110, 115, 118, 121 & 124 were under examination they would also be rejected under 37 CFR 1.121.
Claims 150-152, 157-159 & 163 use the colloquial term for hydroxypropylmethyl cellulose (i.e. hypromellose). Claims 150-152, 157-159 & 163 ultimately depend from claim 127 which recites “hydroxypropyl methylcellulose” and not hypromellose. Applicant may wish to consider an amendment to claims 150-152, 157-159 & 163 to recite “hydroxypropyl methylcellulose” to keep the claim language consistent through the claim listing.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 151, 152, 158 & 159 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 151 recites the limitation "the PVA-based coating system" in the last line. There is insufficient antecedent basis for this limitation in the claim.
Claim 152 recites the limitation "the PVA-based coating system" in the last line. There is insufficient antecedent basis for this limitation in the claim.
Claim 158 recites the limitation "the PVA-based coating system" in the last line. There is insufficient antecedent basis for this limitation in the claim.
Claim 159 recites the limitation "the PVA-based coating system" in the last line. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 127, 128, 131, 132, 137-142, 146, 147 & 148 are rejected under 35 U.S.C. 103 as being unpatentable over Simon (US 2015/0111915; Published: 04/23/2015; IDS 11/13/2023; previously cited), Cheung (WO 2012/016280; Published: 02/09/2012; previously cited) and Sedmak (EP 2266541; Published 12/29/2010; previously cited).
With regard to claims 127 (i) & 148, Simon in Example 8 teaches the phosphodiesterase 4 (PDE4) inhibitor:
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for the treatment of inflammatory diseases and disorders (abstract; [0130]). Simon teaches his compound and composition is for treating inflammatory diseases and disorders including asthma, rhinitis, and arthritis (abstract; Simon’s claim 1). With regard to claims 127 (ii), 127 (iii), 127 (iv) 132, 137, 139 & 148, Simon teaches the PDE 4 inhibitors of their invention may be in in the form of a compressed tablet having been mixed with a binder which may be lactose, hydroxypropyl methylcellulose (HPMC) and a lubricant which may be magnesium stearate [0067]. With regard to claims 128(a), 131 & 148, Simon teaches of their invention “In general a single dose will be in the range from 0.01 to 400 mg/kg body weight. The compound may be administered as a bolus (i.e. the entire daily dose is administered at once) or in divided doses two or more times a day”. The average adult weights about 60 kg so Simon teaches doses ranging from 6mg to 2,400mg (claims 128 (a) & 131).
Simon does not teach the modified release, the lactose is lactose monohydrate, and inclusion of colloidal silicon dioxide.
Cheung teaches angina, asthma and COPD are inflammatory diseases [0066].
With regard to claims 127 & 148, Sedmak teaches a formulation for treating angina [0002]. Sedmak teaches an immediate release tablet [0009]. With regard to claims 127(ii), 132 & 148, and the elected species, Sedmak teaches ”[t]he composition preferably comprises 0.5 to 40 wt.-%, particularly 1 to 20 wt.-%... of a binder” which may be hydroxypropylmethylcellulose ([0019] & [0021]). With regard to claims 128(b), 132, 137, 138 & 148, and the elected species, Sedmak teaches the tablet “preferably comprises 20 to 99 wt.-%, particularly 50 to 95 wt.-%, more preferably 70 to 90 wt.-%, most preferably 80 to 90 wt.-% of filler. According to another embodiment, the composition comprises 20 to 99 wt.-%, particularly 30 to 90 wt.-%, more preferably 40 to 70 wt.-%..” which may be lactose monohydrate (i.e. about 71% lactose monohydrate; [0014]-[0015]]). With regard to claims 127(iv) & 148, Sedmak teaches “suitable glidants include colloidal silicon dioxide … The composition preferably comprises 0.1 to 10 wt.-%, particularly 0.25 to 5 wt.-%, and more preferably 0.5 to 2 wt.-% of glidant” [0025]. With regard to claims 85 & 86 , Sedmak teaches “ Suitable lubricants include… magnesium stearate… magnesium stearate…are particularly preferred. The composition preferably comprises 0.1 to 10 wt.-%, particularly 0.25 to 5 wt.%, and more preferably 0.5 to 2 wt.-% of lubricant” [0024]. With regard to claims 140-142, Sedmak teaches film coating “can be used to provide for improved surface smoothness and color, increased chemical and physical stability of the active agent due to reduced permeability for gases such as oxygen and/or water vapor, less disintegration of the solid composition in acidic medium resulting in decreased gastrointestinal side effects, and easier swallowing of tablet” [0032]. With regard to claims 140-142, Sedmak teaches the coating can be polyvinyl alcohol (Kollicoat IR) [0032]. With regard to the release profile recited by claims 127, 146 & 147, Sedmak teaches “ [0033] According to one embodiment, the composition according to the invention exhibits a release profile characterized in that at least 40 %, particularly at least 50 %, more preferably at least 60 %, most preferably at least 70 % by weight of the active agent are released within a period of 30 minutes under non-sink conditions (USP paddle, 75 rpm, 900 ml acetate buffer pH 4.5)” [0033].
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel
Here at least rationale (B) may be applied in which it would have been prima facie obvious to the ordinary skilled artisan at the time of filing to have substituted Simon’s generically taught tablet vehicle with the tablet vehicle taught by Sedmak because Simon’s formulation is for treating inflammatory diseases and Sedmak’s tablet vehicle is used to treat the inflammatory diseases. Asthma and angina inflammatory diseases as taught by Cheung so it would have been obvious to the ordinary skilled artisan to use a tablet vehicle that treats one inflammatory disease for a related inflammatory disease. The ordinary skilled artisan would have been motivated to do so, with an expectation of success, in order to supply an immediate release tablet it rapidly treat asthma.
With regard to the recited amounts lactose monohydrate/pharmaceutically acceptable filler, HPMC/hydrophilic matrix former, colloidal silicon dioxide/glidant and magnesium stearate/lubricant, and dose of the compound, the combined teachings of Simon, Cheung and Sedmak teach these parameters with values that fall inside of the claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Claims 135 & 163 are rejected under 35 U.S.C. 103 as being unpatentable over Simon, Cheung and Sedmak as applied to claims 127, 128, 131-134, 137-142, 146, 147 & 148 above, and further Dow (Published: 07/2000; previously cited).
The teachings of Simon, Cheung and Sedmak are described above. In brief, the prior art teachings suggest an immediate release tablet comprising HPMC.
Neither Simon, Cheung nor Sedmak teach the HPMC is hypromellose 2208/Methocel K100 LV.
In the same field of invention of tablets, Dow teaches hypromellose 2208/Methocel K100 LV had the highest drug release weight of the 4 examined grades of HPMC (pg. 20)
Here, at least rationale (B) may be employed in which would have been prima facie obvious to the ordinary skilled artisan to substitute the HPMC of the tablet suggested by the combined teachings of Simon, Cheung and Sedmak with hypromellose 2208/Methocel K100 LV as suggested by Dow in order to increase the drug release rate from the tablet. The ordinary skilled artisan would have been motivated to do so, with an expectation of success, because the tablet suggested by the prior art is an immediate release tablet and hypromellose 2208/Methocel K100 LV provides rapid drug release. It would be obvious to it for the same purpose of immediately releasing the drug.
Claims 144 & 145 are rejected under 35 U.S.C. 103 as being unpatentable over Simon, Cheung and Sedmak as applied to claims 127, 128, 131-134, 137-142, 146, 147 & 148 above, and further Teckoe (Published: 06/2013; previously cited).
The teachings of Simon, Cheung and Sedmak are described above. In brief, the combined teachings of Simon, Cheung and Sedmak suggest an immediate release PVA-film coated tablet consisting of recited compound, lactose monohydrate, HPMC, colloidal silicon dioxide, and magnesium stearate.
Neither Simon, Cheung nor Sedmak teach the weight gain of the PVA film on the tablet.
In the same field of immediate release compositions, Teckoe teaches immediate release film coating provides many significant advantages (pg. 531). Teckoe found a 4% weight gain of Opadry 200 (a PVA tablet coating system) on an immediate release tablet produced results which were “the color standard” with excellent color uniformity (pg. 533, 534 & 535) . The coated tablets disintegrated in 300 seconds with low variability (Figure 9; pg. 537).
Here, at least rationale (G) may be applied in which would have been prima facie obvious to the ordinary skilled artisan at the time of filing to have modified the immediate release tablet suggested by the combined teachings of Simon Cheung and Sedmak by adjusting the weight gain of the PVA film coating to be 4% by weight of the tablet as taught by Teckoe because this amount of PVA-coating is used for immediate release tablets as taught by Teckoe and it is obvious to modify similar compositions in the same way. The ordinary skilled artisan would have been motivated to do so, with an expectation of success in order to provide tablets with a film that rapidly dissolves within about 300 seconds with low variability as taught by Teckoe.
With regard to the PVA-alcohol coating weight gain, the combined teachings of Simon, Cheung, Sedmak and Teckoe teach this parameter with a value that fall inside of the claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Claims 150-152 & 157-159 are rejected under 35 U.S.C. 103 as being unpatentable over Simon, Cheung, Sedmak and Teckoe, as applied to claims 127, 128, 131-134, 137-142 & 144-148 above, and further in view of Chaumeil (Published 1998; previously cited).
Claim Interpretation: Claims 150 & 157 are interpreted as the optional PVA-based coating system as being present based upon Applicant’s elected species.
The teachings of Simon, Cheung, Sedmak and Teckoe are described above. In brief, with regard to claims 152 & 159, Simon, Cheung, Sedmak and Teckoe teach a tablet comprising 6mg to 2,400mg of compound of formula (I) (Simon’s compound 108). With regard to claims 150-152 & 157-159, Simon teaches “conveniently, the active ingredient comprises from 0.05-99.9% by weight of the formulation” [0056]. Further, Sedmak teaches “a) 0.1 to 60 wt.-%, particularly 0.5 to 40 wt.-%, more preferably 1 to 20 wt.-%, and most preferably 5 to 15 wt.% of rivaroxaban or a pharmaceutically acceptable salt or solvate thereof” and in Tablets 7A-7B teaches the active agent in an amount of 10% of the tablet formulation in a tablet comprising aerosil 200 (colloidal silicon dioxide) and magnesium stearate [0065]. As such, the ordinary skilled artisan would have been motivated to use 10 %w/w of Simon’s compound 108/compound of formula (I) as a place in which to start routine optimization. With regard to claims 150-152 & 157-159, the combined teachings of Simon, Cheung, Sedmak and Teckoe teach a tablet vehicle consisting of the active agent, hypromellose/HPMC/hydrophilic matrix former, lactose monohydrate/filler, colloidal silicon dioxide/glidant, and magnesium stearate/lubricant in overlapping amounts and a PVA-based coating system to a weight gain of 4%. Simon teaches optimization of their pharmaceutical ingredient to achieve a particular and appropriate rate of absorption by teaching “when the active ingredient is administered in the form of salts with pharmaceutically acceptable non-toxic acids or bases, preferred salts are for instance easily water soluble or slightly soluble in water, in order to obtain a particular and appropriate rate of absorption” [0077].
Neither Simon, Cheung, Sedmak, nor Teckoe teach micronization of 2-(3,5-dichloro-1-oxido- pyridine-4-yl)-1-(7-difluoromethoxy-2',3',5',6' -tetrahydro-spiro[ 1,3 - benzodioxole-2,4'-(4H)-thiopyran-1',1'-dioxide]-4-yl)ethanone.
Chaumeil teaches “the smaller the particles, the higher the rate of dissolution” (pg. 212). Chaumeil in Figure 4 teaches micronized diosmin had 72% intestinal absorption compared to nonmicronized which only had 17% absorption (pg. 214). Chaumeil teaches griseofulivin is a poorly soluble drug that was micronized to a median particle size of 3 micrometers (pg. 213).
Here at least rationale (G) may be applied in which it would have been prima facie obvious to the ordinary skilled artisan at the time of filing to have modified the particle size of 2-(3,5-dichloro-1-oxido- pyridine-4-yl)-1-(7-difluoromethoxy-2',3',5',6' -tetrahydro-spiro[ 1,3 - benzodioxole-2,4'-(4H)-thiopyran-1',1'-dioxide]-4-yl)ethanone to micronize it to a size of 3 microns in order to increase its dissolution and intestinal absorption as suggested by Chaumeil. The ordinary skilled artisan would have been motivated to do so, with an expectation of success, in order to improve the absorption of the drug and its bioavailability.
With regard to the recited size of the compound, the combined teachings of Simon, Cheung, Sedmak, Teckoe and Chaumeil suggest this parameter in a size that falls within the claimed range.
Response to Arguments
Applicant argues method claim 1 avoids the undesirable gastrointestinal side effects associated with all PDE4 inhibitor compounds while still providing high systemic exposure (reply, pg. 27-30). Applicant argues Simon does not recognize any negative side effects for the compound of formula (I) so there is no motivation to formulate the compound in any particular way (reply, pg. 28). Applicant argues it is not obvious to combine Simon with Sedmak because the Huang reference filed by Applicant on an IDS teaches PDE4 inhibitors are very bioavailable, resulting in severe gastrointestinal side effects while Sedmak’s rivaroxaban has poor oral bioavailability and the goal of Sedmak’s tablet formulation is to increase bioavailability (reply, pg. 29-30).
Applicant’s arguments pertaining to claim 1 are not persuasive because Applicant’s arguments are drawn to an unelected an unexamined invention. Applicant claim amendments on 04 August 2025 introduced an invention shift from a composition claim to a method claim. The general policy of the Office is that applicants are not permitted to shift to claim another invention after an election is made and an Office action on the merits is made on the elected invention (see MPEP 819).
With regard to the arguing of Simon and Sedmak individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Simon teaches their inventive compounds are for treatment of inflammatory diseases and disorders and the compound may be included in a tablet. Cheung teaches angina is an inflammatory disease. It would have been prima facie obvious to the ordinary skilled artisan at the time of filing to have substituted Simon’s generically taught tablet vehicle with the tablet vehicle taught by Sedmak because Simon’s formulation is for treating inflammatory diseases and Sedmak’s tablet vehicle is used in the treatment of the inflammatory diseases. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991) (discussed below).
Applicant argues the composition of claim 127 shows unexpected results with the range of about 15 to about 25 w/w% HPMC fully supported by the Examples in the present application and in particular, tablet F2 of the declaration filed on 26 December 2024 (reply, pg. 31-34). Applicant argues if different grades of HPMC are used the same or similar results would be expected (reply, pg. 32).
This is not persuasive. “MR New Tablet”/F2 tablet is a specific formulation with specific reagents in specific amounts. However, independent claim 127 is generic to the amounts of reagents including the compound of formula (I), the pharmaceutically acceptable filler and pharmaceutical excipients and the particle size of the drug. Claim 127 is also generic to the type of hypromellose/HPMC. This is important because HPMC comes in different molecular weights/grades with varying viscosities. Low molecular weight HPMC is typically associated with fast dissolution and heavier molecular weight HPMC is typically associated with greater viscosity and slower dissolution. The examiner notes that “MR New Tablet”/F2 tablet used HPMC Methocel K100LV which Pubchem states is synonymous with Hypromellose 2208. Further comparison of the instant claims to the “MR New Tablet”/F2 tablet shows the “MR New Tablet”/F2 tablet comprised a 4% gain of a PVA-based film coating. However, claim 127 does not recite a PVA film.
"[O]bjective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).
With Applicant’s assertion that different grades of HPMC are expected to provide similar or the same effects, these are Attorney’s arguments. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)
Applicant argues claims 127 and 137 require specific dissolution profiles (reply, pg. 31-32).
This is not persuasive. The combined teachings of Simon, Cheung and Sedmak teach the recited reagents in the recited amounts. In particular, Sedmak teaches HPMC in an amount of particularly 1 to 20 wt.-% . As such the composition suggested by the combined teachings of Simon, Cheung and Sedmak necessarily have the recited dissolution profile. The US Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent Applicant may present previously unmeasured characteristics. When PTO shows a sound basis for believing that the products of the Applicant and the prior art are the same, the Applicant has the burden of showing that they are not. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Applicant reiterates their argument that a different modified release formulation ,“MR1” is the closest prior art; not Sedmak’s tablet (reply, pg. 33). Applicant further argues that the MR1 formulation is a capsule and not a tablet is irrelevant because the slow rate of drug release results in a low systemic exposure (reply, pg. 35).
Again, this is not persuasive. Applicant is presenting arguments to an unclaimed invention. The MR 1 formulation is a hard capsule (see Declaration-pg. 6). This is an apples-to-oranges comparison and is not a comparison with the dissolution profile of the closet prior art which is Sedmak.
An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). "A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference." In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential). Notably, Applicant has not explained their deviation from Sedmak.
Applicant argues Sedmak was published in German but was also published as US Publication No. 2015/037415 to Benke, with Benke showing more than 92% of the rivaroxaban was released in 30 minutes (reply, pg. 33-34). Applicant argues this is comparable to their comparative IR tablet in Figure A (reply, pg. 35). Applicant further argues the sink versus non-sink conditions described in Sedmak (reply, pg. 36).
This is not persuasive. Applicant is arguing references not of record and not used in the rejection. This confuses the record. Sedmak is EP 2266541 and was published in English. Sedmak shows no such Table as that shown by Benke in Table 1. Further, the conditions in which dissolution occurred as recited by Applicant and as taught by Sedmak are different. The examiner again reiterates the US Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent Applicant may present previously unmeasured characteristics. When PTO shows a sound basis for believing that the products of the Applicant and the prior art are the same, the Applicant has the burden of showing that they are not. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). In the instant case, Simon teaches the recited active agent to treat inflammation in a tablet. Sedmak teaches a tablet/vehicle for treating inflammation which has the recited excipients in amounts which overlap with the claimed ranges. As such, the tablet suggested by the combined teachings of Simon, Cheung and Sedmak necessarily have the recited dissolution profile because "Products of identical chemical composition can not have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Applicant argues they have found the “Goldilocks” zone in which a unique dissolution profile inhibits the release of the compound of formula (I) just enough to minimize the undesirable side effects but not too much to reduce systemic absorption (reply, pg. 36).
This is not persuasive. As discussed above, the combined teachings of Simon, Cheung and Sedmak teach a tablet with the recited active agent and excipients in an amounts which overlap with the claimed ranges. The tablet suggested by the combined prior art teachings would also have this “Goldilock’s” zone. The Federal Circuit concluded that “[g]ood science and useful contributions do not necessarily result in patentability.” Id. at 1364, 83 USPQ2d at 1304.(MPEP 2145).
Applicant argues Chaumeil, Dow and Teckoe do not cure the deficiencies of Simon, Cheung and Sedmak (reply, pg. 37-38).
This is not persuasive. Discussion as to how the teachings of Simon, Cheung and Sedmak render at least claim 127 as obvious is addressed above. Chaumeil teaches micronization of the active agent improves dissolution of active agents and their bioavailability. Dow teaches in the tableting field hypromellose 2208/Methocel K100 LV had the highest drug release weight of the 4 examined grades of HPMC (pg. 20). Teckoe found a 4% weight gain of Opadry 200 (a PVA tablet coating system) on an immediate release tablet produced results which were “the color standard” with excellent color uniformity (pg. 533, 534 & 535) . The coated tablets disintegrated in 300 seconds with low variability (Figure 9; pg. 537). The features taught by Chaumeil, Dow and Teckoe are important in formulating highly bioavailable formulations.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LORI K MATTISON whose telephone number is (571)270-5866. The examiner can normally be reached 9-7 (M-F).
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/LORI K MATTISON/ Examiner, Art Unit 1619
/NICOLE P BABSON/ Primary Examiner, Art Unit 1619