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 .
DETAILED ACTION
Election/Restrictions
Applicant's election with traverse that the absorptive excipient is hydroxy propyl methylcellulose, the strength-enhancing excipient is methacrylic acid-ethyl acrylate and the active ingredient is ibuprofen in response to the species election requirement, in the reply filed on 11 Apr 2024 is acknowledged. The traversal is on the ground(s) that claim 1 is generic and is not limited to the species listed above. This is not found persuasive because the applicant discloses alternative species for each of the genus’s which are not obvious variants of each other based on the current record.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-30 are under consideration to the extent of the elected species, i.e., that the absorptive excipient is hydroxy propyl methylcellulose, the strength-enhancing excipient is methacrylic acid-ethyl acrylate and the active ingredient is ibuprofen.
Specification
The disclosure is objected to because of the following informalities:
The brief description of the drawings for figures 3, 4, 6, 16, 17, 19, 20 and 40 do not contain a description for each part of the figure (e.g. a, b, c, etc.). See MPEP 608.01(f) which states “if the drawings show Figures 1A, 1B, and 1C and the brief description of the drawings refers only to Figure 1, the examiner should object to the brief description, and require applicant to provide a brief description of Figures 1A, 1B, and 1C.”
The brief description of the drawings for Figure 32 and 33 do not describe what is shown in the figures.
Appropriate correction is required.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: Figure 5 has reference number 520, Figure 6 has reference numbers 632 and 642 and Figure 15 has reference number 1510 which are not in the description. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) 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. 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.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: Reference number 1930 is in paragraph [00358] of the specification but not in the figures. 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. 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.
112b made below
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 1-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-28 and 30 are rejected for reciting “said strength-enhancing excipient” in claims 1 (line 11) and 30 (line 16) and "strength-enhancing excipient" in claims 2 and 23. There is insufficient antecedent basis for the limitations in the claims. Base claims 1 and 30 recite “at least one strength-enhancing polymeric constituent”, which encompasses multiple strength-enhancing polymeric constituents, and it is unclear whether “said strength-enhancing excipient” and “strength-enhancing excipient” includes just one, more than one, or all strength-enhancing polymeric constituents. Amending the claims to recite “the at least one strength-enhancing polymeric constituent” would overcome this rejection.
Claims 1-28 and 30 are rejected for reciting “said fluid-absorptive excipient” in claims 1 (line 13) and 30 (line 18) and "physiological fluid-absorptive…excipient" in claim 23. There is insufficient antecedent basis for the limitations in the claims. Base claim 1 recites “at least one physiological fluid-absorptive polymeric constituent” and base claim 30 recites “one or more fluid-absorptive polymeric constituents”, which encompasses multiple fluid-absorptive polymeric constituents, and it is unclear whether “said fluid-absorptive excipient” and “physiological fluid-absorptive…excipient” includes just one, more than one, or all physiological fluid-absorptive polymeric constituents. Amending the claims to recite “the at least one fluid-absorptive polymeric constituent” in claim 1 and “said one or more fluid-absorptive polymeric constituent” would overcome this rejection.
Claim 6 is rejected for its recitation of a “semi-solid mass” as it is not clear what this is intended to refer to. Claim 6 depends from claim 5 which recites that it is the frameworks that expands between 1.4 and 4 times its length and claim 1 recites a “semi-solid network” and a “viscous mass.” It is not clear if the “semi-solid mass” of claim 6 is the same as the “expanded framework” or if it refers to the “semi-solid network” or the “viscous mass” or if it refers to another part of the pharmaceutical dosage form.
Claim 21 recites “ethyl acrylate polymers (e.g., polymers including ethyl acrylate), methacrylate polymers (e.g., polymers including methacrylate).” The recitation of “(e.g., polymers including ethyl acrylate)” and “(e.g., polymers including methacrylate)” is unclear if what is in the parenthesis is restating the “ethyl acrylate polymers” and “methyacrylate polymers” or if they are further limitations of the recited “ethyl acrylate polymers” and “methyacrylate polymers.”
Claim 13 is unclear in its recitation of a “relevant physiological fluid.” The specification discloses that a “relevant physiological fluid’ is the physiological fluid surrounding the dosage form in the relevant physiological application ([00154]). As it is understood that the solubility in the strength-enhancing excipient will differ depending on the physiological fluid that the dosage form is applied to, there is not a clear limitation to the metes and bounds of the claims. For instance, if a strength-enhancing excipient met the solubility requirement in one fluid but not another, it is not clear if the claim would cover that particular strength-enhancing excipient or if it would be excluded from the claim.
Claim 23 recites “an element or framework.” It is unclear if this refers back to the “structural framework of one or more structural elements” as recited in claim one or to some other element and framework.
Claims 1-28 and 30 are rejected for reciting in claims 1 and 30 the limitation "said elements" (lines 5 and 7) as there is insufficient antecedent basis for this limitation in the claims. Base claims 1 and 30 recite “one or more structural elements”, which encompasses multiple structural elements, and it is unclear whether “said elements” includes just one, more than one, or all of the structural elements. Amending claims 1 and 30 to recite “said one or more structural elements” would overcome this rejection.
Claim 29 is rejected for reciting the limitation "said elements" as there is insufficient antecedent basis for this limitation in the claims. Claim 29 line 3 recites “one or more thin structural elements”, which encompasses multiple thin structural elements, and it is unclear whether “said elements” includes just one, more than one, or all thin structural elements. Amending the claim to recite “said one or more thin structural elements” would overcome this rejection.
Claim 2 recites “one or more structural elements” but doesn’t use said or the, rendering the claim unclear as to whether the recitation of “one or more structural elements” refers to the “one or more structural elements’ in claim 1 or if claim 2 refers to different structural elements. Amending the claim to recite “said one or more structural elements” would overcome this rejection.
Claim 4 recites “one or more said elements” which lacks antecedent basis and should recite “said one or more structural elements.”
Claim 29 recites “one or more said elements” which lacks antecedent basis and should recite “said one or more thin structural elements.”
Claim 3 recites “one or more free spaces” and it is unclear whether the recitation refers to the “one or more free spaces” in claim 1 or if it refers to different free spaces. Amending the claim to recite “said one or more free spaces” would overcome this rejection.
Claim 7 is rejected for reciting “one or more strength-enhancing excipients” in in the last line. There is insufficient antecedent basis for the limitation in the claim. Base claim 1 recites “at least one strength-enhancing polymeric constituent.” Amending claim 7 to recite “at least one strength-enhancing polymeric constituent” would overcome this rejection.
Claims 10-12 recite “at least one absorptive excipient.” It is unclear whether this refers to the “at least one physiological fluid-absorptive polymeric constituent” of claim 1 or if it refers to a different excipient. Amending the claims to recite “said at least one physiological fluid-absorptive polymeric constituent” consistent with claim 1 would overcome this rejection.
Claims 12 and 21 are indefinite for the recitation of “selected from the group comprising” before the Markush grouping. A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. See MPEP 2173.05(h).
Claims 13-16 recite “at least a strength-enhancing excipient” and claims 19-21 recite “at least one strength-enhancing excipient.” It is unclear if this is the “at least one strength-enhancing polymeric constituent” of claim 1 or if this a different strength-enhancing excipient. Amending the claims to recite “said at least one strength-enhancing polymeric constituent” would overcome this rejection.
Claim 17, recites “the one or more absorptive excipients” which lacks antecedent basis as claim 1 recites “at least one physiological fluid-absorptive polymeric constituent”. Amending the claim to recite “said at least one physiological fluid-absorptive polymeric constituent” would overcome this rejection.
Claim 18, recites “one or more strength-enhancing excipients” which lacks antecedent basis as claim 1 recites “at least one strength-enhancing polymeric constituent”. Amending the claim to recite “the at least one strength-enhancing polymeric constituent” would overcome this rejection.
Claims 17-18 and 22 recite “one or more elements” which is unclear as to whether this refers to the “one or more structural elements” of claim 1 or to different one or more elements. Amending the claims to recite “said one or more elements” would overcome this rejection.
Claim 24, recites “at least one free space” which lacks antecedent basis as claim 1 recites “one or more free spaces”. Amending the claim to recite “the one or more free spaces” would overcome this rejection.
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.
Claims 1-24 and 26-30 are rejected under 35 U.S.C. 103 as being unpatentable over Blaesi et al. (WO 2019/165106, published 29 August 2019, priority to 21 February 2018, referred to as Blaesi ‘106) as evidenced by the instant specification.
The applied reference has a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). Additionally, the current effective filing date of the instant application is 17 March 2021 and thus, WO2019/16516 published 29 August 2019 also qualifies as prior art under 35 U.S.C. 102(a)(1).
Use of the prior art under 35 U.S.C. 102(a)(2) as applied in the 35 U.S.C. 103 rejection below might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Blaesi ‘106 teaches a solid dosage form that comprises a drug-containing solid having an outer surface and an internal three dimensional structural framework of one or more thin structural elements where the framework is contiguous with and terminating at said outer surface and the structural elements comprise at least an active pharmaceutical ingredient and at least an absorptive polymeric excipient and at least a hydrophilic surface composition and that the structural elements further have segments spaced apart from adjoining segments defining free spaces wherein a plurality of adjacent free spaces combine across the drug containing solid to define one or more interconnected free spaces forming an open pore network and that when immersed in a physiological fluid the open pore network enables uniform wetting of the structural framework and the drug-containing solid transitions to a viscous medium, expanding in all dimensions ([0022]), rendering obvious instant claims 1, 3 and 4. Blaesi ‘106 teaches that the active may be ibuprofen ([00344]) and the at least one absorptive polymeric excipient may be hydroxypropyl methylcellulose or poly(methacrylic acid, ethyl acrylate) ([0056]), rendering obvious the fluid-absorptive polymeric constituent and the strength-enhancing polymeric constituent of the instant claims (claims 11, 12, 20, 21). As evidenced by the instant specification, methacrylic acid-ethyl acrylate copolymer has an elastic modulus of about 5.7 MPa, a tensile strength of about 1.8 MPa and a strain at fracture of about 3.5 ([00205]). As further evidenced by the instant specification, methacrylic acid-ethyl acrylate copolymer has a solubility in a fluid of pH no greater than 4 of at least 10 times smaller than the solubility in an fluid with a pH greater than 7 ([00355-00356]). Thus, the methacrylic acid-ethyl acrylate of Blaesi ‘106 renders obvious the parameters of instant claims 14-16, 19 and 30.
Regarding claims 2 and 7, Blaesi ‘106 teaches that the elements are bonded or connected to each other to form a continuous solid structure or three dimensional structure framework ([00127]), rendering obvious that the strength-enhancing excipient forms a substantially continuous or connected structure along the lengths of the one or more structural elements as recited.
Regarding claim 5, Blaesi ‘106 teaches that the solid expands to at least 1.4 times its initial volume ([0030]). Regarding claim 6, Blaesi ‘106 teaches that the structure expands as polymeric excipient and dissolution fluid interdiffuse until the pores close out and expansion of the viscous dosage form ceases and an expanded viscous mass is formed whereby the dosage form is retained in the stomach for a prolonged time and releases drug ([0020], [0021]), rendering obvious that the mass maintains its length as recited. Regarding claim 8, Blaesi ‘106 teaches that the thickness of the one or more elements is no greater than 2.5 mm, such as in the range of 1 μm – 1mm ([0037]). Regarding claim 9, Blaesi ‘106 teaches that the structural elements comprise a plurality of criss-crossed stacked layers of fibrous structural elements ([0046]). Regarding claims 10 and 13, Blaesi ‘106 teaches that the solubility of at least one absorptive polymeric excipient is greater than about 0.1 g/L or greater than 100 g/L (i.e. 100 mg/mL) in physiological fluid under physiological conditions ([00256]).
Blaesi ‘106 teaches example dosage forms such as
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(Figure 7) and teaches the fibers as a homogenous solid-solution of drug and excipient molecules ([0293]) rendering obvious the solid solution of claim 22. As the fibers are homogenous and the fibers are substantially the same throughout the figure, it is obvious that the segments have substantially the same weight fraction of physiological fluid-absorptive or strength-enhancing excipient distributed with the segments as recited in claim 23.
Blaesi ‘106 teaches that when forming the structures that air is used to evaporate the solvent and solidify the structures ([00293]). Thus, it is obvious that the free spaces of the structures would be filled with air. Blaesi ‘106 teaches that the dissolution fluid percolates into the free spaces ([00153]), rendering obvious that the free space is filled with matter that is removable by a physiological fluid under physiological conditions as in claim 24.
Regarding claims 17 and 18, Blaesi ‘106 teaches that the weight fraction of absorptive polymeric excipient is greater than 0.1 ([0060]).
Regarding claim 26, Blaesi ‘106 teaches the three dimensional structural framework has a tensile strength between 0.01 MPa and 100 MPa ([0066]).
Regarding the drug release of claims 27 and 29, Blaesi ‘106 teaches that eighty percent of the drug content is released in a time between 30 minutes and 72 hours ([0036]) rendering obvious the drug release over “prolonged time.” Regarding claim 28 Blaesi ‘106 teaches a dosage form that is a gastroretentive sustained release dosage form ([00337]).
Blaesi ‘106 does not expressly teach selecting the poly(methacrylic acid, ethyl acrylate), hydroxypropyl methylcellulose and ibuprofen as part of the dosage form with sufficient specificity to rise to the level of anticipation.
However, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have made a drug-containing solid having an outer surface and an internal structure contiguous with and terminating at said outer surface where the internal structure comprises a three dimensional structural framework of one or more two-dimensional elements and the two dimensional elements comprise at least one active ingredient and at least one excipient and comprise segments separated and spaced from adjoining segments by free spacings where the free spacings define one or more free spaces in the drug containing solid where the excipients are poly(methacrylic acid, ethyl acrylate) and hydroxypropyl methylcellulose and the active ingredient is ibuprofen. One of ordinary skill in the art would have been motivated to do so as the dosage forms are taught by Blaesi ‘106 and the excipients and active ingredient are taught as suitable components for the dosage forms. Thus, one of ordinary skill in the art would have a reasonable expectation of success in forming the dosage form with poly(methacrylic acid, ethyl acrylate) and hydroxypropyl methylcellulose excipients and with ibuprofen as each of these components are taught by Blaesi ‘106 and the modification of the prior art represents nothing more than the predictable use of prior art elements according to their established functions.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Blaesi et al. (WO 2019/165106, published 29 August 2019, priority to 21 February 2018, referred to as Blaesi ‘106) as evidenced by the instant specification as applied to claims 1-24 and 26-30 above and in view of Kanasty et al. (WO 2018/227147, published 13 December 2018) as evidenced by Xometry (Elastic Modulus: Definition, Values, and Examples).
The applied reference (Blaesi ‘106) has a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). Additionally, the current effective filing date of the instant application is 17 March 2021 and thus, WO2019/16516 published 29 August 2019 also qualifies as prior art under 35 U.S.C. 102(a)(1).
Use of the prior art under 35 U.S.C. 102(a)(2) as applied in the 35 U.S.C. 103 rejection below might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The teachings of Blaesi ‘106 are described supra.
Blaesi ‘106 does not teach that the elastic modulus is between 0.005 MPa – 15 MPa. This deficiency is made up for in the teachings of Kanasty.
Kanasty teaches gastric residence systems which expand to avoid passage through the pyloric sphincter and remain in the stomach for days to weeks and release drugs ([0003]-[0004]). Kanasty teaches various polymers for the gastric residences systems such as methacrylate esters (e.g. Eudragit RS) ([0119-0120]) and carrier polymers such as hydroxypropylmethyl cellulose ([0183-0184]). Kanasty teaches that the carrier polymers should have sufficient mechanical strength of Young’s modulus and tensile strength to avoid breaking in the stomach during the desired residence period ([0183]). As evidenced by Xometry, Young’s modulus is also known as elastic modulus (page 1). Thus, the mechanical properties such as Young’s modulus (elastic modulus) and tensile strength in the gastric dosage forms relate to how fast the dosage form will break down in the stomach and are art-recognized result effective variables.
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have used the pharmaceutical dosage form of Blaesi ‘106 as a gastroretentive dosage form where it retains its expanded size for a prolonged time in order to aid in sustained release of the drug. The dosage form of Blaesi ‘106 is known to expand and can be used for releasing a drug over an extended time, as taught by Blaesi ‘106. Thus, it would be obvious to one of ordinary skill to have the dosage form Blaesi ‘106 expand and maintain its form or a prolonged time in order to aid in sustained release of the drug. In light of the teachings of Kanasty that the mechanical properties of Young’s modulus and tensile strength relate to the rate of breakdown in the stomach, determining that the elastic modulus and tensile strength should be between 0.005 MPa-15MPa and 0.002 MPa and 15 MPa respectively would be a matter of optimization through routine experimentation. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In the instant case, one of ordinary skill could optimize the dosage form to have sufficient Young’s modulus (elastic modulus) so as to avoid premature breakdown of the dosage form before the desired release time frame.
Claims 1-4, 7-24 and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Blaesi et al. (US 2018/0303943, published 25 October 2018, referred to as Blaesi ‘943) as evidenced by the instant specification and evidenced by Vinchurkar et al. (Turk J Pharm Sci 2022;19(4):476-487).
Blaesi ‘943 teaches a pharmaceutical dosage form comprising a drug-containing solid having an outer surface and an internal structure contiguous with and terminating at said outer surface where the internal structure comprises a three dimensional structural framework of one or more two-dimensional elements and the two dimensional elements comprise at least one active ingredient and at least one excipient and comprise segments separated and spaced from adjoining segments by free spacings where the free spacings define one or more free spaces in the drug containing solid ([0007]). Blaesi ‘943 teaches that at least one excipient is absorptive of a physiological/body fluid ([0019]). Blaesi ‘943 teaches that at least one excipient transitions from solid to a fluidic or gel consistency solution upon contact with a volume of physiological/body fluid ([0021]), rendering obvious that an excipient forms a fluid-permeable, semi-solid network upon exposure to a physiological fluid as recited in claim 1. Blaesi ‘943 teaches that the use of excipients such as poly(methacrylic acid, ethyl acrylate) and hydroxypropyl methylcellulose ([0022]), rendering obvious the excipients of a strength-enhancing polymeric constituent and a fluid-absorptive polymeric constituent as recited in claims 1, 11, 12, 20, 21, 29 and 30. As evidenced by the instant specification, methacrylic acid-ethyl acrylate copolymer has an elastic modulus of about 5.7 MPa, a tensile strength of about 1.8 MPa and a strain at fracture of about 3.5 ([00205]). As further evidenced by the instant specification, methacrylic acid-ethyl acrylate copolymer has a solubility in a fluid of pH no greater than 4 of at least 10 times smaller than the solubility in a fluid with a pH greater than 7 ([00355-00356]). Thus, the methacrylic acid-ethyl acrylate of Blaesi ‘943 renders obvious the parameters of instant claims 14-16, 19 and 30. Blaesi ‘943 teaches that the dosage form structure may form a viscous mass after element swelling ([0091]), rendering obvious the fluid-absorptive excipient transitioning to a viscous mass as in claim 1. The element “swelling” as taught by Blaesi ‘943 further renders obvious the framework expanding along at least one dimension as recited in claims 1 and 30. Blaesi ‘943 teaches that the active ingredient may be ibuprofen ([0136]), rendering obvious the elected active ingredient species.
Regarding claims 2 and 7, Blaesi ‘943 teaches the dosage form may have a continuous two-dimensional element that makes up the three-dimensional structural framework ([0056], Fig 1e) rendering obvious a substantially continuous or connected structure along the lengths of one or more structural elements. Regarding claims 3, 4 and 7, Blaesi ‘943 teaches that the free spaces may be interconnected and that physiological fluid percolates into the interconnected free spaces ([0011], [0097], [0098]). Blaesi ‘943 teaches that the penetrated element is considered a gel ([0073], [0118]) and that diffusion of fluid may swell and spread the gel layer out ([0071], [0080], see Fig 3e) and that swelling of the excipient is a prerequisite for drug release from the two-dimensional element ([0062]), rendering obvious the framework expanding in all dimensions and transitioning said framework to a semi-solid mass releasing drug over time.
Regarding claim 8, Blaesi ‘943 teaches that the average thickness of the two-dimensional structural elements is no greater than 2.5 mm, such as between the range of 1 μm - 2.5 mm ([0103]). 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).
Regarding claim 9, Blaesi ‘943 teaches dosage forms such as shown in Fig 1 a and b which comprise criss-crossed stacked layers of fibers.
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As shown in the figure above, the segments in the dosage form are homogenous throughout the dosage form. Thus, it would have been obvious to have the segments with substantially the same weight fraction of physiological fluid-absorptive excipient or strength enhancing excipient distributed within the segment as recited in claim 23 and to have the excipients form a solid solution through the thickness of the one or more elements as recited in claim 22 in order to achieve an even distribution throughout the dosage form as taught by Blaesi.
Regarding claims 10, 13 and 30, Blaesi ‘943 teaches that the at least one excipient has a solubility greater than 100 g/L (i.e. 100 mg/mL) ([0112]), rendering obvious the solubility ranges of the instant claims. 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).
Regarding claims 17 and 18, Blaesi ‘943 teaches that the volume fraction of two-dimensional structural elements in the dosage form is in most cases in the range 0.1 – 0.9 ([0111]), rendering obvious the volume fraction ranges of the instant claims. Additionally, Blaesi ‘943 teaches that a small volume fraction of elements is desirable to fill small amounts of drug in a comparable large volume and that a large volume fraction of elements is desirable to fill large amounts of drug in a small volume ([0111]), thereby teaching that the volume fraction of the elements in the dosage form a result effective variable such that determining the best volume fraction for the elements in the dosage form for the best delivery of the active drug component would be a matter of routine optimization for one of ordinary skill. Thus, the claims are additionally obvious as a matter of routine optimization. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 24, Blaesi ‘943 teaches that the free space is filled with a matter that is partially or entirely removed upon contact with a physiological fluid under physiological conditions ([0023]). Regarding claim 27 and 29, Blaesi ‘943 teaches that the dosage form may contain another drug-containing solid that contains at least one active ingredient where 80 percent of the drug content is converted to dissolved molecules in a time greater than 60 minutes after immersion of the dosage form in a physiological fluid under physiological conditions ([0129]), thereby rendering obvious the 80 percent of drug content released within 1 hour to 30 days of claim 27 and the drug release over prolonged time of claim 29.
Regarding claim 28 and the recitation that the dosage form is gastroretentive, as evidenced by Vinchurkar, gastroretentive dosage forms release the drug in a controlled manner and provide a sustained and prolonged release of drugs in the stomach and intestine (page 484 right column). The dosage form of Blaesi ‘943 has predictable structure and drug release behavior ([0137]), may be used in physiological fluids such as stomach and gastrointestinal fluids ([0053]) and allows for a sustained release of drug content ([0129]). Thus, the dosage form of Blaesi ‘943 is understood to render obvious the gastroretentive form as recited in claim 28.
Blaesi ‘943 does not expressly teach selecting the poly(methacrylic acid, ethyl acrylate), hydroxypropyl methylcellulose and ibuprofen as part of the dosage form with sufficient specificity to rise to the level of anticipation.
However, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have made a drug-containing solid having an outer surface and an internal structure contiguous with and terminating at said outer surface where the internal structure comprises a three dimensional structural framework of one or more two-dimensional elements and the two dimensional elements comprise at least one active ingredient and at least one excipient and comprise segments separated and spaced from adjoining segments by free spacings where the free spacings define one or more free spaces in the drug containing solid where the excipients are poly(methacrylic acid, ethyl acrylate) and hydroxypropyl methylcellulose and the active ingredient is ibuprofen. One of ordinary skill in the art would have been motivated to do so as the dosage forms are taught by Blaesi ‘943 and the excipients and active ingredient are taught as suitable components for the dosage forms. Thus, one of ordinary skill in the art would have a reasonable expectation of success in forming the dosage form with poly(methacrylic acid, ethyl acrylate) and hydroxypropyl methylcellulose excipients and with ibuprofen as each of these components are taught by Blaesi ‘943 and the modification of the prior art represents nothing more than the predictable use of prior art elements according to their established functions.
Accordingly, the instant claims are rendered prima facie obvious over the teachings of Blaesi.
Claims 5, 6 and 25, 26 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Blaesi et al. (US 2018/0303943, published 25 October 2018, the referred to as Blaesi ‘943) as evidenced by the instant specification and evidenced by Vinchurkar et al. (Turk J Pharm Sci 2022;19(4):476-487) as applied to claims 1-4, 7-24 and 27-30 above and in view of Sandhu et al. (WO 2018/232413, published 20 Dec 2018) and Kanasty et al. (WO 2018/227147, published 13 December 2018) as evidenced by Xometry (Elastic Modulus: Definition, Values, and Examples).
The teachings of Blaesi are described supra.
Blaesi, while teaching the expanding dosage form as recited, does not teach that the dosage form expands to “a length between 1.3 and 4 times its length prior to exposure to said physiological fluid” (claim 5) or that it maintains its length for a prolonged time (claim 6) or the elastic modulus and tensile strength of the dosage form (claims 26 and 27). These deficiencies are rendered obvious in view of the teachings of Sandhu and Kanasty. Additionally, while the dosage form of Blaesi renders obvious “gastroretentive” as in claim 28, this is alternatively made obvious by the teachings of Sandhu.
Sandhu teaches a floating gastroretentive dosage form comprising a matrix core that is a sustained release swellable matrix core comprising an active agent, a superdisintegrant, a water-soluble polymer, an acid and a gas-generating agent and a membrane (page 3 lines 30-34). Sandhu teaches that gastroretentive dosage forms provide an improved pharmacokinetic profile by retaining the dosage form in the stomach for a prolonged period of time (page 8 lines 18-20, page 11 lines 16-20) and that the system maintains its integrity in the swollen state for a prolonged period of time (page 27 lines 3-5). Sandhu teaches that the dosage form swells at least about 200% (i.e. 3 times) in gastric fluid in about 30 minutes (page 4 lines 4-5) and swells to a size that prevents its passage through the pyloric sphincter (page 15 lines 3-5, page 22 lines 29-31). Sandhu teaches that swelling to a size that prevents its passage through the pyloric sphincter is an important factor in gastric retention of the system (page 22 line 33 – page 23 line 13). Sandhu teaches that dosage forms with a size of approximately 12-18 mm diameter in their expanded state are generally excluded from passage through the pyloric sphincter (page 23 lines 4-6).
Kanasty teaches gastric residence systems which expand to avoid passage through the pyloric sphincter and remain in the stomach for days to weeks and release drugs ([0003]-[0004]). Kanasty teaches various polymers for the gastric residences systems such as methacrylate esters (e.g. Eudragit RS) ([0119-0120]) and carrier polymers such as hydroxypropylmethyl cellulose ([0183-0184]). Kanasty teaches that the carrier polymers should have sufficient mechanical strength of Young’s modulus and tensile strength to avoid breaking in the stomach during the desired residence period ([0183]). As evidenced by Xometry, Young’s modulus is also known as elastic modulus (page 1). Thus, the mechanical properties such as Young’s modulus (elastic modulus) and tensile strength in the gastric dosage forms relate to how fast the dosage form will break down in the stomach and are art-recognized result effective variables.
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have used the pharmaceutical dosage form of Blaesi ‘943 as a gastroretentive dosage form where the dosage form expanded to a size of approximately 12-18 mm in diameter in order to avoid passage through the pyloric splincter and to have the dosage form retain its size for a prolonged time in order to aid in sustained release of the drug. Gastroretentive dosage forms that swell 200% (i.e. 3 times) for improved sustained release properties and to avoid passage through the pyloric splincter are known in the art as taught by Sandhu. The dosage form of Blaesi ‘943 is known to expand and can be used for releasing a drug over an extended time, as taught by Blaesi ‘943. Thus, it would be obvious to one of ordinary skill to have the dosage form Blaesi ‘943 expand to a size sufficient to avoid passage through the pyloric splincter and to maintain its form or a prolonged time in order to aid in sustained release of the drug and one would have a reasonable expectation of success as expandable dosage forms are known for use in such gastroretentive applications. Regarding the specific expansion of “1.3 to 4 times” as recited in claim 5, in view of the teachings of Sandhu that the dosage form should expand to between 12 – 18 mm so as to prevent passage through the pyloric splincter, the expansion of gastroretentive dosage forms is an art-recognized result effective variable such that determining that the expansion should be between 1.3 and 4 times would be a matter of optimization through routine experimentation. Similarly, in light of the teachings of Kanasty that the mechanical properties of Young’s modulus and tensile strength relate to the rate of breakdown in the stomach, determining that the elastic modulus and tensile strength should be between 0.005 MPa-15MPa and 0.002 MPa and 15 MPa respectively would be a matter of optimization through routine experimentation. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In the instant case, one of ordinary skill could optimize the expansion to between 1.3 and 4 times so as to achieve an appropriate dosage form size so as to avoid passage through the pyloric sphincter and to have sustained drug release. Additionally, it would be obvious to ensure the dosage form had sufficient Young’s modulus (elastic modulus) and tensile strength so as to avoid premature breakdown of the dosage form before the desired release time frame.
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 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 11,129,798 in view of Blaesi et al. (US 2018/0303943, published 25 October 2018, referred to as Blaesi ‘943) as evidenced by the instant specification and evidenced by Vinchurkar et al. (Turk J Pharm Sci 2022;19(4):476-487) and in view of Sandhu et al. (WO 2018/232413, published 20 Dec 2018) and Kanasty et al. (WO 2018/227147, published 13 December 2018) as evidenced by Xometry (Elastic Modulus: Definition, Values, and Examples).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-38 of the ‘798 patent render instant claims 1-30 obvious.
The ‘798 patent recites a pharmaceutical dosage from comprising a drug-containing solid having an outer surface and an internal three-dimensional fiber network structure contiguous with and terminating at said outer surface. The fibers comprise at least one active ingredient and at least one excipient that has a solubility greater than 1 g/L (1 mg/mL). The fiber thickness is between 1.7 μm to 2.5 mm. The fibers comprise free spacings defining at least an interconnected free space terminating at said outer surface and filled with at least a gas (claim 1). At least one excipient is absorptive of physiological/body fluid (claims 14-15). At least one excipient transitions from solid to a gel consistency upon contact with body fluid (claim 16). The excipient is hydroxypropyle methyl cellulose and poly(methacrylic acid, ethyl acrylate) (claims 17, 18). The gas or other matter in the free space is removed upon contact with body fluid (claim 19). The fibers are stacked in a cross-ply arrangement (claim 25). Additional claims are more specific than the instant claims and render the instant claims obvious.
The ‘798 patent does not recite the drug ibuprofen or that the dosage form expands (claims 5, 6), the fraction of the absorptive and strength enhancing excipients (claims 17 and 18), the elastic modulus and tensile strength (claims 25 and 26) or the prolonged release of the drug (claims 27 and 28). These deficiencies are made up for in the teachings of Blaesi, Sandhu and Kanasty.
The teachings of Blaesi, Sandhu and Kanasty are described supra.
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have formed the dosage form of the ‘798 patent as a gastroretentive dosage form that expands and releases drug over an extended period. Forming a drug-containing solid comprising an outer surface and an internal three dimensional structural framework and comprises poly(methacrylic acid, ethyl acrylate) and hydroxypropyl methylcellulose and ibuprofen as the drug where the dosage form expands in body fluid is known based on the teachings of Blaesi. Using an expanding dosage form as a gastroretentive dosage and allowing the dosage form to expand so that it does not pass through the pyloric sphincter so as to allow for sustained drug release is known from Sandhu and the mechanical properties of Young’s modulus (elastic modulus) and tensile strength are result effective variables known to relate to how fast the dosage form will break down in the stomach for which one of ordinary skill would be motivated to determine the appropriate mechanical properties for drug release during the intended time frame.
Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. 11,865,216 in view of Blaesi et al. (US 2018/0303943, published 25 October 2018, referred to as Blaesi ‘943) as evidenced by the instant specification and evidenced by Vinchurkar et al. (Turk J Pharm Sci 2022;19(4):476-487) and in view of Sandhu et al. (WO 2018/232413, published 20 Dec 2018) and Kanasty et al. (WO 2018/227147, published 13 December 2018) as evidenced by Xometry (Elastic Modulus: Definition, Values, and Examples).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-37 of the ‘216 patent render instant claims 1-30 obvious.
The ‘216 patent recites a pharmaceutical dosage from comprising a drug-containing solid having an outer surface and an internal three-dimensional structure of thi