DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Note: Change in Examiner, Art Unit and SPE
The Examiner of record is now Genevieve Alley, Art Unit 1617. Therefore, future correspondence should reflect such changes. Also, at the end of the Action is the information regarding the SPE and the Art Unit.
Status of Claims
A new claim set was filed on 5/22/26 with the following:
Amended claims
1-4, 14, 22 and 25
Newly canceled claims
5
Newly added claims
Previously canceled claims
6-7
Previously withdrawn claims
27-55
Claims under instant examination
1-4 and 8-26
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/22/26 has been entered.
Withdrawn Claim Rejections
All rejections pertaining to claim 5 are moot because the claim was cancelled in view of the amendments filed on 5/22/26.
The rejections of:
claims 1-5, 8-23 and 25 under 35 U.S.C. 103 as being unpatentable over US 11602507 to Guditi, in view of WO 91/13612 to Grattan (cited on IDS dated 8/21/23), Singh et al (FABAD J. Pharm. Sci., 32, 91-100), US 6193962 to Metcalf et al., and US 5296228 to Chang; and
claims 1-5 and 8-26 under 35 U.S.C. 103 as being unpatentable over US 20130034503 to Howard et al (Howard) in view of US 11602507 to Guditi, WO 91/13612 to Grattan, Singh et al (FABAD J. Pharm. Sci., 32, 91-100), US 6193962 to Metcalf et al., and US 5296228 to Chang
are hereby withdrawn in response to the Applicants arguments and amendments filed on 5/22/26.
New Claim Objections
Claim 22 is objected to because of the following informalities: the claim recites “codeine” twice in the Markush grouping (lines 5 and 14).
Appropriate correction is required.
New Claim Rejections - 35 USC § 112(a), Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claim 3 is rejected under 35 U.S.C. §112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter that was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. Applicants are directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112 ¶1 "Written Description" Requirement, Rev. 1, 2008; at http://www.uspto.gov/web/menu/written.pdf.
The claim broadly embraces a pharmaceutical composition for oral administration comprising micronized ion-exchange resin particles, at least one therapeutic agent and “a solvent-soluble material selected from the group of solvent-soluble polymers, lipophilic surfactants, phospholipids, fatty acids, polyvinyl pyrrolidone, phosphatidylcholine, phosphatidylethanolamine, stearic acid, oleic acid, or combinations thereof”, necessitating structure/function relationships.
The specification does not disclose any solvents that the abovementioned Markush group needs to be soluble in, with the scope of claim 3 having the required activities. However, in the absence of the compounds being used, the artisan would not have accepted that applicant was in possession of the claimed method of use. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See, e.g., In re Wilder, 22 USPQ 369, 372-3 (Fed. Cir. 1984). (Holding that a claim was not adequately described because the specification did 'little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.') Mere indistinct terms (such as known classes of compounds which are now claimed based on a limited functional capability, such as “an ophthalmic agent” however, may not suffice to meet the written description requirement. This is particularly true when known compound classes, which otherwise meet the written description requirement, are limited to a smaller subgroup claimed in purely functional terms, such as the case in the instant claims. See Univ. of Rochester v. G.D. Searle, 69USPQ2d 1886 (CAFC 2004) at 1892, stating: The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. A description of an antiinflammatory steroid, i.e., a steroid (a generic structural term) described even in terms of its functioning of lessening inflammation of tissues fails to distinguish any steroid from others having the same activity or function. A description of what a material does, rather than of what it is, usually does not suffice. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. (Emphasis added). Conversely, a description of a chemical genus will usually comprise a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. See Univ. of Calf. V. Eli Lilly, 43 USPQ 2d 1398, 1406 (Fed. Cir. 1997). This is analogous to enablement of a genus under Section 112, l[ 1, by showing the enablement of a representative number of species within the genus. A chemical genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has substantial variance, the disclosure must describe a sufficient number of species to reflect the variation within that genus. See MPEP §2163. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. MPEP §2163. Here, the specification does not provide a reasonably representative disclosure of useful compounds which are soluble in any solvents.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 recites a range that is broader on the lower limit end of the range than the range recited in the claim that it is dependent from, claim 1. Claim 8 recites “from about 1 µm to about 20 µm” and claim 1 recites “from 1 µm to 30 µm”. Since the instant specification does not have a special definition for the term “about”, one of ordinary skill in the art would understand that “about 1 µm” equals +/- 10% of 1 µm and therefore the lower limit of the range of instant claim 8 is outside of the range of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
New Claim Rejections - 35 USC § 112(b)
Applicant’s claim amendments have necessitated the following new grounds of rejection.
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.
Claims 1-4 and 8-26 are rejected under 35 U.S.C. 112(b), 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 1-4 and 8-26 in that claim 1 recites the limitation "the therapeutic agent" in line 14. There is insufficient antecedent basis for this limitation in the claim. Claim 1 previously recites “at least one therapeutic agent” in line 3 (emphasis added). Thus, it is unclear whether just one, more than one, or all of the therapeutic agents are being referenced in line 14 and must be taste-masked. Amending claim 1 to recite “the at least one therapeutic agent(s)…”, would overcome this rejection.
Claim 3 is unclear in that it recites “a solvent-soluble material…solvent-soluble polymers…” in lines 8-9. Based on the claim and the originally filed specification (i.e., no special definition of solvent), it is unclear what solvent the material needs to be soluble in in order to read on the limitation. Is it a polar or non-polar solvent? Is it a particular solvent? Or can it be any solvent? Thus, the metes and bounds of the claims cannot be determined and the claims are indefinite.
Claims 9-10 and 17-26 also recite “the therapeutic agent” and are all dependent on claim 1, which recites “at least one therapeutic agent” in line 3 (emphasis added). Thus, it is unclear whether just one, more than one, or all of the therapeutic agents are being referenced.
Claim 16, which is dependent on claim 1, is unclear as it recites “…wherein the pharmaceutical composition comprises from about 1% to about 100% by weight of the drug-resin particles”. Claim 1 requires that the composition comprising micronized ion-exchange resin particles, at least one therapeutic agent and at least one dispersing aid; however, if the drug-resin particles formed between the micronized ion-exchange resin particles and the at least one therapeutic agent was present in the composition at the highest level of 100%, then there would be 0% dispersing aid, which is required by independent claim 1. Thus, the metes and bounds of the claims cannot be determined and the claims are indefinite.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-4, 8-17, 20-21 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Lafon (FR 2676364; published: 11/10/92), as evidenced by Mastropietro et al. (Comprehensive Biomaterials II, 4.23.2.2.9: Ion-exchange resins, 2017).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
With regards to instant claim 1, Lafon is directed to a pharmaceutical composition comprising an aminobutanone derivative bound to an ion exchange resin having a particle size smaller than 200 micrometers [Abstract].
With regards to the resin particle limitations of instant claims 1, 8, 11-12 and 15, Lafon teaches that the resins are insoluble in saliva (which is useful for masking the taste) and soluble in gastric environment. The release of the compounds of formula I takes place in a gastric medium. Lafon teaches that the resin can be an anionic acrylic resin such as copolymers of methacrylic acid and methyl methacrylate such as those sold under the brands Eudragit L and S or U acrylic resins such as copolymers of dimethylaminoethyl methacrylate and neutral methacrylic acid esters such as those sold under the brand Eudragit E [p. 3]. Lafon also teach strongly acidic cationic exchange resins such as copolymers of styrene and divinylbenzene having sulphonic cations [p. 3].
With regards to the therapeutic agent limitations of instant claims 1, 17, 20-21 and 25, Lafon teaches wherein the therapeutic agent is buflomedil (and its HCl salt – i.e., acidic)
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, which treats peripheral vascular disease [p. 2]; buflomedil is basic, contains an amine group and is a vasodilator.
With regards to the dispersing aid limitation of instant claims 1 and 3, Lafon teaches compositions comprising mannitol (i.e., the claimed dispersing agent) [Ex. 8].
With regards to instant claim 2, Lafon teaches that the composition components (buflomedil hydrochloride – 320 mg containing 150 mg of cationic resin, sweetener, flavoring agent, dextran, aerosol 200, mannitol (i.e., dispersing aid) and water as intermediate solvent) are mixed to form a fluid suspension and freeze dried and heat sealed [Ex. 8].
With regards to instant claims 1 and 4, Lafon teaches that the composition can be presented in conventional dosage forms such as powders in sachets, capsules, tablets, granules (i.e., solid dosage forms) [p. 3].
With regards to instant claims 9-10, Lafon teaches 8.95 g of buflomedil base and 3 g of resin (Amberlite IRP-64) (i.e., approximately 3:1). As indicated in MPEP §2144.05(I): “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” “A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985).”
With regards to instant claim 14, Lafon exemplifies Amberlite IRP-64 as a resin in its examples. As evidenced by Mastropietro et al., Amberlite IRP-64 is a crosslinked-methacrylic acid and divinylbenzene copolymers [4.23.2.2.9 Ion-exchange resins].
With regards to instant claim 16, Lafon teaches wherein the compositions comprise between 1% and 100% by weight of the drug-resin particles [see Examples].
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Lafon does not specifically teach wherein the resin has a size of from 1 to 30 micrometers or from about 1 micrometer to about 20 micrometers, as required by instant claims 1 and 8.
However, Lafon teaches that the commercial resins which are used in the invention generally have a large particle size and a reduction in the particle size must be carried out. For this purpose, one can perform grinding either in the wet phase (microbead mill) or in the dry phase (ball mill for example) allowing the particle size to be reduced to a value of 30 to 100 micrometers or air jet micronization to obtain a particle size of 5 to 50 micrometers and optionally a double micronization to obtain a particle size of 5 to 30 micrometers (overlaps with the ranges recited in instant claims 1 and 8) [p. 3]. It is also noted that Lafon claims wherein the resin has a size of 5-50 micrometers [claim 4].
Lafon does not specifically teach wherein in less than 60 seconds the solid dosage form provides uniform dispersion of the resin-therapeutic agent complexes with less than 1 wt% of the micronized resin particles in the form of aggregates when re-dispersed/constituted in a liquid medium and a reduced gritty mouth feel compared to a dosage form containing resin particles with particle sizes larger than 30 µm, as required by instant claim 1. Lafon does not specifically teach wherein the resin particle has an ion-exchange capacity of less than 6 milliequivalents per gram of dry resin, as required by instant claim 13.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
However, as the range taught by the prior art is overlapping with the claimed range, MPEP §2144.05(I) provides support for a prima facie case of obviousness: “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.”
Lafon do not disclose the properties as recited in claims 1 and 13. However, the invention as claimed is not structurally distinguishable from the disclosure of Lafon and therefore, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are inherent in the composition taught by the prior art. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed composition with that of the prior art, the burden of proof is shifted to the Applicants to show an unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art; i.e., to prove that the properties are not inherent. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.). As recited in MPEP §2112.01 (II): “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Claims 18-19 and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Lafon (FR 2676364; published: 11/10/92), as evidenced by Mastropietro et al. (Comprehensive Biomaterials II, 4.23.2.2.9: Ion-exchange resins, 2017) as applied to claims 1-4, 8-17, 20-21 and 25 above, and further in view of Mehta et al. (US 2010/0166858; published: 07/01/10).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Lafon, as evidenced by Mastropietro, teach the limitations of instant claims 1-4, 8-17, 20-21 and 25 (see above rejection).
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Lafon does not specifically teach the species and types of active agents listed in instant claims 18-19 and 22-24.
However, such active agents were known and routinely used in the prior art as drugs complexed with ion-exchange resins as taught by Mehta. Mehta is directed to modified release formulations containing drug-ion exchange resin complexes [Title]. Mehta teach a similar product wherein the drug in the ion exchange resin matrix is selected form the group consisting of morphine, oxycodone, albuterol, methylphenidate, dextromethorphan, codeine, tramadol, pseudoephedrine, phenylephrine, hydrocodone, venlafaxine, ibuprofen, oxybutynin, clonidine, dexchlorpheniramine, fexofenadine, diphenhydramine, phenylpropranolamine, chlorpheniramine, amphetamine, naproxene, diclofenac, paroxetine, amoxicillin and pharmaceutically acceptable salts thereof (italicized species are listed in instant claims 18-19, bolded species are listed in instant claim 22, underline species are listed in instant claims 23-24) [see entire reference; e.g., claim 24].
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the composition of Lafon by replacing the active agent buflomedil with those taught by Mehta to achieve the predictable result of obtaining a drug formulation used to treat other diseases/disorders/symptoms.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Lafon (FR 2676364; published: 11/10/92), as evidenced by Mastropietro et al. (Comprehensive Biomaterials II, 4.23.2.2.9: Ion-exchange resins, 2017) as applied to claims 1-4, 8-17, 20-21 and 25 above, and further in view of Vachon (US 2017/0304815; published: 10/26/17).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Lafon, as evidenced by Mastropietro, teach the limitations of instant claims 1-4, 8-17, 20-21 and 25 (see above rejection).
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Lafon does not specifically teach wherein the therapeutic agent is, for example, an anti-bacterial agent, as required by instant claim 26.
However, such active agents were known and routinely used in the prior art as drugs complexed with ion-exchange resins as taught by Vachon. Vachon is directed to biologically activated ion-exchange polymer salts [Abstract]. Vachon teaches combining ion-exchange resins such as those taught by Lafon (Amberlite IRP 64) and doxycycline (dox), an anti-bacterial agent [see Table 2A-2B].
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the composition of Lafon by replacing the active agent buflomedil with doxycycline taught by Vachon to achieve the predictable result of obtaining a drug formulation used to treat other diseases/disorders/symptoms.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Maintained and Modified Double Patenting
Applicant' s claim amendments have necessitated the following modified grounds of rejection (based on new claim numbering/cancellations).
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-4, 8-23 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 10-19, 21 and 24-37 of copending Application No. 17/618,033 (US 20220257469) in view of US 11602507 to Guditi, WO 91/13612 to Grattan, Singh et al (FABAD J. Pharm. Sci., 32, 91-100), US 6193962 to Metcalf et al., and US 5296228 to Chang.
Copending claims 1-37 are directed to a unit dose system comprising a self- dispersible dry pharmaceutical composition that comprises at least one active agent, a taste-masking agent, a matrix forming agent and further include an ion exchange resin that is micronized to a size of less than 50 microns (copending claim 13). Claim 14 of the copending claims recite the instant claimed resins (see instant claim 15).
The copending claims recite self-dispersible composition, copending claims recite employing a taste masking agent and a matrix forming agent. The above copending claims lack the instant particle size of 1-30 microns, dispersion agent, and the amounts or ratio of active to ion exchange resins.
In this regard, Guditi teaches an oral extended release composition, comprising memantine or its pharmaceutically acceptable salt as an active ingredient, anionic and cationic exchange resins (col. 11, I 38-41) and in particular, cholestyramine (Duolite), AMBERLITE IRP-169 etc; release retardant, extended release coating system and the composition further comprising diluents, viscosity increasing agents, glidants, sweeteners, stabilizing agents, preservatives and other pharmaceutically acceptable excipients, wherein the drug-resin complex and drug-resin complex matrix particulates
and coated drug-resin complex particulates have the specific particle size range (abstract). For the ratios of active to resin in claims 9-10 (5:1 to 1:100 or 2:1 to 1:20 respectively), Guditi teaches 1:0.5 to 1:3.5 and most preferably 1:1 to 1:3 (col. 12, I 4- 10). For the claimed dispersing agent of claim 2, Guditi teaches stabilizing agents (col. 6-7) and further specifically mentions mixing polyvinylpyrrolidone (col. 9, I 18-26) of instant claim 3. For Instant claim 4, Guditi teaches an oral suspension, see col. 17, 10- 43).
Thus, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to modify the claims of the copending claims and include the stabilizing agents (also read on matrix forming agents) so as to provide a dispersion as well as stabilization of the copending composition because Guditi suggests including PVP for preparing the drug-resin complexes, which meet the instant matrix forming agent. While Guditi does not teach PVP as dispersing agent, a compound and its property are inseparable. Accordingly, one of an ordinary skill in the art would have expected the composition of copending claims modified by including PVP of Guditi, would result in the instant dispersible composition.
While copending claims do not teach the exact claimed amounts, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to optimize the amounts of resin and active agents in preparing the pharmaceutical composition because Guditi suggests 5% to 15% of the active agent and 5 to 25% resin complexation ingredient (see the described embodiments in col. 6-7) for providing extended release of the active agents, and the amounts taught by Guditi overlap with the ranges of concentrations of instant claims 5 and 16.
Guditi does not explicitly teach the claimed limitations- less than 1 wt% resin microparticles in the form of aggregates, taste masking and reduced gritty feeling.
Singh teaches ion exchange resins in drug delivery and therapeutic applications and include both resins such as cross-linked divinyl benzene and styrene polymers (p 92, col. 2). Singh teaches that excessive bitterness of the active principal ingredients (API) in oral formulations is the major taste problem faced by the pharmaceutical industry and that among the numerous available taste-making methods, ion resin exchange resins are inexpensive, simple, rapid and a cost-effective method of taste masking. Table 1 of Singh teaches taste masking of different types of bitter drugs. Singh further teaches that the drugs adsorbed on to ion exchange resin have reduced agglomeration and reduced hygroscopicity and provide a uniform and excellent flowability to the formulation (p 95).
Thus, it would have been obvious, from the teachings of Singh et al, for one of an ordinary skill in the art before the effective filing date of the instant invention that the ion exchange resins of copending claims (modified by Guditi) provide the claimed properties i.e., effective taste masking of bitter drugs that are absorbed on the ion- exchange resins (of Guditi), provide uniformity of dispersion with very little aggregation. One of an ordinary skill in the art would have expected the claimed properties because Singh also teaches the different (cationic and anionic exchange resins) and drugs that are within the scope of the instant claimed invention.
Instant claims have been amended and now requires "micronized ion-exchange resin particles having particle sizes from 1 micron to 30 micron". It is noted that the
previous particle sizes claims refer to the drug-resin complex and not ion-exchange resin particles alone.
In this regard, the teachings of Guditi, Metcalfe, Grattan and Chang references, discussed above, have been incorporated herewith. Hence, it would have been obvious for one of an ordinary skill in the art to prepare drug-resinate complexes of copending claims, by employing smaller particle size of the ion exchange resin particles as well as the resin-drug complex i.e., smaller than 50 microns, 1-30 microns, for instance as small as18 microns, because Grattan teaches that drug-resin complexes with a particle size greater than about 50 micron are known to impart a gritty texture rendering the product unpalatable for oral consumption, even in liquid suspension (p 5, I 25-35), Metcalf teaches ion-exchange resin with a particle that falls within the claimed size and for providing a complex that not only imparts pleasant taste, mouth feel and also good bioavailability. Grattan teaches that small particle of resin offer a more complete release of drug from the resin and increased bioavailability (p 6, I 5-9) and Chang teaches that the particle sizes in the range of 1-50 microns enable easily passing through lacrimal glands and readily disperse in fluids (col. 7, I 4-12). Hence, one of an of ordinary skill in the art would have been motivated to reduce the size of ion-exchange resin particles as also the major amount of drug-ion exchange resin (25-75% or 50-100%) particles to lower than 50 or less than 20 microns with an expectation to provide taste masking as well as improved the bioavailability of the active in the complex. Grattan further teaches that a particle size greater than 50 microns is not preferable because the greater size impart a gritty texture rendering the product. 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).
This is a provisional nonstatutory double patenting rejection.
Claims 1-4 and 8-26 are provisionally rejected on the ground of 8nonstatutory double patenting as being unpatentable over claims 1-7, 10-19, 21 and 24-37 of copending Application No. 17/618,033 (US 20220257469) in view of US 11602507 to Guditi, and US 6193962 to Metcalf et al., WO 91/13612 to Grattan, US 5296228 to Chang and Singh et al (FABAD J. Pharm. Sci., 32, 91-100), as applied to claims 1- 5, 7-18, 20-22 and 25, and further in view of US 20130034503 to Howard et al (Howard).
The copending claims mentioned above fails to teach the specific therapeutic agents of claim 24.
Guditi, Metcalf, Grattan, Chang and Singh fail to teach the claimed Howard teaches incorporating a variety of active agents in the composition and include instant claimed compounds [0102-0103] such as ibuprofen, naproxen etc (claims 17-19), morphine (of instant claims 23-24) and antimicrobial agents (instant claims 23-26). The composition can be in the form of a tablet, capsule or a suspension [0098 &0136]. Additionally, Howard exemplifies ion exchange resin composition comprising hydrocodone and pseudoephedrine (claims 20-22). The exemplified compositions of Howard include hydroxypropyl methyl cellulose, which read on the instant dispersion (claims 2 and 3). Example 1 of Howard teaches a drug to resin ratio of 12:1.
Therefore, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to prepare ion exchange resin -drug complexes of copending claims (modified by Guditi, Metcalf, Grattan, Chang and Singh) with any type of drugs including those taught by Howard i.e., ibuprofen, naproxen or morphine, and thus arrive at the instant claims. One of an ordinary skill in the art would have been motivated to do so because Howard teaches the use of ion exchange resin technology to eliminate or to diminish the overdose hazard and adverse events if excessive quantities of the inventive product are accidently or intentionally ingested, and Singh teaches the use of ion exchange resin technology to be cost-effective and for providing effective release of the drug.
Response to Arguments
Applicants’ request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an objection or requirements as to form (see MPEP 37 CFR 1.111(b) and 714.02). Accordingly, the rejection will be maintained until a terminal disclaimer is filed or claims are amended to obviate the rejection.
Conclusion
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/GENEVIEVE S ALLEY/Primary Examiner, Art Unit 1617
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