DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/18/2026 and 04/18/2026 has been entered.
Status of the Claims
Claims 1-33, 35, 37, 39, 41, 43, 47, and 49 had been cancelled in a previous correspondence. Claims 34, 36, 38, 40, 42, 44-46, 48, and 50-57 are pending. Claims 50-57 are withdrawn without traverse.
Claims 34, 36, 38, 40, 42, 44-46, and 48 are under current examination.
All rejections not reiterated have been withdrawn.
Claim Objections
Applicant is advised that should claim 45 be found allowable, claim 48 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 42, 44-46 and 48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
This is a new matter rejection. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Specifically, the examiner is unable to locate support in the instant application or the applications to which the instant application claims priority for the negative limitation in claim 42, line 9 requiring “wherein said drug cores are formed without extrusion-spheronization”.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the new matter concerns outlined above.
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 34, 36, 38, 40, 42, 44-46 and 48 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 34, line 22 recites “not less than 65% of the ranolazine in 4 hours of measurement in said apparatus”. This phrase renders the claim indefinite because it does not contain a verb stating what becomes of the not less than 65% of the ranolazine” (e.g. “is released” as in the preceding conditional phrases), therefore the conditions required of the claimed invention are unclear.
Claim 36 is indefinite because the claim does not recite a conjunction at the end of list of shapes the cores may take, therefore it is unclear whether all shapes are required or only one.
Claim 38 is indefinite because the claim recites the conjunction “and” at the end of list of substances; however, the claim also indicates that mixtures of the substances are suitable, implying that any one substance may be present in the claimed invention, therefore it is unclear whether all substances are required for methods falling within the metes and bounds of the instant claims or only one of the listed substances.
Claim 40 is indefinite because it recites improper Markush language. A Markush group is a closed list of alternatives; however the phrase “comprising of” implies that other substances that are not expressly listed may be present as the claimed polymer.
Please refer to MPEP 2173.05(h): When materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in the conventional manner, or alternatively. For example, if “wherein R is a material selected from the group consisting of A, B, C and D” is a proper limitation, then “wherein R is A, B, C or D” shall also be considered proper.
Claim 42 recites the limitation "the particulate composition" in line 15. There is insufficient antecedent basis for this limitation in the claim.
Claim 42 recites the limitation "the ranolazine" in each of lines 24, 26, and 28. There is insufficient antecedent basis for this limitation in the claim.
Claim 44 is indefinite because the claim does not recite a conjunction at the end of list of shapes the cores may take, therefore it is unclear whether all shapes are required or only one.
Claim 45 is indefinite because it recites improper Markush language. A Markush group is a closed list of alternatives; however the phrase “comprising of” implies that other substances that are not expressly listed may be present as the claimed polymer.
Please refer to MPEP 2173.05(h): When materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in the conventional manner, or alternatively. For example, if “wherein R is a material selected from the group consisting of A, B, C and D” is a proper limitation, then “wherein R is A, B, C or D” shall also be considered proper.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined above.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 34, 36, 38, 40, 42, 44-46, and 48 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Dow et al. (US 5,506,229; issue date: 04/09/1996; of record) in view of Gant et al. (US2008/0312247; publication date: 12/18/2008; of record) and Venkatesh (US 2006/0246134; publication date: 11/02/2006; of record).
With respect to claims 34 and 42, Dow discloses a controlled release formulation of ranolazine base (col 11-12). The formulation is formed by dry mixing (i.e. blending a powder; therefore the examiner considers both the ranolazine and the polymer both to be powders) 90 parts by weight ranolazine with 10 parts by weight (i.e. a 9:1 weight ratio) microcrystalline cellulose (i.e. a drug binding polymer) followed by extrusion spheronization to form microspheres (i.e. a plurality of drug cores) of size ranging from 0.5 to 1.4 mm, which are then coated with an appropriate release rate-controlling polymer and put into a hard shell capsule. The weight ratio of ranolazine to drug binding polymer (microcrystalline cellulose) falls within the range recited in the instant claims and the particle size range disclosed by Dow overlaps with the particle size recited in the instant claims (see MPEP 2144.05). With regard to the limitation requiring the ranolazine/pharmaceutically active substance to be in reversible association with the drug-binding polymer, the examiner considers this feature to be inherent because both the drug and the polymer are identical to those used in the instant invention (see e.g. page 1 of the instant specification which indicates that microcrystalline cellulose is a “drug binding polymer” according the instant invention). Moreover, “reversible association” reads on weak intermolecular forces that exist between any combination of substances that are physically in contact with one another and therefore inherently are present between the ranolazine and microcrystalline cellulose in Dow’s cores. The formulation is a controlled release formulation and there are release coating polymers therefore the examiner considers the invention to embrace methods of extending duration between doses of ranolazine, as recited in instant claim 42. With regard to the limitation of instant claim 34 and 42 requiring the particulate composition to be in the form of a powder or granulation, the examiner considers the coated particles disclosed
Dow does not disclose the solubility or permeability or the identity of the release rate controlling polymers, nor the ranolazine release profile.
Gant discloses that ranolazine has a half-life of less than two hours and must be taken frequently (0090).
Venkatesh discloses a multiparticulate dosage form for delivering one or more basic active pharmaceutical ingredients (API) to achieve a target pharmacokinetic (PK) profile (abstract). The composition is suitable for once or twice daily dosing and contains one or more bead populations that can provide a sustained release profile (0008). These bead populations contain an active core that is coated with a release rate controlling polymer that includes a water-insoluble polymer to control release (0008 and 0017) and are therefore structurally very similar to the particulate composition disclosed by Dow. Claimed water-insoluble polymers for Venkatesh’s invention include ethylcellulose, which the instant specification indicates to be water permeable.
With regard to the extended release profiles required by instant claims 34 and 42, it would have been prima facie obvious to optimize the formulation disclosed by Dow with the understanding of how to extend PK profile in coated core particulate compositions provided by Venkatesh. The skilled artisan would have been motivated to extend release of ranolazine because this substance has a very short half-life and an extended release formulation could reduce the number of doses required to maintain an effective plasma concentration of the drug. This, in turn, is more convenient for patients and increases patient compliance. The skilled artisan would have had a reasonable expectation of success because Venkatesh discloses details as to how to optimize polymer coated core multiparticulates such as those disclosed for controlled release by Dow to achieve an extended release profile. With regard to the specific pharmacokinetic parameters recited in instant claims 34 and 42, it would have been merely a matter of routine testing for one of ordinary skill to optimize the parameters disclosed in the prior art to achieve the claimed drug release kinetics.
With regard to the limitation of instant claims 34 and 42 requiring the coating to completely surround the drug cores, in the example cited above, Dow states that the microspheres are “coated”, and throughout the document, Venkatesh describes coating multiparticulates to control release of drug. There is no mention of partially coating the particulates in either of the references that describe controlled release coatings (Dow or Venkatesh). The examiner considers both disclosures to describe “completely surrounding” the microspheres with the extended release coating, absent evidence to the contrary. Moreover, one having ordinary skill would have recognized that any coating would not influence release of drug from a region where it was not present, so the choice to completely or partially coat a multiparticulate dosage form would have provided the artisan of ordinary skill with an additional mechanism to modulate drug release profile. For these reasons, the examiner does not consider the limitation “applying an extended release coating completely surrounding each of the plurality of drug cores” to patentably define over the cited prior art.
Claim 42 requires the limitation that the drug cores are formed without extrusion-spheronization. Although Dow’s example describes forming the particles by extrusion-spheronization, Gant teaches “[s]uch multiparticulates may be made by the processes know to those skilled in the art, including wet- and dry-granulation, extrusion/spheronization, roller-compaction, melt-congealing” 0241; Venkatesh teaches that in addition to this method, “drug-containing microgranules or pellets may be prepared by rotogranulation, high-shear granulation and extrusion-spheronization or compression (as mini-/micro-tablets (about one/two mm in diameter)) of the drug, a polymeric binder and optionally fillers/diluents” (0019). It would have been prima facie obvious for one of ordinary skill to manufacture the microspheres disclosed by Dow by any other known method because this would merely have been applying a known technique to a known device (method, or product) to yield predictable result (see MPEP 2143(I)(D)). Notably, although Dow discloses one example in which the multiparticulates are formed by extrusion-spheronization, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2123(II).
With regard to claims 35 and 43, Venkatesh indicates that drug release profiles can be determined in a type 2 apparatus rotating at 50 rpm. This method is routinely used in the pharmaceutical arts to estimate drug release in the body. See MPEP 2144.07 regarding obviousness of art-recognized suitability.
With regard to claims 36 and 44, Dow discloses spheres which falls within the scope of “spheroidal”.
With regard to claims 40 and 45, as noted above, Venkatesh discloses ethylcellulose.
With regard to claims 38 and 46, Venkatesh discloses adding the plasticizers triacetin, tributyl citrate, triethyl citrate, acetyl tri-n-butyl citrate (0044). It would have been prima facie obvious to add these plasticizers the polymer coating. The skilled artisan would have been motivated to do so in order to reduce brittleness and thereby increase durability of the coating. The artisan of ordinary skill would have had reasonable expectation of success because Venkatesh indicates that these substances are suitable plasticizers for pharmaceutical coatings.
Claims 42, 44-46 and 48 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Venkatesh (US 2006/0246134; publication date: 11/02/2006; of record in view of Boghani et al. (US 2006/0263480; publication date: 11/23/2006).
With regard to claim 42, Venkatesh discloses a particulate composition (abstract: “[a] unit multiparticulate dosage form”) comprising one or more basic active pharmaceutical ingredients designed to achieve target pharmacokinetic (PK) profiles comprising coated particles (i.e. coated cores; abstract). Venkatesh discloses a group of parameters that can be adjusted to achieve target PK profiles suitable for once or twice daily dosing (abstract). Venkatesh describes the formulation as providing a single targeted sustained-release profile over several hours after oral administration, with or without an immediate release pulse (0037). The active containing core may be prepared by, inter alia, granulation into micro/minitablets (i.e. particles) with a binder and an optional dissolution rate controlling polymer, followed by coating the micro/minitablets (i.e. particles). Thus, the resulting particles are a granulation as required by instant claim 42. The binders disclosed are polymers (e.g. PVP, HPMC, hydroxypropylcellulose, carboxyalkyl celluloses, PEO, polysaccharides; 0040). The examiner considers the phrase “reversible association” to read on weak intermolecular forces that exist between any combination of substances that are physically in contact with one another and therefore inherently are present in embodiments of Venkatesh having a binder and optional release rate controlling polymer and a drug within matrix core. The examiner considers the limitation requiring “combining particles of a pharmaceutically active compound and particles of one or more drug binding polymers to form a homogeneous powder drug-polymer blend” to read on or be an obvious variation of the granulation process disclosed by Venkatesh because the drug and binder must be combined, and if solid must be in particle form in order to be mixed to homogeneity by the step “blended together in a high-shear granulator or a fluid bed granulator. The active core that is coated with a release rate controlling polymer that includes a water-insoluble polymer to control release (0008 and 0017). Claimed water-insoluble polymers for Venkatesh’s invention include ethylcellulose, which the instant specification indicates to be water permeable. Once the particulates are formed they may be filled into a capsule (Venkatesh: claim 18). With regard to the weight ratio of drug to drug-binding polymer (i.e. Venkatesh’s binder or release rate controlling polymer), the quantity would depend upon the identity of the drug and binder/release controlling polymer and desired dose and release profile. The examiner considers the relative proportions of the drug, binder, and release controlling polymer to be optimizable parameter that one having ordinary skill would have tested as a matter of course during design of a controlled release formulation of any given drug (see MPEP 2144.05).
With regard to the limitations of instant claim 42, lines 2-5 requiring that the combined particles of active compound and polymer be dry, Venkatesh discloses that the polymers may be used as a dry powder (0041), and that the granules can be produced by dry granulation (0043).
Claim 42 requires the limitation that the drug cores are formed without extrusion-spheronization. Venkatesh teaches that in addition to this method, “drug-containing microgranules or pellets may be prepared by rotogranulation, high-shear granulation and extrusion-spheronization or compression (as mini-/micro-tablets (about one/two mm in diameter)) of the drug, a polymeric binder and optionally fillers/diluents” (0019), therefore methods other than extrusion-spheronization were within the scope of the invention taught by Venkatesh, and therefore prima facie obvious.
Venkatesh discloses microtablets having diameter in the range of about 1 mm (0021) and therefore does not disclose the claimed range for particle diameter, although the examiner remarks that about 1 mm is close to the upper limit of the range recited in the instant claims.
Boghani, in the analogous art of delivery systems for edible compositions (abstract), discloses that particle size of a delivery system can be selected based on the desired rate of release (00099).
It would have been prima facie obvious to adjust particle size of the multiparticulate formulation as a variable that influences drug release profile because this was an art-recognized result-effective variable at the time of the instant invention (see MPEP 2144.05).
With regard to the specific pharmacokinetic parameters recited in instant claim 42, it would have been merely a matter of routine testing for one of ordinary skill to optimize the parameters disclosed in the prior art to achieve the claimed drug release kinetics dependent upon the identity of the drug and the desired PK profile.
With regard to claim 43, Venkatesh indicates that drug release profiles can be determined in a type 2 apparatus rotating at 50 rpm. This method is routinely used in the pharmaceutical arts to estimate drug release in the body. See MPEP 2144.07 regarding obviousness of art-recognized suitability.
With regard to claim 44, Venkatesh discloses pellets which falls within the scope of “spheroidal”.
With regard to claim 45, as noted above, Venkatesh discloses ethylcellulose.
With regard to claim 46, Venkatesh discloses adding the plasticizers triacetin, tributyl citrate, triethyl citrate, acetyl tri-n-butyl citrate (0044). It would have been prima facie obvious to add these plasticizers the polymer coating. The skilled artisan would have been motivated to do so in order to reduce brittleness and thereby increase durability of the coating. The artisan of ordinary skill would have had reasonable expectation of success because Venkatesh indicates that these substances are suitable plasticizers for pharmaceutical coatings.
Response to Arguments
Applicant's arguments filed 04/17/2026 have been fully considered but they are not persuasive.
In several locations Applicant argues that the examiner may have implicitly assumed the benefit of Applicant’s disclosure in appreciating how particular formulation features could be combined.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Throughout pages 11-14, Applicant argues that Dow provides limited guidance for a person of ordinary skill seeking to design and implement an extended release ranolazine formulation having the particularly claimed release profile. On pages 11-12, Applicant argues further that Dow and Gant each separately not disclose or suggest the entirety of the claimed invention.
In response to applicant's arguments against the references 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).
On page 11, Applicant argues that Dow provides limited guidance for a person of ordinary skill seeking to design and implement an extended-release ranolazine formulation having the particularly claimed release profile and Dow does not disclose or suggest the claimed combination of dry particle blending, formation of drug cores from a homogeneous drug-polymer powder blend, and application of a water-insoluble, water permeable coating to produce microparticles that meet the expressly recited particle size distribution and dissolution profile.
Regarding the active method steps, the only step not expressly taught by Dow is the modestly broader “release-controlling polymer” coating vis a vis the claimed “water-insoluble, water permeable polymer” coating. This limitation is not a patentable distinction because water-insoluble, water permeable polymer coatings were well known in the art as of the instant effective filing date, as detailed in the rejection supra. The slightly more specific release profile recited in the claims does not patentably define over the prior art because this would have been optimizable by the artisan of ordinary skill, directed by Dow to seek extended release of the drug.
On page 12, Applicant argues that Gant directs the skilled artisan away from solutions of the type claimed by Applicant and toward fundamentally different approaches for addressing ranolazine’s pharmacokinetic limitations. On page 13, Applicant argues further that Gant teaches away from the claimed invention: The disclosure is directed to chemical modification to alter biological behavior, citing teachings in Gant not relied upon in the rejection. Applicant argues that Gant’s focus on changes to the chemical entity to address pharmacokinetic challenges diverges from Dow’s disclosure of controlled release. Applicant asserts that “Gant implicitly signals to the skilled artisan that formulation-based solutions are unsuitable, reinforcing a direction away from multiparticulate formulation engineering. Applicant argues that the obviousness rejection requires the artisan of ordinary skill to disregard Gant’s central thesis. Applicant speculates that one of ordinary skill would have expected further formulation refinement would not be expected to succeed. On page 14, Applicant argues further that Gant teaches away from the claimed invention, pointing out that where a reference suggests that a particular approach is unlikely to succeed or focuses on alternative solutions to the same problem, such a reference teaches away from the claimed invention. Applicant argues that Gant’s focus on chemical modification and express statements regarding limitations of extended release formulations would lead one of ordinary skill away from the claimed invention.
The examiner respectfully disagrees that the artisan of ordinary skill would find any teaching away in Gant. "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). (See MPEP 2123(I)). Although Gant states that “extended release ranolazine formulations have to be taken twice daily” (0090), the examiner does not consider this to be the type of statement that would have discouraged one of ordinary skill from further investigating the benefits of extended release ranolazine formulations. Applicant overstates the extent to which this statement detracts from extended release formulations, and points out that the instantly claimed invention describes a release profile that would be suitable for twice daily dosing (see also page 53 of the instant specification). Nowhere does Gant indicate that extended release formulations for ranolazine would be inoperable. Finally, with regard to the argument that other solutions besides Applicant’s multiparticulate controlled release formulation were known in the art at the time of filing (e.g. design of a prodrug to lengthen half-life), the examiner points out that the existence of alternative solutions does not constitute a teaching away.
On page 14, Applicant asserts that Venkatesh does not disclose or suggest forming drug cores from a homogeneous dry drug-polymer blend with reversible association prior to coating or applying a coating that completely surrounds the cores to achieve the amended particle size distribution and dissolution profile.
The examiner respectfully disagrees with this statement for exactly the reasons set forth in the obviousness rejection above.
On pages 15-16, Applicant quotes sections of Venkatesh describing their pulsatile release formulation. On page 17, Applicant argues that viewed collectively, the references do not appear to suggest that controlled, non-pulsatile absorption kinetics could be engineered through multiparticulate architecture in the manner claimed.
Venkatesh describes the formulation as providing a single targeted sustained-release profile over several hours after oral administration, with or without an immediate release pulse (0037). Finally, Applicant appears to distinguish between the pulsatile release formulation of Venkatesh and the instant release profile; however, the instant release profile does not exclude a pulsatile release pattern, it merely dictates the total quantity of drug released after given time points under the recited test conditions. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., exclusion of a pulsatile release formulation) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Finally, the examiner does not consider Venkatesh to teach away from the instant invention because Venkatesh provides choices for components of their formulation that would allow one of ordinary skill to tailor the release profile as desired, as stated by Venkatesh in the abstract.
On page 16, Applicant argues that Venkatesh describes a formulation that has a lag-time.
The examiner points out that this is with regard to a subset of the beads. The entire formulation may also contain beads having an immediate release profile or an immediate release coating. The disclosure is not limited to formulations having a lag time. The discussion on page 16-17 of the lag time described by Venkatesh incompletely represents the disclosure and is not material to the reasoning underlying the obviousness rejection.
On page 17, Applicant argues that the combination of Dow, Gant, and Venkatesh yields a broad array of potential release strategies covering a wide spectrum of behaviors.
This is not found persuasive. In response, simply because the prior art "discloses a multitude of effective combinations does not render any particular formulation less obvious." Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). "[P]icking and choosing may be entirely proper in the making of a 103, obviousness rejection." In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Furthermore, it is noted that Applicants do not identify secondary consideration demonstrating criticality or anything unexpected about the combination of claimed steps in the instant application.
On page 19, Applicant argues that Boghani fails to teach or suggest the amended pharmaceutical manufacturing process or dissolution behavior.
This is not persuasive because Boghani was not relied upon for such. In response to applicant's arguments against the references 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).
On pages 19-20, Applicant argues that Boghani is directed to delivery systems for edible compositions such as chewing gum and confectionary products, with release measured over minutes and not systemic pharmacokinetics. Applicant argues that Boghani is not reasonably directed to the technical problem addressed by Applicant.
The examiner respectfully disagrees that Boghani is non-analogous art within the meaning of 35 USC 103. Boghani is directed to releasing an chemical compound into the body, and is therefore reasonably pertinent to the problem solved by Applicant. Moreover, in this case, Boghani solves the same problem, again, release of a chemical compound that has been formulated into particles into the body.
On page 20, Applicant argues that the prior art teachings describe an unpredictable system.
The examiner respectfully disagrees. The teachings of the combined references would convey to one of ordinary skill a routine method of optimizing drug release from a multiparticulate formulation. Indeed as mentioned previously, Venkatesh states that their formulation may be optimized to achieve any target PK profile (abstract).
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 42, 44-46, and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,463,611 (of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claims.
Inter alia, the claims of the ‘611 patent embrace a particulate composition, wherein the particulate composition comprises:
(a) a biologically active core, said biologically active core comprising (i) naproxen, a pharmaceutically acceptable salt of said naproxen, or a combination thereof and (ii) a drug binding polymer comprising a silicified high density microcrystalline B cellulose composed of 98% microcrystalline cellulose and 2% colloidal silicon dioxide, wherein said naproxen, said pharmaceutically acceptable salt of said naproxen, or said combination thereof is in reversible association with said drug binding polymer and in a weight ratio therewith of from about 20:1 to about 1:2; and
(b) a coat, said coat comprising a membrane-forming polymer, said membrane-forming polymer comprising ethylcellulose and surrounding said biologically active core, wherein the particulate composition comprises microparticles/microparticulates having average diameter of from about 100 μm to about 900 μm.
The coating polymers may be water insoluble and water permeable.
The release profile required by the ‘611 patent narrowly embraces the drug release profile recited in the instant claims.
The examiner considers the invention of the ‘611 patent to be a multiparticulate dosage form for extended release drug delivery.
The claims of the ‘611 patent do not recite method steps for forming the multiparticulate composition; however, in order for the drug and polymer to be present in the core and in reversible association, they must first be mixed and one would be motivated to make a homogeneous mixture of drug and polymer to assure equal quantities of drug throughout the formulation. In order for an extended release coating to be present the cores must be coated.
Thus, the ‘611 claims render obvious the steps of making the clamed particulate dosage form by mixing the claimed drug and polymer such that they are homogeneous and form reversible association, forming the cores, and coating the cores with the claimed coating.
The claims of the ‘611 patent are silent with regard to the step of mixing the particles in a dry state, and do not expressly state that the cores are formed without extrusion-spheronization.
Venkatesh discloses a multiparticulate dosage form for delivering one or more basic active pharmaceutical ingredients (API) to achieve a target pharmacokinetic (PK) profile (abstract). The composition is suitable for once or twice daily dosing and contains one or more bead populations that can provide a sustained release profile (0008). These bead populations contain an active core that is coated with a release rate controlling polymer that includes a water-insoluble polymer to control release (0008 and 0017). Thus, Venkatesh discloses similar formulations to those of the ‘611 patent. The cores can be formed by inter alia dry granulation (0043) and there are many alternatives known to the artisan of ordinary skill for forming cores other than extrusion-spheronization: drug-containing microgranules or pellets may be prepared by rotogranulation, high-shear granulation and extrusion-spheronization or compression (0019). It would have been prima facie obvious for one of ordinary skill to manufacture the multiparticulate cores claimed in the ‘611 patent by any other known method because this would merely have been applying a known technique to a known device (method, or product) to yield predictable result (see MPEP 2143(I)(D)).
With regard to claim 43, Venkatesh indicates that drug release profiles can be determined in a type 2 apparatus rotating at 50 rpm. This method is routinely used in the pharmaceutical arts to estimate drug release in the body. See MPEP 2144.07 regarding obviousness of art-recognized suitability.
With regard to claim 44, Venkatesh discloses that the multiparticulates can come in many shapes such as spherical beads (0008).
With regard to claim 46, Venkatesh discloses adding the plasticizers triacetin, tributyl citrate, triethyl citrate, acetyl tri-n-butyl citrate (0044). It would have been prima facie obvious to add these plasticizers the polymer coating. The skilled artisan would have been motivated to do so in order to reduce brittleness and thereby increase durability of the coating. The artisan of ordinary skill would have had reasonable expectation of success because Venkatesh indicates that these substances are suitable plasticizers for pharmaceutical coatings.
Claims 34, 36, 38, are 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,463,611 (of record) Venkatesh (US 2006/0246134; publication date: 11/02/2006) as applied to claims 42, 44-46, and 48 above and further in view of Gant et al. (US2008/0312247; publication date: 12/18/2008).
Inter alia, the claims of the ‘611 patent embrace a particulate composition, wherein the particulate composition comprises:
(a) a biologically active core, said biologically active core comprising (i) naproxen, a pharmaceutically acceptable salt of said naproxen, or a combination thereof and (ii) a drug binding polymer comprising a silicified high density microcrystalline B cellulose composed of 98% microcrystalline cellulose and 2% colloidal silicon dioxide, wherein said naproxen, said pharmaceutically acceptable salt of said naproxen, or said combination thereof is in reversible association with said drug binding polymer and in a weight ratio therewith of from about 20:1 to about 1:2; and
(b) a coat, said coat comprising a membrane-forming polymer, said membrane-forming polymer comprising ethylcellulose and surrounding said biologically active core, wherein the particulate composition comprises microparticles/microparticulates having average diameter of from about 100 μm to about 900 μm.
The examiner considers the invention of the ‘611 patent to be a multiparticulate dosage form for extended release drug delivery.
Gant discloses that ranolazine has a half-life of less than two hours and must be taken frequently (0090).
It would have been prima facie obvious to formulate the invention of the ‘611 patent to deliver ranolazine rather than naproxen. The artisan of ordinary skill would have been motivated to do so in order to extend the release of this agent in view of its short half-life, thereby reducing the number of doses that must be administered to achieve prolonged therapeutic plasma levels. The skilled artisan would have had reasonable expectation of success because Venkatesh indicates that the structure of multiparticulate formulations having polymer coated polymer/drug cores was known for providing extended release of drugs at the time of the instant invention.
With regard to the specific pharmacokinetic parameters recited in the instant claims, it would have been merely a matter of routine testing for one of ordinary skill to optimize the parameters disclosed in the prior art to achieve the claimed drug release kinetics.
Response to Arguments
Applicant's arguments filed 04/17/2026 have been fully considered but they are not persuasive. Applicant’s comment on page 20-21 that they will consider filing a terminal disclaimer upon an indication that the claims are otherwise in condition for allowance is noted.
Conclusion
No claims are allowed.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617
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