DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Priority
This application is a continuation of Applications 17/304,562 filed 23 June 2021 (abandoned), 17/095,985 filed 12 November 2020 (abandoned), 16/395,857 filed 26 April 2019 (abandoned), 15/163,445 filed 24 May 2016 (abandoned), 14/822,385 filed 13 October 2015 (abandoned), and 11/464,754 filed 15 August 2006 (now US 9,198,871). This application claims priority from US provisional applications 60/708,526 and 60/708,692, both filed 15 August 2005.
Examiner’s Note
Applicant's amendments and arguments filed 13 August 2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 13 August 2025, it is noted that claims 53 and 62 have been amended and no new matter or claims have been added.
Status of the Claims
Claims 53, 55, 58-63, and 66-69 are pending.
Claims 53, 55, 58-63, and 66-69 are rejected.
Claim Rejections - 35 USC § 103
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 of this title, 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 negatived 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 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 53, 55, 58-63, and 66-69 are rejected under 35 U.S.C. 103(a) as being unpatentable over Boedecker et al. (US 5,378,462) in view of Khanshab et al. (US 5,830,266) in view of Okumura et a. (US 6,426,091) in view of Mony et al. (US 3,950,508) as evidenced by Porter (Remington: The Science and Practice of Pharmacy, 21st Edition, published 2005) as evidenced by Gastric Juice (http://www.thefreedictionary.com/gastric+juice).
Boedecker et al. teaches a process for producing pancreatin micropellet cores which can be coated with a gastric juice-resistant film and having a pancreatin content of 65-85% comprising the steps of:
a) mixing 100 parts by weight of pancreatin with from 15 to 50 parts by weight of polyethylene glycol 4000 and a sufficient amount of a lower alcohol to achieve an extrudable consistency, to form an extrudable mixture,
b) pressing said extrudable mixture in an extruding press containing a piercing die having a hole diameter of 0.8-1.2 mm to form extrudates which break by themselves into extrudate fragments of a length suitable for transfer to a rounding apparatus, and
c) transferring the extrudate fragments to a rounding apparatus and breaking up the transferred fragments in said rounding apparatus with the addition of from 1.5 to 5 parts by weight of liquid paraffin and from 1.5 to 10 parts by weight of propan-2-ol, per 100 parts by weight of pancreatin, under conditions which round fracture edges, to form micropellet cores having a spherical to ellipsoidal shape and a particle size distribution in which at least 80% of the particles have a minor axis to major axis ratio in the range from 1:1 to 1:2, and
d) drying the micropellet cores obtained in step c) at a temperature in the range from 30° to 50°C (col 1, lns 65-68; col 2, lns 1-25). During this step, drying is carried out until the solvent content in the pellets is less than or equal to 1% (col 4, lns 32-34).
In the example given by Boedecker, the process is carried out to prepare micropellets with a diameter of from 0.7-1.4 mm, with pancreatin as the active agent, in which the cores are coated in a known manner with a solution comprising hydroxypropylmethylcellulose phthalate (HP55), dibutyl phthalate (plasticizer), paraffin, and silicone oil (dimethicone) (col 5, ln 45-col 6, ln 7), which is disclosed by the Applicant as a suitable film-forming agent used in the claimed process (specification pg 4, ln 10). It should be noted that Boedecker teaches a coating that is resistant to gastric juices or, in other words, stomach acid (see “Gastric Juice” reference). By definition, enteric coatings, as described in Porter, are such that they remain intact in the stomach and subsequently dissolve in the small intestine (pg 932, "Enteric Coatings”). Furthermore, Porter teaches that enteric coatings are useful for delaying the release of drugs that are inactivated by stomach contents, such as pancreatin (pg 932, “Enteric Coatings”). Hydroxypropyl methylcellulose phthalate is taught by Porter as being a useful polymer for enteric coatings (pg 933, ¶4). Therefore, the coating of Boedecker, described only as one that is resistant to gastric-juices, is being interpreted by the Examiner as being an enteric coating. Boedecker further teaches that known pharmaceutically customary adjuvants (excipients) may be added to the extrudable mixture (col 3, lns 34-37). The coating can further comprise conventional plasticizers (col 5, lns 30-35).
Regarding claims 60-61, Boedecker teaches that the pancreatin micropellets may be placed in oral dosage forms, such as capsules (col 5, lns 36-41). It is further taught that pancreatin is useful for treating digestive disorders including pancreatic (exocrine) insufficiency (col 1, lns 13-17).
Boedecker also does not teach the specific blend of plasticizers (triethyl citrate and cetyl alcohol or just cetyl alcohol).
Khanshab teaches coatings (col 1, lns 5-8) and further teaches that phthalate plasticizers such as dibutyl phthalate present health and toxicity problems (col 1, lns 39-42).
Okumura teaches a sustained release tablet of active agent theophylline. In the method, core particles of theophylline are coated with a mixture comprising a solvent such as a lower alcohol, a hydrophobic material, and a plastic excipient (col 2, Ins 64- 67; col 3, Ins 1-23). The plastic excipient is taught as being preferably selected from triethyl citrate or cetanol (aka cetyl alcohol), as required in the enteric coating of the instant invention (col 3, Ins 29-32). In a particular example, Okumura teaches a coating composition comprising ethylcellulose (a film-forming agent), cetanol (1.8%), and triethyl citrate (6.0%) (col 4, Ins 62-67; col 5, Ins 1-10). In a broader teaching, the plastic excipient can be included in from 10-50 parts by weight in relation to the enteric polymer (i.e. hydroxypropyl methylcellulose), which can be included in 5-150 parts by weight (col 3, lns 1-22). Furthermore, the composition is completely free of monomeric phthalic esters. Based on the broader teachings, the total amount of plastic excipient can be included in about 7% or higher based on the total weight of enteric polymer material (10 parts plasticizer in relation to 150 parts polymer is 7%). While theophylline is not the same as pancreatin, of the instant claims, Okumura teaches that their coating composition and process produces a tablet having superior sustained release effects (col 2, Ins 5-7).
Mony teaches a process of obtaining delayed action oral medications (col 1, Ins 4-6). In regards to the active agent, Mony teaches that among the suitable actives are theophylline and pancreatin (col 3, Ins 50-61).
The combined teachings of the prior art cited herein establish a prima facie case of obviousness over the instant claims. Regarding instant claim 53, Boedecker teaches preparing the pancreatin micropellet cores and then discloses the application of a gastric-juice resistant coating comprising a film-forming agent, a plasticizer, dimethicone, and an organic solvent. The amount of dimethicone (anti-sticking agent) is not specified, thus in lieu of evidence of an unexpected result, any amount would be obvious including 3% by weight.
Boedecker teaches, and Porter reinforces, that the gastric-juice resistant coating (enteric coating) is essential for this invention as pancreatin, a treatment for digestive disorders, is sensitive to gastric juices and the coating is required to get a good distribution of active agent (col 1, lns 13-30). However, Boedecker falls short of teaching the required plasticizer composition of the instant claims. Khanshab teaches that dibutyl phthalate is associated with toxicity issues, therefore it would have been obvious to avoid and/or replace with alternative plasticizer agents. Okumura teaches an enteric coating of a different active agent comprised of triethyl citrate and cetyl alcohol which can be included in amounts of around 7% by weight or higher, as required in the instant claims, and which teaches a superior sustained-release effect. The skilled artisan, concerned about the stability of pancreatin in the gastric juices, would be interested in a sustained-release or enteric coating as it would allow their active agent to survive the gastric juices prior to being fully released into the system. Moreover, with toxicity of dibutyl phthalate as a known issue, it would have been obvious to replace the plasticizer of Boedecker. Thus, the person of ordinary skill would look to Okumura for a gastroprotective coating free of monomeric phthalic acid esters and comprising triethyl citrate and cetyl alcohol and would have found it obvious to combine with or replace the enteric coating of Boedecker. Although Okumura teaches a process and a composition comprising theophylline, Mony teaches that pancreatin and theophylline are suitable replacements of each other in preparing a delayed release medicament. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07). Okumura teaches the enteric coating as suitable for preparing tablets with superior sustained-release profiles while Boedecker is interested in coating their micropellets so as to survive the traversal through the gastric juices. More generally, it would have been obvious to replace the dibutyl phthalate of Boedecker with the triethyl citrate and cetyl alcohol of Okumura due to known toxicity with the phthalate and the suitability of triethyl citrate and cetyl alcohol as plasticizing agents. Generally, it is prima facie obvious to substitute one equivalent component or process for another, each of which is taught by the prior art to be useful for the same purpose (see MPEP 2144.06).
The skilled artisan would have found it obvious to place the micropellet cores, which range from 0.7-1.4 mm, in an oral dosage form and use the composition to treat a medical condition, such as pancreatic exocrine insufficiency, as this is taught by the prior art.
Response to Arguments
Applicant's arguments filed 13 August 2025 have been fully considered but they are not persuasive. The Applicant argues, on pages 5-6 of their remarks, that Okumura teaches the plastic excipient in relation to the total composition and not in relation to the film forming agent.
In response, Okumura more broadly teaches the plastic excipient can be used in about 7% by weight based on including it in 10-50 parts in relation to 150 parts of enteric polymer agent. Therefore, Okumura teaches the range of concentrations as required in the instant claims.
The Applicant argues, on pages 6-7 of their remarks, that Khanshab is directed to pigmented ink formulations and not a pharmaceutical composition, and is thus not analogous art to the claimed invention.
In response, “A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention). Note that "same field of endeavor" and "reasonably pertinent" are two separate tests for establishing analogous art; it is not necessary for a reference to fulfill both tests in order to qualify as analogous art. See Bigio, 381 F.3d at 1325, 72 USPQ2d at 1212.” (See MPEP 2141.01(a)I) Because Khanshab teaches a health concern related to human contact with phthalate plasticizers, the reference can be considered “reasonably pertinent to the problem faced by the inventor.”
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 claims at issue 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 reference 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. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 53, 55, 58-63, and 66-69 are rejected on the ground of nonstatutory double patenting over claims 8-32 of U.S. Patent No. 9,198,871.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the ‘871 claims are narrower regarding some of the species and do not teach the triethyl citrate and cetyl alcohol in 7% by weight. The claimed micropellet core is taught in the claims of the ‘871 wherein the plasticizers are present in greater than 3% by weight relative to the film forming agent. The value of 7% is greater than 3% and is just included in the range of the ‘871 patent.
Claims 53, 55, 58-63, and 66-69 are rejected on the ground of nonstatutory double patenting over claims 7-101 of U.S. Patent No. 11,266,607 in view of Okumura et al. (US 6,426,091 B1).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the ‘607 claims are narrower regarding some of the species and do not teach the triethyl citrate and cetyl alcohol in 7% by weight. The claimed micropellet core is taught in the claims of the ‘101 wherein the plasticizers are present in greater but a weight is not disclosed. Okumura teaches using triethyl citrate and cetyl alcohol in 7% by weight in an enteric coating based on the broad teachings of how much plastic excipient and enteric polymer can be included, thus it would have been obvious to use 7% of the plasticizers in the enteric coating of ‘607.
Response to Arguments
Applicant's arguments filed 13 August 2025 have been fully considered but they are not persuasive. The Applicant argues, on pages 7-8 of their remarks, that Okumura does not teach triethyl citrate and cetyl alcohol in 7% by weight in relation to the film forming agent.
In response, Okumura more broadly teaches the plastic excipient can be used in about 7% by weight based on including it in 10-50 parts in relation to 150 parts of enteric polymer agent. Therefore, Okumura teaches the range of concentrations as required in the instant claims.
The Applicant argues, on pages 7-8 of their remarks, that the ‘871 claims do not specify the claimed range of plasticizer agents.
In response, ‘871 claims that the plasticizer agents “are collectively present in an amount greater than about 3% by weight relative to the one or more film forming agents” which includes any amount greater than 3% by weight, such as from 7-10% by weight.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW S ROSENTHAL whose telephone number is (571)272-6276. The examiner can normally be reached M-F 8-5pm EST.
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/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613