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 .
Claims 1-20 are pending in this application, Claims 13-20 are acknowledged as withdrawn.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/31/2023 has been entered.
The rejection of at least claim 1 is rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-4 and 6 of co-pending US application No. 14/906,613 has been withdrawn due to the abandonment of the ‘613 application.
Election/Restrictions
Applicant’s election without traverse of Group II (Claims 1-12) and of the species (organic solvent: acetone) in the reply filed on 12/22/2025 is acknowledged.
Claims 1-12 were examined on their merits.
Specification
The use of the term SEPHADEX™, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 6 is objected to because of the following informalities: A comma should be inserted between “dimethylsulfoxide” and “butylalcohol”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-12 are rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The term “high activity” in claim 1 is a relative term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claims 2-12 are rejected as being dependent upon rejected Claim 1.
Claim 1, step a1.1 recites “an aqueous solvent”. It is unclear if this recitation is the same as or distinct from the “solvent having a Hildebrand solubility parameter between 34-39 (MPa)0.5, wherein the solvent is a mixture of at least one organic solvent and an aqueous solvent” recited in the preamble of Claim 1 and step a1. For purposes of examination the Examiner has interpreted the solvents as being distinct.
Claim 3 recites the limitation “the solvent”. It is unclear which solvent is being referred to as Claim 1 recites “a mixture of at least one organic solvent and an aqueous solvent”, an “an aqueous solvent” and “at least one organic solvent”.
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.
Claim(s) 1-8 are rejected under 35 U.S.C. § 103 as being unpatentable over Schultze (US 4,263,624) in view of Hwang et al. (2007), of record.
Schultze teaches an aqueous pancreas (inherently comprising pancreatin) tissue suspension stirred in an aqueous solvent (calcium gluconate and water buffer) (Column 7, Lines 3-7 and Column 8, Claim 1);
adding to the pancreatin suspension the organic solvent isopropyl alcohol/isopropanol at a pH of from 6.5 to 7.5 (Column 3, Lines 31-35) at a temperature of 20 °C or below 30 °C (reading on the claimed temperature ranges of below 20 °C and 4 °C) to precipitate an insoluble from soluble portion (Column 7, Lines 15-21 and Column 8, Lines 6-0 and 22-23 and Claim 1);
separating the insoluble precipitate from the supernatant at 20 °C and drying the obtained insoluble precipitate (Column 8, Lines 22-38) to yield a pancreatin comprising protease, amylase and lipase with a specific lipase activity of 90.3 FIP-U/mg, and reading on Claims 1, steps a1)-a3), 2, 6 and 8.
With regard to Claim 3, the reference teaches suspension of the pancreatin in calcium gluconate/sodium bicarbonate aqueous solvent (autolysis) for 30 minutes (Column 7, Lines 57-64) or for 1-4 hours (within the claimed range of about ten to about sixty minutes) (Column 7, Lines 41-53).
With regard to Claim 4, the reference teaches mixing 1kg of pancreatin with 5 L of water (solvent) (1kg/5L = 0.2kg/L =0.2 g/mL) (within the claimed range of about 0.050-0.3 g/mL).
With regard to Claim 7, the reference teaches acetone may be used instead of isopropyl alcohol (Column 3, Lines 66-68).
The Schultze reference does not teach a method wherein the solvent has a Hildebrand solubility parameter between 34-38 (MPa)0.5, or wherein the recovered pancreatin has a specific lipase activity of at least 120 USP IU/mg, as required by Claim 1;
wherein the aqueous solvent has a pH of about 4.0, as required by Claim 5.
Hwang et al. teaches that pancreatin proteins can be selectively precipitated using organic solvents wherein pancreatin solubility as a predictor was found to agree well with the solution polarity, expressed in terms of the Hildebrand solubility parameter (Pg. 4289, Abstract) and provides the Hildebrand solubility parameter values for water and various organic solvents at 25 °C (Pg. 4390, Table 1).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of extracting pancreatin using an aqueous solvent comprising an organic solvent to use a solvent having a Hildebrand solubility parameter value in the claimed range because Hwang et al. teaches that pancreatin solubility correlates with the solution polarity, expressed in terms of the Hildebrand solubility parameter. Hwang et al. teaches the solubility parameter values of various organic solvents (Pg. 4390, Table 1) wherein water is 47.9 (MPa)0.5 and acetone is 20.2 (MPa)0.5 at 25 °C. These are endpoints in a useful concentration range which encompasses the claimed range of 34-38 (MPa)0.5.
This is motivation for someone of ordinary skill in the art to practice or test the solvent solubility parameter values widely to find those that are functional or optimal to sufficiently solubilize pancreatin which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the solvent solubility parameter in the process, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a solvent solution with the desired solubility with respect to pancreatin. There would have been a reasonable expectation of success in making these modifications because all of the references are reasonably drawn to the same field of endeavor, that is, organic solvents and pancreatin extraction.
While the references listed above do not specifically teach the limitation of Claim 5, that the aqueous solvent has a pH of about 4.0, one of ordinary skill in the art would recognize that the pH of an aqueous solvent in a composition is a result-effective optimizable variable. Schultze teaches adding to the pancreatin suspension the organic solvent isopropyl alcohol/isopropanol at a pH of from 6.5 to 7.5 (Column 3, Lines 31-35). These are starting points for the determination of a useful solvent pH range. This is motivation for someone of ordinary skill in the art to practice or test the aqueous solvent pH parameter values widely to find those that are functional or optimal to sufficiently extract/precipitate desired pancreatin.
Absent any teaching of criticality by the Applicant concerning the pH of the aqueous solvent in the composition, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain an aqueous solvent solution with the desired pH with respect to extraction/precipitation of pancreatin. There would have been a reasonable expectation of success in making these modifications because all of the references are reasonably drawn to the same field of endeavor, that is, organic solvents and pancreatin extraction.
Claim(s) 1-8 and 9-12 are rejected under 35 U.S.C. § 103 as being unpatentable over Schultze (US 4,263,624) in view of Hwang et al. (2007), of record, as applied to Claims 1-8 above, and further in view of Cordwell et al. (2008).
The teachings of Schultze and Hwang et al. were discussed above.
Neither reference taught a method wherein steps a.1-a.3 are performed on the soluble portion after separation of the insoluble portion, as required by Claims 9-12.
Cordwell et al. teaches that sequential extraction of proteins uses different solubilities of proteins allowing them to be extracted in a series of progressively harsher extraction reagents.
In the first step, highly soluble proteins are extracted with 40 mM Tris-HCl buffer (pH 7.8). Proteins solubilized in this extraction are precipitated and resolubilized in a 2-DE-compatible sample buffer. Identification of these proteins generally reveals that they are cytoplasmic in subcellular location and are often key metabolic enzymes involved in critical processes such as glycolysis, the tricarboxylic acid cycle, as well as chaperonins, translation factors, and ribosomal proteins. The insoluble pellet from this step is then washed extensively and resolubilized with a standard 2-DE sample buffer containing 5–8 M urea and 2% (w/v) 3-[(3- Cholamidopropyl)dimethylammonio]-1- propanesulfonate (CHAPS) as the detergent (Pg. 140, Lines 18-29).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of a single round of extracting pancreatin using an aqueous solvent of Schultze to perform a second round of extraction on the produced first soluble portion as taught by Cordwell et al. because this would allow further precipitation and solubilization of proteins which were not extracted in the first extraction. Those of ordinary skill in the art would have been motivated to make this modification in order to increase yield of pancreatin and/or to extract pancreatin which requires different solvent solubility. There would have been a reasonable expectation of success in making this modification because both references are drawn to the same field of endeavor, that is, extraction and solubilization of desired proteins.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159.
See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 3-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-12, 14, 17 and 18 of copending Application No. 18/975,950 (reference application) as evidenced by Oxford English Dictionary (2026). Although the claims at issue are not identical, they are not patentably distinct from each other because instant Claim 1 is drawn to a process for the preparation of a high activity pancreatin having specific lipase activity of at least about 120 USP IU/mg wherein the pancreatin is of mammalian origin and comprises lipase, protease and amylase, the process comprising treating mammalian pancreatin with a solvent having a Hildebrand solubility parameter between about 34 to 38 (MPa)0.5, wherein the solvent is a mixture of at least one organic solvent and an aqueous
solvent, the process comprising the steps of:
a1) suspending pancreatin in the mixture of at least one organic solvent and an aqueous solvent at a temperature below 20 °C to provide a suspension comprising an insoluble portion and a soluble portion;
and recovering the high activity pancreatin comprising lipase, protease and amylase and having a specific lipase activity of at least 120 USP IU/mg.
This is made obvious by obvious by Claims 8 and 12 of the copending ‘950 application drawn to:
A process for the preparation of HA-pancreatin having specific lipase activity of at least about 120 USP IU/mg, comprising treating pancreatin with a solvent having Hildebrand solubility parameter comprised between 28 and 45 (MPa)⁰⁵, wherein said solvent is one organic solvent or a mixture of organic solvents or a mixture of at least one organic solvent and aqueous solvent, and the process temperature is below room temperature;
wherein the solvent is a mixture of at least one organic solvent and aqueous solvent and wherein step al comprises the following steps:
a1.1) suspending pancreatin in aqueous solvent under stirring;
a1.2) adding to the suspension of step la the one organic solvent or mixture thereof; and wherein the process temperature is below room temperature.
Oxford English Dictionary evidences that “room temperature” is conventionally taken as about 20 °C. Thus, the ordinary artisan would recognize that the “below room temperature” limitation of the ‘950 would be sufficiently close to read on the “below 20 °C” limitation of the instant ‘488 application.
While the ‘950 application does not indicate that the pancreatin is mammalian, those of ordinary skill in the art would recognize that pancreatin is only obtainable from mammals and non-mammals and the selection thereof would have been a matter of artisan preference and/or availability.
Instant claims 3, 4, 5, 6 and 7 correspond to Claims 14,12, 19 and 17 of the copending ‘950 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments, see Remarks, filed 07/31/2023, with respect to the above withdrawn rejection have been fully considered and are persuasive. The Applicant’s remarks have been considered only insofar as they apply to the current rejections herein.
Applicant’s arguments with respect to the rejection based on the Moreau reference have been considered but are moot because the new ground of rejection does not rely on that reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant's arguments filed 07/31/2023 have been fully considered but they are not persuasive.
The Applicant argues that Hwang teaches that lipase precipitation does not depend on its solubility in solution and that pancreatin precipitation is maximized below 28 (MPa0.5). Applicant notes the claimed solvent solubility parameter was preferred, even though Hwang does not teach a change in lipase precipitation in the claimed range. Applicant concludes that it would not have been obvious (or with a reasonable expectation of success) to optimize the solubility parameter of the solvent to obtain the claimed pancreatin product as Hwang teaches lipase precipitation is independent of solvent solubility (Remarks, Pg. 6, Lines 22-29 and Pg. 7, Lines 1-25).
This is not found to be persuasive for the following reasons, while Hwang may teaches that lipase precipitation does not depend on its solubility in solution, the reference does teach that pancreatin (a mixture of lipase, protease and amylase) solubility is correlated with solution polarity, expressed in terms of the Hildebrand solubility parameter. Further, Figure 6 of Hwang indicates that protein precipitates remain optimal at solubility parameters up to 34 (MPa0.5). The Examiner maintains that
Hwang et al. teaches that pancreatin solubility correlates with the solution polarity, expressed in terms of the Hildebrand solubility parameter. Hwang et al. teaches the solubility parameter values of various organic solvents (Pg. 4390, Table 1) wherein water is 47.9 (MPa)0.5 and acetone is 20.2 (MPa)0.5 at 25 °C. These are endpoints in a useful concentration range which encompasses the claimed range of 34-38 (MPa)0.5.
This is motivation for someone of ordinary skill in the art to practice or test the solvent solubility parameter values widely to find those that are functional or optimal to sufficiently solubilize pancreatin which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the solvent solubility parameter in the process, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). There would have been a reasonable expectation of success in making these modifications because all of the references are reasonably drawn to the same field of endeavor, that is, organic solvents and pancreatin extraction.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 01/14/2026