DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Preliminary Amendments filed on July 20, 2023, January 24, 2024 and November 5, 2025, have been received and entered.
3. Applicant’s election without traverse of Group I on November 11, 2025, is acknowledged.
Claim Disposition
4. Claims 2, 8, 12, 17-19, 21-23, 26-27, 29-30, 36-39 and 41-46 have been cancelled. Claims 1, 3-7, 9-11, 13-16, 20, 24-25, 31-35, 40 and 47-50 are pending. Claims 1, 3-7, 9-11, 13-16, 20, 24-25, 31-35, 40 and 47-49 are under examination. Claim 50 is withdrawn from further consideration pursuant to 37 CFR 1.12(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Information Disclosure Statement
5. To date no Information Disclosure Statement has been filed. Applicant is reminded of the duty to disclose.
Drawing
6. The drawings filed on July 20, 2023, have been accepted by the examiner.
Specification Objection
7. The specification is objected to for the following informalities:
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following is suggested: "A method for separating and analyzing pancreatic enzymes".
Appropriate correction is required.
Claim objection
8. Claims 13-21 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to recite “…..and/or’ [[or/and]]…”. For clarity it is suggested that claim 1 is amended to read, “A method for separating and analyzing pancreatic enzymes [[present]] in a [[pharmaceutically acceptable]] pancreatic protein mixture…..” (see pages 1-2 of the specification). The dependent claims hereto are also included.
For clarity it is suggested that claims 1, 16, 31, 33-35 and 48-49 are amended to delete the word “suitable”.
For clarity it is suggested that claims 3-7, 9-11, 13-16, 20, 24-25, 28, 31-35, 40, 47-49 are amended to recite, “of” instead of “according to” (for example, “The method of claim 1….”).
For clarity and precision of claim language it is suggested that claims 3-5 and 7 are amended to delete the phrase, “pharmaceutically acceptable’’.
For clarity it is suggested that claim 3 is amended to recite, “…microbially synthesized……”.
Claim 4 is objected to under 37 CFR 1.75(c), as being of improper dependent form for failing to further limit the subject matter of a previous claim. Applicant is required to cancel the claim(s), or amend the claim(s) to place the claim(s) in proper dependent form, or rewrite the claim(s) in independent form. Claim 4 is substantially the same as independent claim 1.
For clarity it is suggested that claims 1, 6-7 and 9-11 are amended to spell out the acronyms.
For clarity it is suggested that claim 13 is amended to define the improvement.
For clarity it is suggested that claim 16 is amended to recite, “…wherein the solvent is further….”.
For clarity it is suggested that claim 20 is amended to read, “….the organic solvent comprises acetonitrile…….0.3%; [[or]]
the organic solvent comprises acetonitrile…….about 0.3%; or
the organic solvent comprises acetonitrile…….”.
Appropriate correction is required.
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.
9. Claims 1, 3-7, 9-11, 13-16, 20, 24-25, 31-35, 40 and 47-49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph, as failing to comply with the written description requirement. 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.
The claimed invention is directed to “a method for separating and analyzing pancreatic enzymes…” (see claim 1 in its entirety). MPEP 2111.01 states that “during examination, the claims must be interpreted as broadly as their terms reasonably allow”. The invention as claimed broadly encompasses any amylase, lipase and protease in the pancreatic protein mixture. However, the specification and dependent claims are directed to:
“ In an embodiment, the pancreatic sample comprises enzyme selected from Triacylglycerol lipase, Co-lipase, CEL lipase, Phospholipase A2, Trypsin, Chymotrypsin, Elastase, Carboxypeptidase A1, Carboxypeptidase B, Kallikrien glandular, and Alpha amylase are the prominent functionally”. The claimed invention encompasses a large variable genus of the enzymes or variants thereof claimed and not limited to the aforementioned ones (see instant claim 11). The claimed invention is directed to a “pharmaceutically acceptable” pancreatic protein mixture and does not define what is intended. Dependent claim 3 recites that the pharmaceutically acceptable pancreatic protein mixture is obtained from crude, partially purified, substantially purified and microbially synthesize pancreatic sample. The art generally recognizes that pharmaceutically acceptable refers to ingredients, salts, or carriers that are safe, non-toxic, and suitable for human or animal use, maintaining a positive benefit/risk ratio without causing undue irritation or allergic responses. It ensures the substance is compatible with the active drug, chemically stable, and meets regulatory standards like GMP. The specification discloses on two occasions that “the invention provides a pharmaceutically acceptable pancrelipase protein” and “In an embodiment, the invention provides a pharmaceutically acceptable pancreatic protein mixture comprising one or more enzyme selected from amylase, lipase and protease”. However there is no indication in the specification what is intended by a pharmaceutically acceptable pancreatic protein mixture and the method in independent claim 1 does not have any steps to obtain such a product. In fact, the specification discloses that, “in certain embodiment, the pancreatic protein mixture is obtained from crude, partially purified and substantially purified and microbially synthesize pancreatic protein sample”. Thus the claimed invention is not adequately described.
Furthermore, the claimed invention is directed to the claimed method for ‘improving batch to batch consistency’, which is repeated in the specification a few times however there are no indicia as to how much improvement or how it’s improved. Additionally the claimed invention includes a large genus of suitable reducing agents. Thus the claimed invention is not adequately described.
The claimed invention is not commensurate in scope with the disclosure. The specification fails to provide a representative number of species for the claimed genus to show that applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described, are representative of the entire genus.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by
functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
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.
10. Claim 48 is 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 48 is rejected as being indefinite because it recites ‘suitable reducing agent” because it is unclear what is considered to be ‘suitable”. Further, the specification does not provide a standard to determine what is suitable.
In addition, the protein mixture is directed to any amylase, protease and lipase thus unclear what specific one in each category to determine “the suitable reducing agent”.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
11. Claim(s) 1, 3-7, 14, 16 and 33 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Europroteome AG (WO 2004/102189, of record in the application).
The primary reference is directed to a method for separating and analyzing pancreatic enzymes present in pancreatic protein mixture (methods for the differential diagnosis of pancreatitis and pancreatic cancer by detecting one or more differentially expressed biomolecules within a test sample of a given subject, (see page 4, lines 9-11) comprising: a. preparing the soluble protein mixture from pancreatic sample (test sample of a given subject, (see page 4, lines 9-11); b. loading the soluble protein mixture onto SE-HPLC column (comprising columns for High Pressure Liquid Chromatography, HPLC, (see page 20, lines 19-20; where separation of a biomolecule from other biomolecules within a given sample for the purpose of enrichment, purification and or analysis, may be achieved by size exclusion chromatography, (see page 13, lines 19-22); c. treating the SE-HPLC column with suitable separating solution in mobile phase selected from buffer or/and organic solvent (where washing solution or eluents {are} used to wash the unbound biomolecules from a biologically active surface, (to) include organic solutions, aqueous solutions such as buffers, wherein a buffer may contain reducing agents in appropriate concentrations as those known to those skilled in the art, (page 33,line 29-32; wherein biomolecules are eluted from the biologically active surface by washing the vessel with appropriate solutions known to those skilled in the art,(see page 31, line 19-20); d. eluting the pancreatic enzyme based on their molecular weight (wherein biomolecules are eluted from the biologically active surface by washing the vessel with appropriate solutions known to those skilled in the art,(see page 31, line 19-20; where the phrase 'differentially present biomolecule' refers to the quantity biomolecule [of a particular apparent molecular mass] present within a sample taken from a subject, as compared to a comparable sample, (page 11, page 29-31); e. analyzing the eluted pancreatic enzyme comprising at least one enzyme selected from amylase, and lipase (comprising obtaining the quantity of a biomolecule [of a particular apparent molecular mass] present within a sample taken from a subject, as compared to a comparable sample, (see page 11, page 29-31; wherein serum concentrations of amylase and lipase {are} the most commonly measured pancreatic enzymes,(page 2, line 8-9).
Europroteome discloses that the pancreatic protein mixture is obtained from crude, partially purified, substantially purified sample (separation of a biomolecule from other biomolecules within a given sample for the purpose of enrichment, purification and or analysis, may be achieved by size exclusion chromatography, (see page 13, line 19-22). The reference further discloses wherein the method provides analysis
of pancreatic protein mixture comprising an enzyme selected from amylase, lipase and combination thereof (comprising obtaining the quantity of a biomolecule [of a particular apparent molecular mass] present within a sample taken from a subject, as compared to a comparable sample, (page 11, page 29-31; wherein serum concentrations of amylase and lipase {are} the most commonly measured pancreatic enzymes, (see page 2, line 8-9). The limitation of the enzymes being amylase, lipase and combinations thereof is taught by the reference (comprising obtaining the quantity of a biomolecule of a particular apparent molecular mass present within a sample taken from a subject, as compared to a comparable sample, (see page 11, pages 29-31; wherein serum concentrations of amylase and lipase (are) the most commonly measured pancreatic enzymes, (see page 2, lines 8-9).
The reference also teaches that the method provides analysis of the pancreatic protein mixture comprising a low molecular weight and high molecular weight impurities of pancreatic enzyme selected from amylase, lipase and combination thereof (where separation of a biomolecules from other biomolecules within a given sample for the purpose of enrichment, purification and or analysis, may be achieved by…… Size exclusion chromatography,(see page 13, lines19-22);(comprising obtaining the quantity of a biomolecule (of a particular apparent molecular mass) present within a sample taken from a subject, as compared to a comparable sample,(see page11, pages 29-31); wherein serum concentrations of amylase and lipase are the most commonly measured pancreatic enzymes(see page 2, line 8-9). Moreover the reference teaches analysis or quantification is performed by the method selected from SDS-PAGE, MALDI-TOF-MS, SE-HPLC (using matrix assisted laser the sorption ionization (MALDI), mass spectrometry… Wherein the sample is partially purified to obtain a fraction that essentially consist of a marker using separation methods such as two dimensional gel electrophoresis or high performance liquid chromatography, HPLC, (see page 34, lines 29-33) comprising columns for… High pressure liquid chromatography, HPLC, (see page 20, lines 19-20); where separation of a biomolecules from other biomolecules within a given sample for the purpose of enrichment, purification and or analysis, may be achieved by… Size exclusion chromatography; and amylase and lipase most commonly measured (see page13, lines 29-22 and page 2, lines 8-9).
It is also disclosed that the organic solvent selected from ACN, TFA and mixtures thereof to form suitable separating solution in mobile phase 50% ACN and 0.5% Trifluoroacetic acid was applied to the spots (see page 47, line 6). The reference also teaches that the organic solvent is further used in combination with aqueous solution to form suitable separating solution in mobile phase(biological samples in the aqueous form can be further prepared using specific solutions for denaturation(pretreatment like …mercaptoethanol (see page 32, lines 20-21 and page 47, line 6).
Therefore, the limitations of the claims are met by the reference.
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.
12. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
13. Claim(s) 1, 3-4, 6-7, 24-25 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Qingdao (CN 103667225 ) in view of Zhejiang (CN 103405756) and Wezeman (US Patent No. 9,291,630) taken with Sanger-van de Griend (Electrophoresis. 2019 Sep;40(18-19):2361-2374) and Yang (2015, Journal of Pharmaceutical and Biochemical Analysis 109:52-61).
Qingdao discloses a process for an extraction of pancreatic protein from pancreatic protein sample, elastase from animal pancreas (abstract), comprising (a) treating the pancreatic protein sample with a bicarbonate (carbonic acid) buffer at any pH, (b) dissolving the pancreatic protein sample in the carbonic acid buffer, and (c) colleting the pancreatic protein, elastase (page 2, “Summary of the invention” and claim 4). The process of Qingdao is an improvement compared to the conventional extraction process that does not use a bicarbonate buffer (page 1, “Background Technology”) and comprises dissolving the pancreatic protein sample by stirring by stirring (page 2, “Summary of the invention”). Qingdao discloses that elastases are used as a pharmaceutical (page 1, “Background Technology”). Therefore, the elastase prepared from the process of Qingdao is a pancreatic protein that is a pharmaceutically acceptable protein. Qingdao does not disclose using a citrate-phosphate buffer at the recited concentration and pH, bicarbonate at the recited pH. Qingdao discloses adjusting the pH to 6.0-9.0 (page 2, “Summary of the invention”). However, Qingdao discloses using phosphoric acid buffers (page 2, “Summary of the invention” and claim 4). In-so-far-as Qingdao is silent on the citrate-phosphate buffer, this is known in the art. Zhejiang discloses using a citrate-phosphate buffer at a concentration of 100mM to prepare a pancreatic protein (pages 3-4, “The preparation of embodiment 1 pancreatin”). In terms of analysis, Wezeman discloses estimation and/or quantification of pancreatic proteins using SDS-PAGE to determine the molecular weight of the pancreatic protein (Column 6, lines 1-14) and using RP-HPLC to the purify the pancreatic protein (Column 4, lines 45-64). Further, CE-SDS was also known in the art as an alternative to SDS-PAGE, as disclose by Sanger-van de Griend (abstract and page 2631, “Introduction”). Additionally, SE-HPLC was also known in the art to purify proteins based on size, as disclosed by Yang (abstract and page 52, right column).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claimed invention as obvious. In combining the teachings Qingdao and Zhejiang, it would have been obvious to one having ordinary skill in the art to modify the process of Qingdao by substituting the phosphoric acid buffer with citrate-phosphate buffer, stirring the pancreatic protein the buffer at 200 rpm for 30 minutes, and optimize the pH of the citrate-phosphate buffer and/or bicarbonate buffer. One of ordinary skill in the art at the time the invention was made would have been motivated to make the modifications in order to further improve the extraction and preparation of the pancreatic protein. One of ordinary skill in the art would have had a reasonable expectation of success since Qingdao teaches a process for the extraction and preparation of a pancreatic protein by dissolving the pancreatic protein sample in a bicarbonate buffer and phosphoric acid buffer and Zhejiang teaches using a citrate-phosphate buffer for the preparation of a pancreatic protein.
In combining the teachings Qingdao, Wezeman, Sanger-van de Griend, and Yang, it would have been obvious to one having ordinary skill in the art to modify the process of Qingdao by purify the elastase using RP-HPLC or SE-HPLC and/or determine the molecular weight of the elastase using SDS-PAGE or CE-SDS. One of ordinary skill in the art at the time the invention was made would have been motivated to make the modifications in order to purify the elastase and determine the molecular weight of the elastase. One of ordinary skill in the art would have had a reasonable expectation of success since Qingdao teaches a process for the extraction and preparation of a pancreatic protein by dissolving the pancreatic protein sample in a bicarbonate buffer and phosphoric acid buffer, use of RP-HPLC and/or SE-HPLC to purify proteins were known in the art, and use of SDS-PAGE, and CE-SDS to determine the molecular weights of proteins were known in the art.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Basis For NonStatutory Double Patenting
14. 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. See 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
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).
15. Claims 1, 3-4, 6-7, 24-25 and 28 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1, 8, 12, 15, 29, and 34-39 of Copending Application 18/262316, in view of Wezeman (teaching set forth above). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The present claims 1, 3-4, 6-7, 24-25 and 28 drawn to a method for separating and analyzing pancreatic enzymes present in a pharmaceutically acceptable pancreatic protein mixture, such as amylase, protease and lipase enzymes. Claims 1, 8, 12, 15, 29, and 34-39 of Copending Application 18/262316 are directed to a process for an extraction of pancreatic protein from a pancreatic protein sample which comprises the use of a buffer solution and the enzymes lipase, protease and amylase using CE-SDS, SDS-PAGE and SE-HPLC. Thus, the active ingredient and method steps in the present claims and the claims of the copending application are very similar. The copending claims teach estimation and quantification performed for example with, SE-HPLC or SDS-PAGE, and references such as Wezeman discloses estimation and/or quantification of pancreatic proteins using SDS-PAGE. Therefore, although the scope of the claims vary slightly, they are obvious variations of each other. The conflicting claims are not patentably distinct from each other, thus prima facie obvious.
Conclusion
16. No claims are presently allowable.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652