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 .
Status of the Application
Claims 1-2, 4-8, 11-14, 18-20, and 22-23 are pending
Claims 18-20 are withdrawn from examination as being drawn to a nonelected species.
Claims 1-2, 4-8, 11-14, and 22-23 are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/05/2024 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application claims benefit of U.S. Provisional Application No. 62/927,621 filed on 10/29/2019, U.S. Provisional Application No. 62/927,148 filed on 02/06/2020 and PCT Application No. PCT/US20/57784 filed on 10/28/2020.
Election/Restrictions
Applicant’s election without traverse of Group I and serine protease inhibitors in the reply filed on 07/29/2025 is acknowledged.
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/29/2025.
Claim Objections
Claim 7 is objected to because of the following informalities: “seroid” should be written as “steroid”. Appropriate correction is required.
Drawings
The drawings are objected to because claims 2, 4-5, and 22 recite Figures 5a to 5f, 6b, 6d, 7a, 7b, 7d, 7e, 8a-8e, 9a, 9b, 11e, 11f, 11g, 14a, 15m, 18a-18e, which are not legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 4, 5, and 11 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.
Claim 5 recites the limitation "the Bacteroides" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "claim 10" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claims 4 and 11 contain the trademark/trade name “Roche cOmplete EDTA-free protease inhibitor cocktail”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an EDTA-free protease inhibitor composition and, accordingly, the identification/description is indefinite.
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 1-2, 4-8, 11-14, and 22-23 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, "Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue', not 'experimentation'" (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations" (Wands, 8 USPQ2d 1404). Among these factors are: (i) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method of treating or preventing one or more of IBD, UC, or CD comprising administering a protease inhibitor. The breadth of the claims thus covers that any protease inhibitor is capable of preventing IBC, UC, or CD, which have different etiologies that are not completely understood.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
Torres et al. is drawn towards the prevention of inflammatory bowel disease (see abstract). Torres et al. teaches that “Increased evidence supports the concept of a preclinical phase in inflammatory bowel disease, preceding clinical diagnosis, during which immune and inflammatory pathways are already altered. As knowledge about this prediagnosis period expands, it unlocks the possibility of disease prediction and ambition for disease prevention and interception.” Id. Torres et al. teaches that “the full complexity of IBD remains to be uncovered and a prediction tool that can accurately identify individuals at high risk of developing disease still needs to be established and validated. Although it might be overly ambitious to envision preventing such a complex disease as IBD, such a strategy is already being explored in other immune-mediated diseases, such as type 1 diabetes (T1D) and rheumatoid arthritis, where disease prevention trials are currently ongoing.” (pg. 1454, left column, second paragraph). Torres et al. thus illustrates that there is not yet a known method of preventing IBD, and one of ordinary skill in the art would be unable to determine which protease inhibitors can prevent IBD without undue experimentation.
(5) The relative skill of those in the art:
Those of relative skill in the art are those with a level of skill of the authors of the references cites to support the examiner’s position (MD’s or those with advanced degrees and the requisite experience in medicine).
(6) The amount of direction or guidance presented and (7) the presence of absence of working examples:
The specification provides working examples only for the endoscopic assessment of patients with UC (see Example 2). Thus, the specification has not provided any working examples for the prevention of IBD, UC, or CD with any protease inhibitor.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by Torres et al. above, the high unpredictability in the art as evidenced therein, and the lack of adequate guidance provided by the specification for all TRPV1 agonists, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4, 8, 11-14, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Ruseler-van Embden et al. (US 6,723,354, as disclosed in IDS) in view of Paszti-Gere et al. (Interaction exists between matriptase inhibitors and intestinalepithelial cells, J. Enzyme Inhib. Med. Chem., 2016, 31(5), pp. 736-741) and Denadai-Souza et al. (Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease, Scientific reports, 2018, 8(1), pp. 1-9).
Ruseler-van Embden et al. teaches methods for treating or reducing inflammation by inhibiting proteolytic activity (see abstract). Ruseler-van Embden et al. teaches that “treatment is provided for an inflammation which is intestinal, perineal or peristomal, as is, for instance, seen with babies or infants with diaper rash, with children or adults with diarrhoea or fecal incontinence, with patients with inflammatory bowel syndrome and with stoma patients, which all suffer from the effects of proteolytic activity which is mainly fecal.” (col. 3, lines 21-27), which thus demonstrates a method of treating inflammatory bowel disease. Ruseler-van Embden et al. teaches “Fecal samples from twenty-seven patients with Chron's disease (CD) were studied. Twelve patients, aged 27-58 years, had undergone intestinal surgery 3---12 years previously; locations of the resections were terminal ileum, ileum and cecum, and colon. A second group of patients was not operated; the principal sites of inflammation were ileum, ileum and colon, and colon. The diagnosis CD was established with the usual clinical, radiological and histopathological criteria.” (col. 8, lines 33-41). Ruseler-van Embden et al. teaches providing treatment comprising administering a protease inhibitor (col. 3, lines 51-55), which target proteases caused by bacteria (col. 5, lines 29-37). Regarding claim 8, Ruseler-van Embden et al. teaches “Table 1 shows that patients with CD, ileostomy patients and patients with a pouch (with and without pouchitis) have a high proteolytic activity. “Regarding claims 11-13, Ruseler-van Embden et al. teaches that “Treatment of fecal proteolytic activity can occur by applying the inhibitor in an ointment, cream, gel, powder, or any other suitable form, to the perineal or peristomal location of the inflammation. Intestinal inflammations, such as seen with IBD or pouchitis, can be treated by rinsing the affected location in the digestive tract by, for example, administering an enema, or can be administered orally, preferably in a pharmaceutical composition such as a draught or mixture pill, that can pass relatively unaffected through the esophagus and stomach.” (col. 3, lines 29-37).
Ruseler-van Embden et al. does not teach administering a serine protease as the protease inhibitor.
Paszti-Gere et al. is drawn towards the effect of maltriptase inhibitors on intestinal epithelial function (see abstract). Paszti-Gere et al. teaches “In order to establish the role of serine protease activity in the maintenance of epithelial barrier integrity, firstly the non-selective enzyme inhibitor AEBSF was applied apically at 25 mM for a longer period of time on a IPEC-J2 cell monolayer. During the 1-day lasting withdrawal, serine protease activity seemed to start to recover after AEBSF administration… These findings in non-tumorigenic IPEC-J2 cells are in good agreement with previously published results where it was demonstrated that inhibition of matriptase non-selectively with water soluble AEBSF greatly suppressed TER development of Caco-2 cell layer.” (pp. 739-740, bridging paragraph).
Denadai-Souza et al. is drawn towards the profiling of serine proteases in inflammatory bowel disease (pg. 1, first paragraph). Denadai-Souza et al. teaches “in intestinal pathophysiological contexts such as inflammatory bowel disease (IBD), proteolytic homeostasis can be disrupted in tissues. Increased serine protease activity has been demonstrated in colonic tissues from Crohn’s disease (CD) or Ulcerative Colitis (UC) patients” (pg. 1, third paragraph).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to administer a serine protease inhibitor as the protease inhibitor, as suggested by Paszti-Gere et al. and Denadai-Souza et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Denadai-Souza et al. teaches that increased serine protease activity is present in IBD’s such as CD and UC, and Paszti-Gere et al. teaches AEBSF as an effective serine protease inhibitor that improves intestinal epithelial function (see abstract; pp. 739-740, bridging paragraph), with a reasonable expectation of success absent evidence of criticality of the particular steps.
Claims 5-6 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Ruseler-van Embden et al. (US 6,723,354, as disclosed in IDS), Paszti-Gere et al. (Interaction exists between matriptase inhibitors and intestinalepithelial cells, J. Enzyme Inhib. Med. Chem., 2016, 31(5), pp. 736-741), and Denadai-Souza et al. (Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease, Scientific reports, 2018, 8(1), pp. 1-9) as applied to claims 1-2, 4, 8, 11-14, and 23 above, and further in view of Fujita et al. (Quantitative analysis of bacterial DNA from Mycobacteria spp., Bacteroides vulgatus, and Escherichia coli in tissue samples from patients with inflammatory bowel diseases, Journal of Gastroenterology, 2002, 37, 509-516).
The teachings of Ruseler-van Embden et al., Paszti-Gere et al., and Denadai-Souza et al. above.
Ruseler-van Embden et al., Paszti-Gere et al., and Denadai-Souza et al. do not teach a protease expressed by the Bacteroides as recited in claims 5 and 6.
Fujita et al. is drawn towards an analysis of bacterial DNA in tissue samples from patients with inflammatory diseases (see abstract). Fujita et al. teaches that “B. vulgatus and E. coli were detected more frequently and in greater numbers in samples from patients with inflammatory bowel diseases than in samples from control patients with colon cancer… B. vulgatus and E. coli are not a direct cause of inflammatory bowel diseases, although they may contribute to the diseases by preventing or delaying remission.” (see abstract).
It would have been obvious to one of ordinary skill in the art to target a protease expressed by one or both of Bacteroides vulgatus and Bacteroides dorei, as suggested by Fujita et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Fujita et al. teaches that Bacteroides vulgatus may contribute to inflammatory bowel disease by preventing or delaying remission (see abstract), with a reasonable expectation of success absent evidence of criticality of the particular steps.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Ruseler-van Embden et al. (US 6,723,354), Paszti-Gere et al. (Interaction exists between matriptase inhibitors and intestinalepithelial cells, J. Enzyme Inhib. Med. Chem., 2016, 31(5), pp. 736-741), and Denadai-Souza et al. (Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease, Scientific reports, 2018, 8(1), pp. 1-9) as applied to claims 1-2, 4, 8, 11-14, and 23 above, and further in view of Kozuch (Treatment of inflammatory bowel disease: A review of medical therapy, World Journal of Gastroenterology, 2008, 14(3), pp. 354-377).
The teachings of Ruseler-van Embden et al., Paszti-Gere et al., and Denadai-Souza et al. above.
Ruseler-van Embden et al., Paszti-Gere et al., and Denadai-Souza et al. do not teach further administering a non-specific immunosuppressive agent, such as a steroid.
Kozuch is drawn towards various treatment for inflammatory bowel diseases (pg. 354, Introduction). Kozuch teaches that “Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; nonsystemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease.” (see abstract).
It would have been obvious to one of ordinary skill in the art to further administer a non-specific immunosuppressive agent, such as a steroid, as suggested by Kozuch, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since it is prima facie obvious to combine components known for the same purpose for their combined additive effects, with a reasonable expectation of success absent evidence of criticality of the particular formulation. Additionally, “[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Therefore, it would have been prima facie obvious to combine a protease inhibitor and a steroid in a composition cojointly to treat inflammatory bowel disease.
Conclusion
1-2, 4-8, 11-14, and 22-23 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691