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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 2, 4-10 and 12, in the reply filed on 3 December 2025 is acknowledged.
Applicant’s election without traverse of the species of self-assembling peptide (SEQ ID NO: 1) and the species of active agent (Tofacitinib) in the reply filed on 3 December 2025 is acknowledged.
Claims 13-19 are withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 3 December 2025.
Claim 11 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3 December 2025.
Claims 1, 2, 4-10 and 12 are under consideration.
Status of Claims
The claim listing filed 3 December 2025 is pending. Claim 3 is cancelled. Claims 11 and 13-19 are withdrawn from further consideration for the reasons set forth above, 37 CFR 1.142(b). Claims 1, 2, 4-10 and 12 are being examined on the merits in this office action.
Priority
The present application claims benefit under 35 U.S.C. 119(e) to U.S. Provisional Application Nos. 63/342,081 filed 14 May 2022, and 63/412,464, filed 2 October 2022. Applicants claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365 (c) is acknowledged.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 8/26/2023, 1/14/2024, 1/1/2025, and both IDS submitted on 1/8/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
Claims 1, 2, 4-10 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a composition for oral administration for treatment of gastrointestinal (GI) diseases associated with chronic inflammation of the GI tract, does not reasonably provide enablement for the treatment of all gastrointestinal disease or injury in a subject. The claims contain 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. This is a scope of enablement rejection.
The test for enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d (Fed. Cir. 1988). Whether undue experimentation is required is not based upon a single factor, but rather is a conclusion reached by weighing many factors (see Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include, but are not limited to:
The breadth of the claims;
The nature of the invention;
The state of the prior art;
The level of one of ordinary skill;
The level of predictability in the art;
The amount of direction provided by the inventor;
The existence of working examples; and
The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The relevant factors are addressed below on the basis of comparison of the disclosure, the claims, and the state of the prior art in the assessment of undue experimentation.
The nature of the invention is directed to a composition for oral administration for treatment of gastrointestinal disease or injury of a subject, said composition comprising: nanoemulsion particles (NEs) comprising a hydrophobic liquid core, and at least one hydrophobic surfactant (S1) and at least one hydrophilic surfactant (S2) in the external layer, said surfactants being nonionic polar surfactants surrounding the core; wherein the liquid core comprises one or more therapeutically active agent(s);and wherein the NEs are combined with a self-assembling peptide. The direction and guidance stated in the specification is based on bowel diseases associated with inflammation and their treatment. That is, in order to be fully enabled to practice the full scope of the claimed invention, the skilled artisan would have to accept that all gastrointestinal diseases and injuries are associated with inflammation of the GI tract. The claim is broad and inclusive of every gastrointestinal disorder or injury. The breadth of the claim exacerbates the nature of the subject matter to which the present claims are directed. Each GI disease, including those detailed in the specification, have several subcategories that each have unique physiological characteristics and treatment methods.
The state of the prior art and the level of predictability is low but predictable. While the state of the art in regard to the treatment of specific GI diseases is high, the start of the art in regard to treating all GI diseases with a single method is underdeveloped. Particularly, there is no known treatment that in effective against all gastrointestinal disorders. Art on gastrointestinal disease treatment has a very high level of predictability, when the diseases are grouped based on like characteristics. Ford teaches that while individuals with Irritable Bowel Syndrome (IBS) and IBD may present the same, or similar, symptoms (due to the GI tract being able to express only a limited amount of symptoms), the two have different hallmark indicators, for instance, mucosal inflammation and fecal calprotectin can be seen in IBD, while IBS is a functional disorder with no biomarker (Page 221, “The gastrointestinal tract has a limited repertoire of symptoms … the symptoms of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) can overlap … The hallmark indicator of IBD is an actual visible mucosal inflammation seen at colonoscopy or cross-sectional imaging. IBD also has well-accepted biomarkers, including fecal calprotectin, whereas IBS is a functional disorder with no accepted biomarker or structural explanation seen at colonoscopy for the symptoms”. Singh et al teaches that there is significant variation in the treatment of inflammatory bowel disease (IBD) provided by GI physicians, due to IBD encompassing a group of complex disorders, spanning from ulcerative colitis to Crohn’s disease ([Introduction] “Inflammatory bowel disease (IBD) is a group of chronic complex immune-mediated disorders of the gastrointestinal tract that affects over a million patients in the USA. IBD spans a spectrum that includes ulcerative colitis (UC) and Crohn’s disease (CD) at two ends and indeterminate/undefined disease in between.”, [Discussion] “Managing patients with IBD is challenging because of multiple factors. These include a complex disease spectrum, varied clinical presentation and rapidly changing treatment options. Although the overall success rate of treatment has improved, the understanding of the risks and benefits of available treatment options continues to evolve. There are wide variations in treatment patterns and varied adherence to existing recommendations. Recognition of the variations is one of the first steps to help improve care and outcomes.”). The prior art does not show all GI diseases being treated using the same methods, despite them having similar symptoms.
The amount of direction provided by the inventors and existence of working examples is minimal. It has been established that "the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art." In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970). Applicant fails to present specific guidance on how treatment of all GI disorders can be achieved by administering the composition as described in the instant invention. Applicant shows that in mice with induced colitis, the administration of PURASTAT-Tofacitinib loaded nanoemulsion (PS_NE_TFC) results in an improvement in the disease activity index (DAI) ([para. 0087 of the PGPUB] “These results indicate that that MPO activity was lower in colonic tissue from IBD mice treated with PS_NE_TFC particularly when compared the G3 mice treated with plain TFC.” [para. 0088 of the PGPUB] “Exemplary histological results of colon tissue stained with HPS are shown in Figures 13 through 18 for mice from the different groups as indicated. Macroscopic results from the study are plotted in Figure 9. As shown more clearly in Figure 10, the mice treated with TFC-loaded nanocomposite showed a statistically significant improvement in DAI score relative to the other treated groups on day 7 and day 8 of the study”). The ability for PS_NE_TFC to decrease in DAI score in DSS induced colitis in mice cannot be used as proof that PS_NE_TFC can be used to treat GI diseases, as colitis is not representative of all GI disease types. Colitis cannot model the specific characteristics found in the various different GI diseases the instant invention claims to treat, as shown by Qin (“Why is damage limited to the mucosa in ulcerative colitis but transmural in Crohn’s disease?”, World J Gastrointest Pathophysiol 2013; 4(3): 63-64 [PMID: 23946890 DOI: 10.4291/wjgp.v4.i3.63]). Qin shows that the inflammation associated ulcerative colitis is limited to the mucosa, while Crohn’s disease inflammation is transmural and can be seen in all layers gastrointestinal tract (As we know, the inflammation of ulcerative colitis (UC) is limited to the mucosa, while in Crohn’s disease (CD) the inflammation is transmural and can be seen in all layers of the gut). One of ordinary skill in the art would have taken this teaching and inferred that a method used to lower the DAI of mice with colitis would not work on a mouse with CD, due to CD causing inflammation in all layers of the bowel.
The level of one of ordinary skill needed to make/use the composition in the manner described in the claim is high. The artisan would need to know exactly what the composition described in the current invention would result in the treatment of all GI diseases without necessary support from the specification or the assistance of prior art.
Claims 1, 2, 4-10 and 12 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. 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 composition for oral administration for treatment of gastrointestinal disease or injury of a subject, said composition comprising: nanoemulsion particles (NEs) comprising a hydrophobic liquid core, and at least one hydrophobic surfactant (S1) and at least one hydrophilic surfactant (S2) in the external layer, said surfactants being nonionic polar surfactants surrounding the core; wherein the liquid core comprises one or more therapeutically active agent(s);and wherein the NEs are combined with a self-assembling peptide. The specification fails to disclose how the composition of claim 1 can be used to treat all GI diseases. Applicant shows that the composition can be used in the treatment of DSS-induced colitis (a model typically used to mimic human Inflammatory Bowel Disease). The ability for PS_NE_TFC to decrease in DAI score in DSS induced colitis in mice cannot be used as proof that PS_NE_TFC can be used to treat GI diseases, as colitis is not representative of all GI disease types. Colitis cannot model the specific characteristics found in the various different GI diseases the instant invention claims to treat. Ford teaches that while individuals with Irritable Bowel Syndrome (IBS) and IBD may present the same, or similar, symptoms (due to the GI tract being able to express only a limited amount of symptoms), the two have different hallmark indicators, for instance, mucosal inflammation and fecal calprotectin can be seen in IBD, while IBS is a functional disorder with no biomarker and Singh et al teaches that there is significant variation in the treatment of inflammatory bowel disease (IBD) provided by GI physicians, due to IBD encompassing a group of complex disorders, spanning from ulcerative colitis to Crohn’s disease, as taught above.
There are no other structures, drawings, or teachings of a composition being able to treat all GI diseases and injuries. The level of skill in the art is such that the ordinary skilled artisan would not be able to differentiate without further testing what portion of the instant invention is able to treat all GI disease from the portion of the current invention able to treat colitis induced in mice. The disclosures of the claimed composition as shown in the specification (treatment of DSS-induced colitis) are not representative of what is claimed (treatment of all GI diseases). Therefore, the specification fails to satisfy the written description requirement of 35 U.S.C. 112(a) or 35 U.S. C.112, first paragraph, with respect to claims 1, 2, 4-10 and 12.
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 8-10 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 8 is drawn to “The composition of claim 1, where the self-assembling peptide is any one of the peptides chosen from Table 1 (SEQ ID NOs: 1-24)”. The claim is indefinite because there is reference to a table included in the specification. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Claims 9-10, which depend from claim 8, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as these claims incorporate, by dependency, the indefiniteness of claim 8.
35 U.S.C. § 101
Examiner does not reject claims 1, 2, 4-10 and 12 under 35 U.S.C 101 due to the results of the following subject matter eligibility test using the generic claim, claim 1:
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Yes. The claim is to a composition for oral administration for treatment of gastrointestinal disease of injury of a subject.
Can analysis be streamlined?
Yes. When the claim is viewed as a whole, the eligibility of the claim is self-evident. The claim is directed to a composition used for treating and recites elements that amount to significantly more than the judicial exception.
Therefore, claims 1, 2, 4-10 and 12 of the instant application recite eligible subject matter under 35 U.S.C. 101 and are not subject to this rejection.
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, 4, 6-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yucel et al, hereafter “Yucel”, (US 2020/0246404 A1; in the IDS filed 14 January 2024), in view of Gil et al, hereafter “Gil”, (US 2020/0399310 A1).
Claim 1 is directed towards a composition for oral administration for treatment of gastrointestinal disease or injury of a subject, said composition comprising: nanoemulsion particles (NEs) comprising a hydrophobic liquid core, and at least one hydrophobic surfactant (S1) and at least one hydrophilic surfactant (S2) in the external layer, said surfactants being nonionic polar surfactants surrounding the core; wherein the liquid core comprises one or more therapeutically active agent(s); and wherein the NEs are combined with a self-assembling peptide.
Yucel teaches a composition for oral administration for the treatment of a gastrointestinal disease or injury in a patient ([0002] “The compositions of the present invention are suitable for oral administration.”; [0205] “The compositions of the present invention are preferably for oral administration.”; ([0322] “In one embodiment, the disease or disorder is selected from: … gastrointestinal disorders, inflammation or inflammatory condition, inflammatory bowel disease, Crohn's disease, irritable bowel syndrome…”).
Yucel also teaches the composition comprising nanoemulsion particles with a hydrophobic liquid core, and at least one hydrophobic surfactant and at least one hydrophilic surfactant in the external layer, with the surfactants being nonionic polar surfactants surrounding the core, wherein the core optionally has a therapeutically active agent ([0118] “Some of the compositions of the present invention form emulsions, preferably nanoemulsions…”; [0126] “In another embodiment, the composition comprises at least two surfactants, independently, with an HLB value selected from 9, 10, 11, 12, 13, 14, 15, 16, greater than 16, 9-17, 9-16.7, 9-16, 9-15, 9-14, 10-17, 10-16.7, 10-16, 10-15, 12-14, 12-16, 14-16, 14-17, 15-17, and between 10-14.”; [0207] “For example, relatively lipophilic surfactants are more soluble in fats, oils and waxes, and typically have HLB values less than or about 10, while relatively hydrophilic surfactants are more soluble in aqueous compositions, for example, water, and typically have HLB values greater than or about 10.”; [0209] “… the hydrophilic portions of the surfactant molecules contact the aqueous or the water phase, while the hydrophobic portions form the core of the micelle, which can encapsulate non-polar ingredient(s), for example, a cannabinoid.”). Yucel also teaches the nanoemulsions used for the treatment of gastrointestinal disorders being encapsulated in gels, but that the gels are subject to leakage at times, and that having the composition comprise a ratio of 1:1 polysorbate 80:TPGS stopped leakage ([0421] “Unsealed hard gelatin capsules containing formulations comprising a large amount of polysorbate 80 were found to be prone to leakage. … A formulation with a ratio of 1:1 polysorbate 80:TPGS, however, did not leak under the same conditions.”).
Yucel does not teach is the nanoemulsion particles being combined with self-assembling peptide.
Gil teaches self-assembling peptides forming into hydrogels at a near neutral pH ([0009] “In some embodiments, peptides included in provided compositions are self-assembling peptides.”; [0087] “In some embodiments, provided preparations are characterized by more stable hydrogel formation, and/or other attributes relative to a standard or reference preparation, as described herein.”; [0114] “In some embodiments, provided compositions are characterized by a pH at or above about 2.5-4.0; in some embodiments, provided compositions are characterized by a pH closer to physiological pH.”; [0149] “In some embodiments, physiological conditions (e.g., elevated pH and salt ionic strength) may accelerate gelation of peptide compositions.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Yucel’s composition used in the treatment of gastrointestinal disease or injury by combining it with the method of administering nanoemulsion particles taught by Gil. Yucel teaches the administering nanoemulsion particles in hard gelatin capsules ([0421] “Unsealed hard gelatin capsules containing formulations…”), while Gil teaches self-assembling peptides being able to form hydrogels. It would have been obvious to one of ordinary skill in the art to apply the self-assembling peptide formed hydrogels of Gil to the composition taught by Yucel due to Gil teaching the stability and accelerated gelation brought by the peptide formed hydrogel. This modification provides another effective way of administering the therapeutic agent of Yucel to target gastrointestinal tissue following oral administration, while minimizing leakage.
Claim 4 is directed towards the composition of claim 1, wherein the composition is administered in the form of capsule or tablet.
The teaching of Yucel and Gil are described and applied to claim 1 above.
With regard the limitation “wherein the composition is administered in the form of capsule or tablet”, Yucel teaches the composition being administered via capsule or tablet ([0267] “The unit dose (or serving) may be in the form of a syrup, drops, micellar dispersion, emulsion, solution, suspension, tablet, bolus, troche, tincture, oral/buccal/sublingual spray, lozenge, dissolving strip, or capsule.”).
Claim 6 is directed towards the composition of claim 1, wherein the surfactant comprises S1 being Polyoxyethylene(40) stearate (Myrj®52) and S2 being oleoyl polyoxyl-6 glycerides (Labrafil®M1944CS).
The teaching of Yucel and Gil are described and applied to claim 1 above.
With regard the limitation “wherein the surfactant comprises S1 being Polyoxyethylene(40) stearate (Myrj®52) and S2 being oleoyl polyoxyl-6 glycerides (Labrafil®M1944CS)”, Yucel teaches a composition used to treat gastrointestinal disease where the surfactants can be selected from a list, including Polyoxyethylene(40) stearate (PEG 40 Stearate) and oleoyl polyoxyl-6 glycerides ( ([0127] “In some embodiments, the surfactant is selected from: … PEG 300 oleic glycerides (Labrafil M 1944), … PEG 40 stearate, or a combination thereof.”).
Claim 7 is directed towards the composition of claim 1, wherein the ratio of S1 to S2 is between 1 and 5 wt./wt.
The teaching of Yucel and Gil are described and applied to claim 1 above.
With regard the limitation “wherein the ratio of S1 to S2 is between 1 and 5 wt./wt.”, Yucel teaches the surfactant in the composition ([0175] “wherein the wt. % of active ingredient, MCT and/or LCT, first surfactant, and second surfactant (where the first and second surfactant are different) is selected from one of the compositions in Table 1 below”). The chart on pages 15-16 show surfactant 1 and 2 having multiple ratios, including a 1:1 ratio.
Claim 8 is directed towards the composition of claim 1, where the self-assembling peptide is any one of the peptides chosen from Table 1 (SEQ ID NOs: 1-24).
In a response filed on 12/03/2025, Applicants elected SEQ ID NO: 1 as the self-assembling peptide.
The teaching of Yucel and Gil are described and applied to claim 1 above.
With regard to the limitation “where the self-assembling peptide is SEQ ID NO: 1”, Gil teaches a peptide with 100% identity to the instant SEQ ID NO: 1 ([0009] “In some embodiments, peptides included in provided compositions are self-assembling peptides. … In some embodiments, peptides included in provided compositions have an amino acid sequence that includes one or more repeats of Arg-Ala-Asp-Ala (RADA). … In some embodiments, the peptides may be IEIK13, KLD12, or RADA16.”)
It would have been obvious to one of ordinary skill in the art before the effective filing date to combine the teachings of Yucel and Gil to arrive at the presently claimed invention, as stated above. Gil teaches self-assembling peptides being able to form hydrogels, and specifically includes the a peptide with 100% identity to the instant SEQ ID NO: 1. It would have been obvious to one of ordinary skill in the art to apply the self-assembling peptide formed hydrogels of Gil to the composition taught by Yucel due to Gil teaching the stability and accelerated gelation brought by the peptide.
Claim 9 is directed towards the composition of claim 8, wherein the self-assembling peptide is provided in a dry form.
The teaching of Yucel and Gil are described and applied to claim 8 above.
Gil teaches the composition as described above, where the peptide compositions are in the form of a dry powder ([0154] “In some embodiments, peptide compositions in accordance with the present invention are in the form of a dry powder, a solution, a gel (e.g., a hydrogel), or any combination thereof.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date to combine the teachings of Yucel and Gil to arrive at the presently claimed invention, as stated above. Gil discloses the peptide described in the instant SEQ ID NO: 1, as being able to be in the form of a powder, a solution, or a gel. It would haven obvious to the artisan that the self-assembling peptide could be in the form of a dry powder due to the disclosure of Gil showing it as a known embodiment.
Claim 10 is directed towards the composition of claim 8, wherein the self-assembling peptide is RADA16 (SEQ ID NO:1).
The teaching of Yucel and Gil are described and applied to claim 8 above.
With regard to the limitation “where the self-assembling peptide is SEQ ID NO: 1”, Gil teaches a peptide with 100% identity to the instant SEQ ID NO: 1 ([0009] “In some embodiments, peptides included in provided compositions are self-assembling peptides. … In some embodiments, peptides included in provided compositions have an amino acid sequence that includes one or more repeats of Arg-Ala-Asp-Ala (RADA). … In some embodiments, the peptides may be IEIK13, KLD12, or RADA16.”)
It would have been obvious to one of ordinary skill in the art before the effective filing date to combine the teachings of Yucel and Gil to arrive at the presently claimed invention, as stated above. Gil teaches self-assembling peptides being able to form hydrogels, and specifically includes the a peptide with 100% identity to the instant SEQ ID NO: 1. It would have been obvious to one of ordinary skill in the art to apply the self-assembling peptide of Gil to the composition taught by Yucel due to Gil teaching the stability and accelerated gelation brought by the peptide.
Therefore, the claimed invention would have been prima facie obvious to the artisan of ordinary skill at the time before the effective filing date of the claimed invention.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yucel et al, hereafter “Yucel”, (US 2020/0246404 A1; in the IDS filed 14 January 2024), in view of Gil et al, hereafter “Gil”, (US 2020/0399310 A1), as applied to claim 1 above, and further in view of Laroui et al, hereafter “Laroui”, (Drug-Loaded Nanoparticles Targeted to the Colon With Polysaccharide Hydrogel Reduce Colitis in a Mouse Model, Gastroenterology, Volume 138, Issue 3, 2010, Pages 843-853.e2, ISSN 0016-5085, https://doi.org/10.1053/j.gastro.2009.11.003.).
Claim 2 is directed towards the composition of claim 1, wherein the self-assembling peptide, combined with NEs, is in a dry form, and which when being hydrated at a slightly acidic or near-neutral pH assembles into a hydrogel matrix enveloping the NEs, thereby adhering to and/or delivering the active agent to the intestinal walls upon oral administration to the subject.
The teaching of Yucel and Gil are described and applied to claim 1 above.
Gil teaches the composition as described above, where compositions comprising a self-assembling peptide are in the form of a dry powder ([0154] “In some embodiments, peptide compositions in accordance with the present invention are in the form of a dry powder, a solution, a gel (e.g., a hydrogel), or any combination thereof.”).
What Yucel and Gil do not teach is the combined self-assembling peptide and nanoemulsions being hydrated at slightly acidic or near-neutral and adhering and/or delivering the active agent to the intestinal walls.
Laroui teaches the administration of peptide loaded nanoparticles to solutions mimicking the pH of colonic fluid (pH 5 and 6) (page 849; Swelling Degree of the Biomaterial Into the Digestive Tract - “Together, these results indicate that this [biomaterial made out of polysaccharides] could be used to deliver KPV-loaded NPs to intestinal solutions of pH 5 and 6 (the approximate pH of the colonic fluid) but not at acidic pH values of 1, 2, or 3 (the approximate pH of the gastric fluid).”
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Yucel and Gil as applied to claim 1. Yucel teaches administering nanoemulsion particles in hard gelatin capsules ([0421] “Unsealed hard gelatin capsules containing formulations…”), while Gil teaches self-assembling peptides being able to form hydrogels. Gil teaches the combination of a self-assembling peptide and a nanoemulsion in a dry form. Laroui discloses that there is a way to administer a hydrogel so that it swells in an environment with a near neutral pH, resulting in the nanoparticles being delivered into the colon. It would have been obvious to one of ordinary skill in the art to apply the teachings of Yucel and Gil to the administration method taught in Laroui. One would have had a reasonable expectation of success because the established method of administering peptides that mediates delivery of medicaments to the colon based on pH was used in the art prior to the effective filing date of the current invention. (See MPEP 2143 (I)(D)).
Claim(s) 5 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yucel et al, hereafter Yucel, (US 2020/0246404 A1; in the IDS filed 14 January 2024), in view of Gil et al, hereafter Gil, (US 2020/0399310 A1), as applied to claim 1 and 4 above, and further in view of Hudson et al, hereafter Hudson, (US 2019/0389895 A1; in the IDS filed 14 January 2024).
Claim 5 is directed towards the composition of claim 4, wherein the capsule or the tablet slowly dissolves in the stomach of the subject or in post-stomach intestine, thereby forming a depot in the gastrointestinal tract of the subject, thereby releasing the composition into the intestine of the subject.
The teachings of Yucel and Gil are described and applied to claim 4 above.
Yucel and Gil do not teach the capsule or tablet, described in claim 4, slowly dissolving in the stomach of the subject or in post-stomach intestine, thereby forming a depot in the gastrointestinal tract of the subject, thereby releasing the composition into the intestine of the subject.
With regard the limitation described in claim 5, Hudson teaches that the composition can be formulated for slow release within the intestinal tract of the subject ([0109] “Pharmaceutical compositions of the invention may also be formulated to provide slow or controlled release of the active agent using … may be formulated so that they release the active ingredient only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Yucel and Gil with the slow releasing properties of the invention described in Hudson. Yucel teaches the use of a composition to treat gastrointestinal disease, as does the specification of Hudson ([0002] “The invention is directed to compounds designed for targeted delivery of a JAK inhibitor to the gastrointestinal tract. The invention is also directed to pharmaceutical compositions comprising such compounds, methods of using such compounds to treat gastrointestinal inflammatory diseases”). It would have been obvious to apply the gastrointestinal slow-release formulation taught by Hudson to the composition made obvious by Yucel and Gil in order to deliver a therapeutic to a targeted region of the gastrointestinal tract and to control the release of the therapeutic to treat a gastrointestinal disease for an extended period of time.
Claim 12 is directed towards the composition of claim 1, wherein the active agent is chosen from the group consisting of Tofacitinib, Curcumin, and Budesonide.
In a response filed on 12/03/2025, Applicants elected Tofacitinib as the active agent.
The teaching of Yucel and Gil are described and applied to claim 1 above.
Yucel and Gil do not teach the active agent described in claim 1 being Tofacitinib.
With regard to the limitation “wherein the active agent is Tofacitinib”, Hudson teaches the use of Tofacitinib in treating gastrointestinal disorders ([0138] “Accordingly, the glucuronide prodrugs of tofacitinib of the invention are expected to be useful for the treatment of inflammatory bowel disease, in particular ulcerative colitis.”)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Yucel and Gil with the use of Tofacitinib in the treatment of gastrointestinal diseases, as described in Hudson. Yucel teaches the use of a composition to treat gastrointestinal disease, as does the specification of Hudson ([0002] “The invention is directed to compounds designed for targeted delivery of a JAK inhibitor to the gastrointestinal tract. The invention is also directed to pharmaceutical compositions comprising such compounds, methods of using such compounds to treat gastrointestinal inflammatory diseases”). It would have been obvious to apply Tofacitinib as taught by Hudson as the active ingredient in the composition made obvious by Yucel and Gil in order to deliver Tofacitinib to the gastrointestinal tract in order to treat gastrointestinal disease.
Summary
Claims 1, 2, 4-10 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ). Claim(s) 1, 2, 4-10 and 12 are rejected under 35 U.S.C. 103.
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Daliyah M. Brown whose telephone number is (571)272-0136. The examiner can normally be reached Monday-Thursday 9:00 am - 4:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Daliyah M. Brown/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654