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 Claims
Claims 1-18 were originally filed on August 19, 2021.
The amendment received on January 30th 2024, cancelled claims 2-4; amended claims 1, 5, 9, 11, 17 and 18.
The amendment received on May 13th 2024, cancelled claims 1 and 5-18 and added claims 19-38.
The amendment received on January 16th 2025, amended claims 21, 27, 31 and 37.
The amendment received on December 10th 2025, amended claims 25 and 35; and added new claim 39.
Claims 19-39 are currently pending and under consideration.
Priority
The present application claims the benefit under 35 U.S.C. 119 (e) to U.S. Provisional Application No. 63/068,131 filed August 20, 2020. Applicant’s 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.
Response to Arguments
1. Applicant’s arguments, see Remarks, filed 12/10/2025, with respect to the claim objections have been fully considered and are persuasive. The objection to claims 25 and 35 has been withdrawn.
2. Applicant’s arguments, see Remarks, filed 12/10/2025, with respect to 35 U.S.C. 103 have been fully considered but are not persuasive. The 35 U.S.C. 103 rejection of claims 19-38 has been maintained.
Maintained/Modified Rejections Necessitated by Amendments
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 non-obviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 19-39 are rejected under 35 U.S.C. 103 as being unpatentable over Suzuki et al. WO2017002786A1 published on January 5, 2017 (hereinafter “Suzuki”) (note: reference is made to the English language machine translation), in view of McDowell et al., “Inflammatory Bowel Disease,” Natl. Library Med., available at https://www.ncbi.nlm.nih.gov/books/NBK470312/, 12 pages (first available 2020) (hereinafter “McDowell”), Soares et al., Pharma Nutrition, 6 (2018) 119-124 (hereinafter “Soares”), Olmstead et al. US 2020/0017509A1 published on January 16, 2020 (hereinafter “Olmstead), and Feuerstein et al., Gastroenterology (2020), vol. 158, issue 5, pp. 1450-1461 (hereinafter “Feuerstein”). NOTE: the rejection has been updated in light of Applicant’s amendments to the claims; namely, addition of new claim 39.
Regarding claims 19 and 29, Suzuki teaches a composition for promoting GLP-2 secretion comprising a cyclic dipeptide having an amino acid as a constitutional unit or a salt thereof as an active ingredient, wherein the cyclic dipeptide or a salt thereof is cyclohistidyl proline [Cyclo (His-Pro)] (see Suzuki, Machine Translation, pgs. 1, paragraph 9 to pg. 2, paragraph 1). Suzuki also teaches that the composition for accelerating secretion of GLP-2 has an intestinal inflammation inhibitory action; that is not only effective for suppressing inflammation of the bowel but also maintaining homeostasis of intestinal function (see Suzuki, Machine Translation, claim 6 and pg. 2 and pg.11 paragraph 2). Thus, Suzuki’s teachings are suggestive of administering cyclo(His-Pro) to suppress bowel inflammation.
Suzuki adds that the cyclic dipeptide or its salt, the composition for promoting secretion of GLP-2, may contain optional additives and optional ingredients usually used depending on its form (see Suzuki, Machine translation, pg. 9, paragraph 4). Examples of these additives and/or ingredients include physiologically active ingredients such as vitamins (vitamin E and vitamin C), minerals, nutritional ingredients and perfumes, excipients to be incorporated in the formulation, binders, an emulsifier, a tonicity agent (isotonizing agent), a buffer, a dissolution aid, an antiseptic, a stabilizer, an antioxidant, a colorant, a coagulant, a coating agent (see Suzuki, Machine translation, pg. 9, paragraph 4). Thus, the teachings of Suzuki satisfy the claim limitations as recited in instant claims 19 and 29, where the composition consists of an active ingredient (i.e., cyclo(His-Pro) or a pharmaceutically acceptable salt thereof) and a carrier or an excipient.
Although the composition of Suzuki incorporates excipients such as minerals, Suzuki does not expressly teach that the mineral is zinc.
Soares teaches that Zinc supplementation is indicated as an adjunctive therapy for the treatment of chronic and inflammatory diseases (See Soares, pg. 120, left column). Thus, the teachings of Soares are suggestive of adding zinc gluconate as the mineral to the pharmaceutical composition taught by Suzuki as recited in instant claims 19 and 29.
Suzuki does not expressly teach that the promotion of GLP-2 reverses, alleviates, and/or inhibits progress of IBD in a subject in need thereof, where IBD is ulcerative colitis (UC) as recited in instant claims 19 and 29.
McDowell teaches that Inflammatory bowel disease (IBD) is characterized by repetitive episodes of inflammation of the gastrointestinal tract caused by an abnormal immune response to gut microflora (see McDowell, Introduction, pg. 1, 2nd paragraph). McDowell also teaches that inflammatory bowel disease encompasses two types of idiopathic intestinal disease that are differentiated by their location and depth of involvement in the bowel wall; namely, ulcerative colitis and Chron’s disease (see McDowell, Introduction, pg. 1, 2nd paragraph). Ulcerative colitis (UC) involves diffuse inflammation of the colonic mucosa (see McDowell, Introduction pg. 1, 2nd paragraph). Most often, UC affects the rectum (proctitis), but it may extend into the sigmoid (proctosigmoiditis), beyond the sigmoid (distal ulcerative colitis), or include the entire colon up to the cecum (pancolitis) (see McDowell, Introduction pg. 1, 2nd paragraph); thereby constituting where UC involves inflammation in a component of the bowel. Thus, McDowell provides a correlation between bowel inflammation and IBD and UC thereby suggesting that suppressing bowel inflammation would treat IBD and UC.
Suzuki does not teach that the subject is non-responsive to treatments by topical corticosteroid, 5-aminosalicilic acid (5-ASA), and/or antibiotics as recited in instant claims 19 and 29.
Feuerstein et al., teach official recommendations of the American Gastroenterological Association (AGA) on the management of moderate to severe ulcerative colitis (UC) (see Feuerstein et al., pg. 1450, left column, paragraph 1). Feuerstein’s Table 4 displays recommendations for the management of moderate to severe ulcerative colitis (see Feuerstein, pg. 1453, Table 4). It is noted that the recommendations are directed to different scenarios based on severity of the condition and treatment plan; Table 4 displays 11 recommendations and two of those suggest using other treatments such as use of biologic agents with or without immunomodulator therapy after failure of 5-ASA (see Feuerstein, pg. 1453, Table 4, entry #6), and for patients who have achieved remission with biologic agents and/or immunomodulators or tofacitinib, the AGA suggest against continuing 5-ASA for induction and maintenance of remission (see Feuerstein, pg. 1453, Table 4, entry #7). As such, the teachings of Feuerstein are suggestive of the claim limitations as recited in instant claims 19 and 29 where the subject is non-responsive to treatments by 5-aminosalicilic acid (5-ASA). Thus, an ordinary skilled artisan would be motivated with a reasonable expectation of success to administer a composition consisting of cyclo(His-Pro) as taught by Suzuki to a patient who is non-responsive to 5-ASA in order to suppress bowel inflammation, which is characteristic of IBD and UC as taught by McDowell, in light of the teachings of Feuerstein as further articulated below.
From the teaching of the references, the Examiner recognizes that it would have been prima
facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Suzuki and administer an effective amount of a composition consisting of cyclo(His-Pro) to a subject in order to reverse, alleviate and/or inhibit progression of UC as a form of IBD by suppressing bowel inflammation. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because IBD was known to be characterized as a chronic inflammatory disease characterized by repetitive episodes of inflammation of the gastrointestinal tract, and because UC was known to be a species of IBD as taught by McDowell. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that a composition consisting of an effective amount of cyclo(His-Pro) of Suzuki was administered to a subject in order to suppress bowel inflammation. Therefore, administering the composition to a subject suffering from UC as a species of IBD would support the reversion, alleviation and/or inhibition of the progression of UC by suppressing bowel inflammation by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Additionally, it would have been prima facie obvious to one with ordinary skill in the art at the time the invention was filed to combine the teachings of Feuerstein with those of Suzuki and McDowell. The person of ordinary skill in the art would have found it obvious to come up with an alternative method of reversing, alleviating and/or inhibiting progression of UC by suppressing bowel inflammation in patients non responsive to classic anti-inflammatory drugs; since it was known in the art that 5-Aminosalicylates (5-ASA) are not effective nor suitable in treating inflammation nor maintaining remission of UC in a subset of subjects and this subset of subjects was known to be treated with a biologic agent as taught by Feuerstein. A person of ordinary skill in the art would have had found it obvious with a reasonable expectation of success given that a composition consisting of an effective amount of cyclo(His-Pro) of Suzuki was administered to a subject in order to suppress bowel inflammation. Therefore, administering the composition as a biologic agent to a subject suffering from UC and who is non-responsive to 5-ASA would support the reversion, alleviation and/or inhibition of the progression of UC by suppressing bowel inflammation by constituting some teaching, suggestion or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Regarding claims 20-22 and 30-32, Suzuki does not teach wherein the cyclo(His-Pro) is the claimed cyclo(His-Pro) hydrate, e.g. crystalline cyclo(His-Pro) hydrate having the claimed characteristics recited in instant claims 20-22 and 30-32.
Olmstead teaches that anhydrous cyclo(His-Pro) is the form that has been known in prior art and has potential therapeutic applications, however cyclo(His-Pro) hydrate has superior stability over other forms of cyclo(His-Pro) (see Olmstead, pg.1, para[0004] and [0006]). The disclosure of Olmsted teaches cyclo(His-Pro)hydrate crystalline form (“CHP Hydrate” or “Pattern 2” compound) that may be characterized and distinguished from other solid forms of CHP using various analytical techniques including but not limited to XRPD (see Olmsted, pg. 1, para[0005]). CHP hydrate has superior stability over amorphous cyclo(His-Pro) (Pattern 1”) (see Olmsted, pg. 1, para[0006]). Based on this surprising discovery, Pattern 2 can be used alone as a single component drug rather than using Pattern 1 or a mixture of Pattern 1 and Pattern 2 (see Olmsted, pg. 1, para[0006]). Olmstead discloses several embodiments such as a process for the isolation of Pattern 2 by crystallization using solvents (see Olmstead, pg. 1, para[0007]). In another embodiment, Pattern 2 is stable at typical room temperature storage conditions for about 6 months, or about 12 months, or about 18 months, or about 24 months, or about 36 months (see Olmstead, pg. 1, para[0008]). In yet another embodiment, the present disclosure is directed to substantially pure Pattern 2 material, where the Pattern 2 material is at least about 90% pure, or at least about 95%, 96%, 97%, 98%, 99%, or 100% pure (see Olmstead, pg. 1, para[0009]). Furthermore, the XRPD patterns taught by Olmstead include peaks at about 13.7 degrees 2θ, 17 degrees 2θ and about 27.3 degrees 2θ, further including a more characteristic peak at about 10 degrees 2θ, with all peak assignments including variations of plus or minus 0.2 degrees 2θ (see Olmstead, pg. 1 para[0010-0012] and pg. 5, para[0152-0154]). The X-ray powder diffraction (XRPD) peaks taught by Olmstead confirm the physical characteristics of the cyclo(His-Pro) hydrate and coincide with those of instant claims 20-22 and 30-32.
Additionally and/or alternatively, even if Olmstead did not expressly use X-ray diffraction to characterize cyclo(His-Pro) at specific peaks, since Olmstead teaches cyclo(His-Pro) hydrate thereby constituting a well-known product, the functional property (i.e., exhibiting peaks at 2θ values of 10° +/- 0.2°, 13.7° +/- 0.2°, 17 +/- 0.2° and 27.3 +/- 0.2° by using an XRPD) of the product as claimed and the known product would necessarily read upon the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new functional property (i.e., exhibiting peaks at 2θ values of 10° +/- 0.2°, 13.7° +/- 0.2°, 17 +/- 0.2° and 27.3 +/- 0.2° by using an XRPD) which would necessarily read upon the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977).
From the teaching of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Suzuki and incorporate the teachings of Olmsted to produce a more stable composition consisting of cyclo(His-Pro)hydrate crystalline form (“CHP Hydrate” or “Pattern 2” compound). One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because cyclo(His-Pro)hydrate crystalline form was known to have superior stability over other forms of cyclo(His-Pro), and because the cyclo(His-Pro)hydrate in crystalline form is stable at typical room temperature, can be stored up to 36 months and it can reach a purity of about 90% or at least about 95%, 96%, 97%, 98%, 99%, or 100% as taught by Olmsted. One of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success given that a composition comprising an effective amount of cyclo(His-Pro) of Suzuki was administered to a subject in order to suppress bowel inflammation. Therefore, utilizing the cyclo(His-Pro)hydrate in crystalline form as the cyclo(His-Pro) form would support the improved physical and chemical stability of the composition comprising cyclo(His-Pro) by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Regarding claims 23, 28, 33 and 38, As previously mentioned, Suzuki teaches a pharmaceutical composition comprising cyclo(His-Pro) and other excipients such as vitamins, minerals, nutritional ingredients, perfumes, binders, emulsifiers, a tonicity agent (isotonizing agent), a buffer, a dissolution aid, an antiseptic, a stabilizer, an antioxidant, a colorant, a coagulant, a coating agent (see Suzuki, Machine Translation, pg. 9, paragraph 4). However, Suzuki does not expressly teach that the mineral is zinc or the amount of mineral included in the composition as recited in instant claims 23, 28, 33, and 38.
Soares teaches that zinc supplementation is indicated as an adjunctive therapy for the treatment of chronic and inflammatory diseases (See Soares, pg. 120, left column), more specifically zinc can be beneficial to the treatment of ulcerative colitis, where 35 mg of zinc gluconate per day was administered to patients diagnosed with ulcerative colitis (thereby constituting the claim limitations recited in instant claims 23 and 33. As such, Soares teaches a specific amount of zinc in the form of zinc gluconate where this specific amount lies within one of the ranges claimed in instant claims 28 and 38, i.e., 10-50 mg/day.
Additionally and/or alternatively, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.). Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed amount of zinc administered to the subject in a range of about 10-50 mg/day would have been obvious to one of ordinary skill in the art since the prior art amount (i.e., 35 mg of zinc gluconate per day) lies within the claimed amount range (i.e., of about 0.1-1 mg/day, about 1-10 mg/day, 10-50 mg/day, 50-100 mg/day, 100-150 mg/day, 150-200 mg/day, 200-300 mg/day, 300-400 mg/day, 400-500 mg/day, 500-600 mg/day, 600-700 mg/day, 700-800 mg/day, 800-900 mg/day, 900-1000 mg/day, 1000- 1100 mg/day, 1100-1200 mg/day, 1200-1300 mg/day, 1300-1400 mg/day, 1400-1500 mg/day, 1500-1600 mg/day, 1600-1700 mg/day, 1700-1800 mg/day, 1800-1900 mg/day, or 1900-2000 mg/day, as calculated in terms of zinc cation). Similarly, the claimed effective amount of the second composition consisting of zinc would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 35 mg of zinc gluconate per day) lies within the claimed effective amount of the second composition (i.e., of about 0.1-1 mg/day, about 1-10 mg/day, 10-50 mg/day, 50-100 mg/day, 100-150 mg/day, 150-200 mg/day, 200-300 mg/day, 300-400 mg/day, 400-500 mg/day, 500-600 mg/day, 600-700 mg/day, 700-800 mg/day, 800-900 mg/day, 900-1000 mg/day, 1000- 1100 mg/day, 1100-1200 mg/day, 1200-1300 mg/day, 1300-1400 mg/day, 1400-1500 mg/day, 1500-1600 mg/day, 1600-1700 mg/day, 1700-1800 mg/day, 1800-1900 mg/day, or 1900-2000 mg/day, as calculated in terms of zinc cation). Thus, the teachings of Soares are suggestive of the claim limitations as recited in instant claims 23, 28, 33, and 38 where zinc gluconate is administered to a subject in an effective amount ranging from about 10-50mg/day.
It would have been prima facie obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Suzuki and administer an effective amount of a composition comprising cyclo(His-Pro) to a subject in combination with zinc gluconate as a mineral in order reverse, alleviate and/or inhibit progression of UC as a form of IBD by suppressing bowel inflammation. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because an effective amount of zinc gluconate was known to be used as an adjunctive therapy to treat UC in patients as taught by Soares. One of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success given that a composition comprising an effective amount of cyclo(His-Pro) and a mineral of Suzuki was administered to a subject in order to suppress bowel inflammation. Therefore, administering an effective amount of zinc gluconate in combination with the composition of Suzuki such that the zinc gluconate is substituted as the mineral would support a method for reversing, alleviating, and/or inhibiting progress of UC by suppressing bowel inflammation by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Additionally and/or alternatively, "it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose… [T]he idea of combining them flows logically from their having been individually taught in the prior art." (MPEP 2144.06). In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from their having been individually taught in prior art. Therefore, since the combination of Suzuki, McDowell, and Feuerstein demonstrate cyclo(His-Pro) as part of a method for reversing, alleviating and/or inhibiting progress of UC as a form of IBD by suppressing bowel inflammation when administered to a subject who is non-responsive to 5-ASA, and Soares demonstrates that zinc gluconate treats UC, it would have been obvious to combine the two agents with the expectation that such a combination would be effective in reversing, alleviating and/or inhibiting progress of UC as a form of IBD by suppressing bowel inflammation. Thus, combining the compositions of Suzuki, McDowell, Feuerstein, and Soares flows logically from their having been individually taught in prior art.
Regarding claims 24-25 and 34-35, Suzuki teaches that in addition to providing a composition having a highly effective GLP-2 secretion promoting action, by ingesting the GLP-2 secretion promoting composition, it is possible to obtain an intestinal protective effect, intestinal inflammation suppressing effect, intestinal mucosa proliferating effect, maintenance effect of the intestinal mucosal barrier function, and a digestive and absorption promoting effect (see Suzuki, Machine translation, pg. 3, paragraph 2). Suzuki’s invention can provide a new means of contributing to intestinal protection, inhibition of intestinal inflammation, proliferation of intestinal mucosa, maintenance of barrier function of intestinal mucosa, promotion of digestive absorption and intestinal movement (see Suzuki, Machine translation, pg. 3, paragraph 2).
Additionally, even though Suzuki did not expressly teach the administration of the composition improves stool consistency, decreases blood occult, and/or ameliorates bodyweight loss or that administration of the composition results in one or more of the following: (a) inhibition of colon length reduction, (b) repair of intestinal leakage, (c) inhibition of intestinal leakage, (d) reduce or inhibit lymphocytes infiltration into colon tissue, (e) suppress epithelial erosion, and (f) inhibition of reduction of colon wall submucosa thickness; since Suzuki teaches ingesting a GLP-2 secretion promoting composition thereby constituting the claimed manipulative step of administering a composition consisting of cyclo (His-Pro) as an active ingredient, the functional properties (i.e., improvement of stool consistency, decrease in blood occult, and/or amelioration of bodyweight loss, as well as: (a) inhibition of colon length reduction, (b) repair of intestinal leakage, (c) inhibition of intestinal leakage, (d) reduction or inhibition of lymphocytes infiltration into colon tissue, (e) suppression of epithelial erosion, and (f) inhibition of reduction of colon wall submucosa thickness) that result from the manipulative step of administering the composition consisting of cyclo(His-Pro) as an active ingredient as claimed and the known GLP-2 secretion promoting composition would necessarily read upon the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of new functional properties (i.e., improvement of stool consistency, decrease in blood occult, and/or amelioration of bodyweight loss, as well as: (a) inhibition of colon length reduction, (b) repair of intestinal leakage, (c) inhibition of intestinal leakage, (d) reduction or inhibition of lymphocytes infiltration into colon tissue, (e) suppression of epithelial erosion, and (f) inhibition of reduction of colon wall submucosa thickness) which would necessarily read upon the prior art do not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Therefore, the teachings of Suzuki satisfy the claim limitations as recited in instant claims 24-25 and 34-35 since the effects of Suzuki’s composition results in proliferation of intestinal mucosa, intestinal protection, inhibition of intestinal inflammation, maintenance of the intestinal mucosal barrier function, and promotion of digestion and absorption.
Regarding claims 26-27, 36-37 and 39; Suzuki teaches that the amount of the GLP-2 secretion promoting composition is appropriately set depending on the form, administration method, purpose of use, age, body weight and symptom of the patient or the subject to be administered to, and it is not constant (see Suzuki, Machine Translation, pg. 10, paragraph 5). The effective human intake of the composition is not constant but is preferably 10mg or more, more preferably 100mg or more per day (see Suzuki, pg. 10 para[52], machine translation), and when administered to bigger subjects Suzuki suggests an amount of 10mg/kg/day or more, more preferably 100 mg/kg/day or more of the total amount of the cyclic dipeptide or salt thereof (see Suzuki, pg. 10 para[53] machine translation). As such, Suzuki teaches effective amount ranges of cyclo(His-Pro), which overlap with the ranges claimed in instant claims 26-27 and 36-37 (i.e., 10-100mg/day and 10-2000mg/kg/day) to suppress bowel inflammation and thereby constitutes an effective amount of cyclo(His-Pro) as recited in instant claim 19.
Additionally, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.). Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). In the instant case, the claimed effective amount of a composition consisting of an active ingredient and a pharmaceutically acceptable carrier would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 10mg/kg/day or more, more preferably 100 mg/kg/day or more) lies within the claimed effective amount range (i.e., about 1-10 mg/day, […], or 2900-3000 mg/day and of about 0.001-0.005 mg/kg/day, […], or 1900-2000 mg/kg/day). Similarly, the claimed effective amount of the first composition would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 10mg/kg/day or more, more preferably 100 mg/kg/day or more) lies within the claimed effective amount of the first composition range (i.e., of about 1-10 mg/day, […], or 2900-3000 mg/day and 0.001-0.005 mg/kg/day, […], or 2900-3000 mg/kg/day).
With respect to the effective amount of the zinc as recited in claim 27 and the effective amount of the second composition as calculated in terms of zinc cation as recited in instant claim 37:
As previously discussed, Soares teaches that zinc supplementation is indicated as an adjunctive therapy for the treatment of chronic and inflammatory diseases, more specifically zinc can be beneficial to the treatment of ulcerative colitis, where 35 mg of zinc gluconate per day (see Soares, Abstract and pg. 120, left column). Thus, Soares teaches a specific amount of zinc in the form of zinc gluconate where this specific amount lies within one of the ranges claimed in instant claims 27 and 37. Therefore, an ordinary skilled artisan would be motivated with a reasonable expectation of success to combine the teachings of Suzuki, McDowell and Soares and administer an effective amount of a composition consisting of an active ingredient such as cyclo(His-Pro) to a subject in order to reverse, alleviate and/or inhibit progress of IBD.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 USC 103. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references above.
Applicant’s Arguments
Applicant contends that the webpage from where the McDowell reference (i.e., https://www.ncbi.nlm.nih.gov/books/NBK470312/) was retrieved shows the 2023 update date on its face, but does not contain its first publication date information, and that detailed information of the first publication date of McDowell was not provided (see Remarks, filed on 12/10/2025, pg. 11, footnote).
Applicant also asserts nowhere in Feuerstein or Suzuki is a suggestion to replace the biologics or immunomodulators mentioned in Feuerstein with a GLP-2 secretion-promoting composition of Suzuki and that combining Feuerstein with Suzuki requires hindsight, as Feuerstein addresses biologics and immunomodulators, not a GLP-2 secretion-promoting compound (see Remarks, filed 12/10/2025, pg. 13, second to last paragraph). Additionally that Suzuki and Feuerstein, individually or in combination do not provide a reasonable expectation of success to arrive at the claimed method either (see Remarks, filed 12/10/2025, pg. 13, second to last paragraph).
Response to Arguments
Applicant’s arguments filed on 12/10/2025 with respect to the 35 U.S.C 103 have been fully considered, but are not persuasive for the following reasons.
Regarding Applicant’s first argument with respect to the first publication date of the McDowell reference, it is acknowledged that the reference does not expressly indicate its first available publication date. However, based on the results obtained from https://web.archive.org/, an internet archive used by the USPTO to identify citable information of digital content such as dates, McDowell et al., “Inflammatory Bowel Disease,” Natl. Library Med., retrieved from https://www.ncbi.nlm.nih.gov/books/NBK470312/, was saved 22 times between July 23rd 2020 and May 30th, 2024 (see accompanying Internet Archive Results, McDowell, pg. 1). In other words, the McDowell reference was made available to the public via the world wide web on or before July 23rd 2020, which is prior to the filing date of Provisional Application 63/068,131 filed August 20th 2020. Therefore, it is evident that the first available publication date of the McDowell reference is prior to the effective filing date of the instant application (i.e., August 20th 2020). Thus, the reference qualifies as prior art.
In response to Applicant’s second arguments, i.e., nowhere in Feuerstein or Suzuki is a suggestion to replace the biologics or immunomodulators mentioned in Feuerstein with a GLP-2 secretion-promoting composition of Suzuki and that combining Feuerstein with Suzuki requires hindsight, as Feuerstein addresses biologics and immunomodulators, not a GLP-2 secretion-promoting compound, has been considered but it is not persuasive.
As evidenced by the 35 U.S.C 103 rejection above, there is not a single reference that teaches and/or suggests every claim limitation recited in instant claims 19 and 29 and the dependent claims. Additionally, Applicants are respectfully reminded that the 35 U.S.C 103 rejections is based on obviousness and pursuant to MPEP 2142, 35 U.S.C 103 authorizes a rejection where; to meet the claim, it is necessary to modify a single reference or to combine it with one or more other references (emphasis added). In other words, since the rejection is based on obviousness, it is unnecessary for every claim limitation to be taught and/or suggested by a single reference. Additionally, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In the instant case, an ordinary skilled artisan after reading the teachings of Feuerstein or Suzuki would have been motivated to arrive at the claimed invention. It is acknowledged that Feuerstein and Suzuki do not suggest a particular substitution of one element for another; however the cited art does teach biologics as an alternative treatment in the management of UC after failure of 5-ASA. Therefore, an ordinary skilled artisan would have been motivated to treat the condition with other alternative treatments, other than biologics. Since McDowell provides a correlation between bowel inflammation, inflammatory bowel disease and ulcerative colitis thereby suggesting that suppression of bowel inflammation would treat inflammatory bowel disease and ulcerative colitis.
An ordinary skilled artisan would have been motivated to read about other nontraditional alternatives to reduce bowel inflammation. Thus, an ordinary skilled artisan, after reading the teachings of Suzuki would have been motivated to accelerate secretion of GLP-2 with a composition comprising a cyclic dipeptide wherein the cyclic dipeptide or a salt thereof is cyclohistidyl proline (i.e., Cyclo(His-Pro)), because GLP-2 secretion has an intestinal inflammation inhibitory action that is not only effective for suppressing inflammation of the bowel but also maintaining homeostasis of intestinal function. Therefore, an ordinary skilled artisan would have been motivated with reasonable expectation of success to combine the teachings of the cited prior art in order to arrive at the claimed invention, for the reasons mentioned above and previously discussed in the 103 rejection.
In response to applicant’s argument, i.e., combining Feuerstein with Suzuki requires hindsight, it is found unpersuasive.
If Applicant means to suggest that the Examiner arrived at the instantly claimed invention via the use of improper hindsight, this is not persuasive because any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Applicant fails to identify a single aspect of the claimed invention that was not taught, disclosed, or suggested by the prior art relied upon by the Examiner.
Accordingly, the 35 U.S.C 103 rejection is maintained as Applicants’ arguments are found unpersuasive.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CLAUDIA ESPINOSA/ Patent Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654