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 .
Priority
The instant application is claiming the benefit as a 35 U.S.C. 371 national phase application from, and claims priority to, International Application No. PCT/US2020/049073, filing date 9/2/2020, which claims the benefit of the prior-filed United States Provisional Patent Application No. 62/895,179, filing date 9/3/2019.
Status of Application/Claims
The amendment, filed 10/07/2025, is acknowledged. Claims 2-3 are canceled. Claims 1, 4-5, 8-9, 11-17, and 19 are currently amended. Claims 1 and 4-20 are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/07/2025 has been fully considered by the examiner.
Withdrawn Objections/Rejections
Regarding the specification objection for improper use of trademarks/trade names, applicant amendment has addressed the issue. Thus, the objection is withdrawn.
Regarding the specification objection for informalities, applicant amendment has addressed the issue. Thus, the objection is withdrawn.
Regarding the claim 9, 11-12, and 19 objections for informalities, applicant amendment has addressed the issues for claims 9 and 11-12 and has partially addressed the objection for claim 19. Thus, the objections for claims 9 and 11-12 are withdrawn. See maintained objection for claim 19 below.
Regarding the rejections for claims 2-5, 8, 13-17, and 19 under 35 U.S.C. 112(b) for indefiniteness: Applicant amendment has fully addressed the rejections for claims 2-5, 8, 13-14, 16, and 19 and has partially addressed the rejections for claims 15 and 17. Thus, the rejections for claims 2-5, 8, 13-17, and 19 are withdrawn. See maintained rejections for claims 15 and 17 below.
Regarding the rejection for claims 1, 6-7, 11, and 18-20 under 35 U.S.C. 102 for novelty, applicant arguments (submitted 10/07/2025) have been fully considered and are persuasive; thus, the rejections are withdrawn. (See new 35 U.S.C. 103 rejection below.)
Regarding the rejection for claims 2-5, 8-10, and 12-17 under 35 U.S.C. 103 for obviousness, applicant arguments (submitted 10/07/2025) have been fully considered and are persuasive; thus, the rejections are withdrawn. See new 35 U.S.C. 103 rejection below.
Claim Objections
Claim 19 is objected to because of the following informalities: The following limitations are written in duplicate within the claim: acute endotoxemia, metabolic syndrome, sepsis, acute kidney injury, and acute pancreatitis.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 15 and 17 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 15 recites the limitation “the human IgG1” but is dependent on claim 14 which recites “the human IgG1 Fc”. There is insufficient antecedent basis for this limitation in the claim.
Claim 17 recites the limitation “human IL-22 portions of said protein” but is dependent on claim 12 which recites “said IL-22 protein”. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Scheer, et al. US10160793B2. Publication date: 10/23/2014, Effective filing date: 03/15/2013 (herein referred to as Scheer-2013; new reference); and, further in view of Xie, et al. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J. Biol. Chem. (2000), 275: 40, p.31335-31339; NP_065386.1 (herein referred to as Xie).
Scheer-2013 teaches IL-22 polypeptides, IL-22 Fc fusion proteins, and IL-22 agonists for methods of treating inflammatory bowel disease and other inflammatory conditions (title; abstract; p.108, col.65, paras.4-5 – p.110, col.69, paras.2-3).
Scheer-2013 does not teach that the IL-22 protein has at least 90% identity to SEQ ID NO: 2 (instant claim 12).
[AltContent: textbox (Sequence Alignment: Xie 2000 human IL-22 vs. Applicant SEQ ID NO: 2 [img-media_image1.png])]Xie teaches the human amino acid sequence for IL-22, which shows 100% overlap with applicant SEQ ID NO: 2 (Figure 1A; also, see sequence alignment below):
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Scheer-2013 with the teachings of Xie by using the human IL-22 amino acid sequence (taught by Xie) as the IL-22 protein sequence for the Fc-fusion protein (as taught by Scheer-2013). One of ordinary skill in the art would have a reasonable expectation of success because Xie teaches a human IL-22 amino acid sequence that overlaps 100% with instant human IL-22 SEQ ID NO: 2.
Claims 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Scheer-2013 and Xie, as applied to instant claim 12; and, in further view of Scheer, et al. US20180355009A1). Publication date: 12/13/2018, Effective filing date: 03/15/2013 (herein referred to as Scheer, as referenced in office action submitted 04/09/2025).
The combination of Scheer-2013 and Xie teaches an Fc-fusion IL-22 protein that has 100% identity to instant human IL-22 SEQ ID NO: 2.
The combination of Scheer-2013 and Xie does not teach that the Fc is a human IgG1 Fc (instant claim 13); that the Fc comprises one or more mutations that alter Fc effector function (instant claim 14); that the human IgG1 Fc comprises a substitution at N297 (instant claim 15); that the N297 mutation is N297G (instant claim 16); or that a linker connects the Fc and human IL-22 (instant claim 17).
Scheer teaches IL-22 Fc fusion proteins, compositions thereof, and methods of use for inflammatory bowel diseases (IBDs; abstract), including Crohn’s disease and ulcerative colitis (p.1, [0006]). Scheer teaches that the Fc can be human IgG1 Fc (p.2, [0013], p.13, [0138], p.18, [0195]). Scheer teaches an Fc mutation wherein the N297 amino acid residue is changed to a glycine (i.e., N297G) or alanine (p.1, [0010]). Scheer also teaches an IL-22 polypeptide linked to an Fc region by a linker (p.1, [0010]).
Further, Scheer teaches that increased expression of IL-22 is observed with IBDs (p.1, [0006], and that “…an Fc variant that possesses some but not all effector functions (i.e., mutations that alter effector function), which make it a desirable candidate for applications in which the half-life of the antibody or a fusion protein comprising an Fc region in vivo is important yet certain effector functions (such as complement and ADCC) are unnecessary or deleterious” (p.13, [0139]). Scheer also teaches that the N297G mutation prevents attachment of the normal core sugar (p.19, [210] and that “N-glycosylation of the Fc is important for binding to FcγR” (p.6, [0053]) which can affect antibody-dependent cellular cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Scheer-2013 and Xie with the teachings of Scheer by linking the IL-22 polypeptide to the Fc of the Fc-fusion protein (taught by Scheer-2013 and Xie) using a linker (as taught by Scheer) and to mutate the Fc region to comprise an N297G amino acid substitution (as taught by Scheer), to arrive at the instantly claimed invention, in order to receive the benefit of retaining some effector function while preventing attachment of the core sugar and binding FcγR which can exhibit deleterious effects on ADCC or CDC. One of ordinary skill in the art would have a reasonable expectation of success because Scheer-2103 and Scheer both teach Fc-fusion proteins of IL-22.
Claims 1, 4-11, and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Scheer-2013 and Xie; in further view of Burshtein, et al. WO2016128974A1 (herein referred to as Burshtein); and, in further view of Lee, et al. N-acetylcysteine modulates lipopolysaccharide-induced intestinal dysfunction. Scientific Reports (publication date: 01/30/2019), 9: 1004, p.1-10 (herein referred to as Lee).
The combination of Scheer-2013 and Xie teaches an Fc-fusion IL-22 protein that has 100% identity to instant human IL-22 SEQ ID NO: 2.
Scheer-2013 additionally teaches pharmaceutical compositions comprising Fc/IL-22 fusion proteins that can be formulated for oral administration (title; abstract; )and that can be administered with pharmaceutically acceptable carriers (p.78, col.6, para.6). Scheer-2013 additionally teaches use of the Fc-fusion compositions for the following diseases and conditions: inflammatory bowel disorder, Crohn's disease, ulcerative colitis, Type II diabetes, Type II diabetes with morbid obesity, wounds, diabetic wounds, diabetic ulcers, burns, ulcers, pressure ulcers, venous ulcers, graft versus host disease (GVHD), microbial infection, acute kidney injury, acute pancreatitis, cardiovascular conditions, metabolic syndrome, acute endotoxemia, sepsis, atherosclerosis, cardiovascular disease, mild endotoxemia, acute coronary heart disease, hypertension, dyslipemia, obesity, hyperglycemia, lipid metabolism disorders, hepatitis, acute hepatitis, renal failure, acute renal failure, acute kidney injury, renal graft failure, post cadaveric renal transplant delayed graft function, contrast induced nephropathy, pancreatitis, liver fibrosis, and lung fibrosis (p.80, col.9-10; p.89, col.27; p.92, col.33; p.106, col.62, para.4; p.108-110). Scheer-2013 also teaches the importance of N-glycosylation of the Fc and binding to the FcγR, as well as the specific N297G Fc mutation (p.77, col.4, para.3; p.87, col.23, para.7). Additionally, Scheer-2013 teaches sustained-release preparations including semipermeable matrices of solid hydrophobic polymers containing the IL-22 Fc fusion protein, including films and microcapsules (p.106, col.62, para.2); and, which can be gelatin, hydroxymethylcellulose, or poly-(methylmethacylate) capsules (p.106, col.61, para.7).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date to further combine Scheer-2013 and Xie with the additional teachings of Scheer-2013 by using the IL-22 Fc-fusion protein (taught by Scheer-2013) comprising the human IL-22 SEQ ID NO: 2 (taught by Xie) in a solid, oral, gelatin pharmaceutical composition for the treatment of inflammatory disorders, including inflammatory bowel disorder, Crohn’s disease or ulcerative colitis among others (also taught by Scheer-2013). One of ordinary skill in the art would have a reasonable expectation of success because Xie teaches a human IL-22 amino acid sequence that overlaps 100% with instant human IL-22 SEQ ID NO: 2 and Scheer-2013 teaches that IL-22 Fc fusion proteins can be administered for inflammatory disease treatment.
The combination of Scheer-2013 and Xie does not teach that the pharmaceutical composition comprises an absorption enhancer that is NAC (instant claims 1 and 6); that the absorption enhancer is a salt of NAC, wherein the salt is a monosodium salt (instant claim 8); that the composition further comprises a protease inhibitor (instant claim 9); or, that the composition further comprises EDTA (instant claim 10).
Burshtein teaches compositions of sodium 8-N-(2-hydroxybenzoyl)aminocaprylate)/SNAC (i.e. “NAC”) that also include therapeutically active agents (p.86, claim 1). Burshtein also teaches that the therapeutically active agents can be hormones and/or cytokines (p.63, para.5), including interferons and interleukins (p.65, para.3). Burshtein further teaches use in treatment of conditions “treatable by oral administration” (p.82, para.4), including diabetes and hyperglycemia. Further, Burshtein teaches formulations for oral administration of active agents (title) that include therapeutically active agents and protective agents that include protease inhibitors (abstract). Boone teaches sodium salt forms of absorption enhancers (i.e., SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate), N(10-[2-hydroxybenzoyl]amino)decanoic acid (SNAD), 8-[N-(2-hydroxy-4-25 methoxybenzoyl)amino ]caprylic chlorobenzoyl)amino ]caprylic acid acid (4-MOAC), (5-CNAC) and 8-[N-(2-hydroxy-5-4-[ ( 4-chloro-2-hydroxybenzoyl)amino] butanoic acid (4-CNAB) (p.1, [4-5]). Burshtein also teaches solid oral dosage forms that comprise SNAC or SNAD for “facilitating absorption and/or enhancing bioavailability” (p.1, [6]). Burshtein specifically teaches monosodium SNAC and SNAD forms on p.46. Regarding protease inhibitors, Burshtein teaches that compositions can include serpins, trypsin protease inhibitors (i.e., protein protease inhibitor), chelating agents (e.g., EDTA), cysteine protease inhibitor, threonine protease inhibitors, aspartic acid protease inhibitors, and metalloprotease inhibitors (p.39, [4]-p.43, [1]) for the purpose of serving as a “protective agent” that protects the therapeutically active agent and/or SNAC against enzymes and/or acid in the gastrointestinal tract.
Lee teaches that NAC is known to have beneficial effects in a number of diseases including cancer, haemorrhagic cystitis, and obstructive lung disease, because of its critical role in attenuating oxidative stress, apoptosis, and mitochondrial dysfunction (p.7, para.4). Lee teaches dietary NAC administration following LPS-induced intestinal inflammation, wherein NAC treatment significantly reduced inflammatory gene expression (p.3, para.3; Fig.4B) and oxidative stress (Fig.5). Lee further teaches NAC treatment alleviated intestinal barrier function and wound healing (p.7, para.5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Scheer-2013 and Xie with the teachings of Burshtein and Lee by formulating the IL-22 Fc-fusion protein composition (taught by Scheer-2013 and Xie) to include an absorption enhancer such as NAC monosodium salt (taught by Burshtein), to arrive at the instantly claimed invention, because the combination of prior art elements according to the known methods of reducing intestinal inflammation with IL-22 treatment (as taught by Scheer-2013) and reducing intestinal inflammation/improving barrier function/improving wound healing with NAC (as taught by Lee) via oral delivery would be expected to produce the synergistic result of reducing intestinal inflammation when administering the anti-inflammatory agents in the same composition. One of ordinary skill in the art would have a reasonable expectation of success because Burshtein teaches that monosodium salts of NAC/SNAC (or NAD/SNAD) can be used in compositions with therapeutic agents including cytokines and Scheer-2013 teaches that IL-22 is a cytokine. Further, one of ordinary skill in the art would be motivated to add NAC/SNAC (or NAD/SNAD) to facilitate absorption and/or enhance bioavailability (as taught by Burshtein) as well as to reduce intestinal inflammation, improv3 barrier function, and improve wound healing (as taught by Lee).
It would have been prima facie obvious for one of ordinary skill in the art to also further combine the teachings of Scheer-2013, Xie, Burshtein, and Lee with the additional teachings of Burshtein by modifying the composition to include protease inhibitors, including chelating agents such as EDTA, to arrive at the instantly claimed invention, in order to receive the expected benefit that these agents would serve as protective agents (as taught by Burshtein). One of ordinary skill in the art would have a reasonable expectation of success because Burshtein teaches that formulations comprising protease inhibitors, chelating agents, and/or EDTA can be formulated for oral administration. This would have the predictable result of protecting the therapeutically active agents and absorption enhancers from enzymes and/or acid in the gastrointestinal tract.
Response to Arguments
Regarding the claim 19 objection for informalities pertaining to the following limitations, which were written in duplicate: wounds, acute endotoxemia, metabolic syndrome, sepsis, acute kidney injury, and acute pancreatitis. While applicant amendment has addressed the duplicate issue of the term “wounds,” the duplicate issues for the terms “acute endotoxemia” (lines 6 and 7; i.e., “endotoxemia (acute…” = “acute endotoxemia”), “metabolic syndrome” (lines 6 and 7), “sepsis” (lines 6 and 8), “acute kidney injury” (lines 5 and 9-10), and “acute pancreatitis” (lines 5-6 and 11). Thus, the objection is maintained in modified form.
Regarding the claim 15 and 17 rejections for indefiniteness, applicant amendment has addressed the indefiniteness issues regarding claim dependency, but has not fully addressed the lack of antecedent issues. Claim 15 recites “the human IgG1” but is dependent on claim 14 which recites “the human IgG1 Fc”; and claim 17 recites “human IL-22 portions of said protein” but is dependent on claim 12 which recites “said IL-22 protein”.
Regarding the prior art rejections for claims 1, 6-7, 11, and 18-20 under 35 U.S.C. 102 for novelty and for claims 2-5, 8-10, and 12-17 for obviousness: Claims 2-3 were canceled; thus, the rejections are withdrawn. Regarding the remaining claims, applicant remarks and arguments (submitted 10/07/2025) have been considered and are persuasive. While Boone teaches administration of an Fc-fusion protein and co-administration of IL-22 which is considered under “combination therapies,” Boone does not adequately teach a composition that comprises both an IL-22 protein and NAC. However, new 35 U.S.C. 103 obviousness rejections for claims 1 and 4-20 are provided as the combination of prior art teaches the instant claims.
Conclusion
The instant office action is made non-final due to new rejections not necessitated by amendment.
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647