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 .
Claim Status
The claim amendments filed 12/8/25 are acknowledged. Claims 16, 18, and 21-25 are cancelled. New claims 26-27 are added. Claims 1, 4-6, 8-13, 15, 17, and 19-20 are amended. Claims 1-15, 17, 19-20, and 26-27 are currently under consideration for patentability under 37 CFR 1.104.
Withdrawn Objections
The objection to the disclosure because it contains an embedded hyperlink and/or other form of browser-executable code on pages 16 and 30 is withdrawn in light of Applicant’s amendments thereto.
The objection to claim 1 because of the following informalities: the term “IFNλ” contains an acronym and/or abbreviation that should be spelled out upon first occurrence is withdrawn in light of Applicant’s amendments thereto.
The objection to claim 13 because of the following informalities: the terms “Lgr5”, “Ascl2”, and “Smoc2” contains an acronym and/or abbreviation that should be spelled out upon first occurrence is withdrawn in light of Applicant’s amendments thereto.
Maintained Objections
Abstract
The abstract of the disclosure is objected to because the germ “GVHD” is an acronym and/or abbreviation that should be spelled out upon first occurrence. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Applicant provided an amended abstract, however the abstract was not presented on a separate sheet as required by 37 CFR 1.72. Applicant should file the amended abstract on a separate sheet to overcome the objection.
New Objections
Claim Objections
Claim 20 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Withdrawn Claim Rejections
The rejection of claims 1-15, 17, and 19-20 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 24-25 is rendered moot by cancellation of the claim.
The rejection of claims 4-6, 9, 11-15, 17, and 20 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 is withdrawn in light of Applicant’s amendments thereto. The rejection of claim 25 is rendered moot by cancellation of the claim.
Maintained Claim Rejections
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Enablement
The rejection of claims 1-10 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for promoting survival and/or proliferation of an intestinal cell with PEG-rIL-29 and preventing GVHD with PEG-rIL-29, does not reasonably provide enablement for promoting survival and/or proliferation of intestinal cells with any agent except PEG-rIL-29, or treatment or prevention of any other gastrointestinal disease, condition or disorder with any of the encompassed agents except PEG-rIL-29 is maintained. The rejection of claims 11-15, 17, and 19-20 is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 24 and 25 is rendered moot by cancellation of the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
It is noted that MPEP 2164.03 teaches 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 of the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The amount of guidance or direction refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as how to make and use the invention in order to be enabling.”
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)):
1) nature of the invention;
2) the breadth of the claims;
3) the state of the prior art;
4) the level of one of ordinary skill;
5) the level of predictability in the art;
6) the amount of direction or guidance provided by the inventor;
7) the existence of working examples; and
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
1) nature of the invention; 2) the breadth of the claims;
The instant claims are drawn to a method of preventing or treating a gastrointestinal disease, disorder, or condition in a subject, including the step of administering to the subject a therapeutically effective amount of a pegylated recombinant interleukin-29. The IL-29 must be able to prevent all of the thousands of the encompassed gastrointestinal diseases, disorders or conditions. The IL-29 must also be able to treat all of the thousands of the encompassed gastrointestinal diseases, disorders or conditions. The claims have been amended to require that the IL-29 must be able to promote survival and/or proliferation of an intestinal cell, such as an intestinal stem cell.
The claims name overly broad genera of gastrointestinal diseases that can be treated or prevented, although the specification does not provide a definitive list of disorders encompassed by the claimed method. However, at the very least, the claims include all infections, all inflammatory intestinal diseases, all autoimmune diseases, all immunotherapy-induced intestinal damage types , all immune deficiencies, all hematological malignancies, all types of chemotherapy and radiation induced intestinal damage, graft versus host disease, and all combinations thereof. The administration can occur prior to, simultaneously with, and or subsequent to a transplant in the subject. The claims further are directed to promoting survival and/or proliferation of an intestinal cell, comprising administering an IFNλ receptor agonist. The method can be performed in vitro or in vivo in a subject. Therefore, hundreds, if not thousands, of disorders are encompassed. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claims are directed. The encompassed disorders are highly heterogeneous at both the molecular and clinical level. Here are some assorted examples:
An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are a large number of diseases encompassed. Some examples include celiac disease, inflammatory bowel disease, autoimmune enteropathy, autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cholangitis. Immunoglobulin G4-related diseases (IgG4-related diseases) constitute a second group of autoimmune gastrointestinal, hepatobiliary and pancreatic illnesses. See generally Kunovsky et al, entire reference (J Clin Med. 2021 Dec 11;10(24):5796).
Inflammatory bowel disease (IBD) refers to a group of lifelong diseases affecting the intestines. The main types of IBD are ulcerative colitis, Crohn's disease, and colitis inflammatory bowel disease.
There are many types of immune deficiency disorder. These disorders can include primary immune deficiency diseases such as: Autoimmune Lymphoproliferative Syndrome (ALPS), APS-1 (APECED), BENTA Disease, Caspase Eight Deficiency State (CEDS), CARD9 Deficiency and Other Syndromes of Susceptibility to Candidiasis, Chronic Granulomatous Disease (CGD), Common Variable Immunodeficiency (CVID), Congenital Neutropenia Syndromes, CTLA4 Deficiency, DOCK8 Deficiency, GATA2 Deficiency, Glycosylation Disorders with Immunodeficiency, Hyper-Immunoglobulin E Syndromes (HIES), Hyper-Immunoglobulin M Syndromes, Interferon Gamma, Interleukin 12 and Interleukin 23 Deficiencies, Leukocyte Adhesion Deficiency (LAD), LRBA Deficiency, PI3 Kinase Disease, PLCG2-associated Antibody Deficiency and Immune Dysregulation (PLAID), Severe Combined Immunodeficiency (SCID), STAT3 Dominant-Negative Disease, STAT3 Gain-of-Function Disease, Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome, Wiskott-Aldrich Syndrome (WAS), X-Linked Agammaglobulinemia (XLA), X-Linked Lymphoproliferative Disease (XLP), XMEN Disease. Additionally, secondary immunodeficiency can occur where the immune system is weakened due to external environment or illness, and is more common than primary immunodeficiency. Common causes include HIV infection, certain cancers (like leukemia and lymphoma), malnutrition, metabolic disorders, burns, splenectomy, GVHD, autoimmune disease, aging, and immunosuppressive treatments such as chemotherapy or radiation.
D. Diseases that occur as a result of infections with virus, bacteria, fungus, or other pathogens generate inflammatory disorder symptoms such as skin rashes, fever, chills, fatigue, loss of energy, headaches, loss of appetite, muscle stiffness, insomnia, itchiness, stuffy nose, sneezing, and coughing. There are millions of possible infections that may be encompassed. Bacterial infection examples with inflammatory symptoms include Escherichia coli and Salmonella cause food poisoning,
Helicobacter pylori causing gastritis and ulcers, Neisseria meningitidis causing meningitis, Staphylococcus aureus causing a variety of infections in the body, including boils, cellulitis, abscesses, wound infections, toxic shock syndrome, pneumonia, and food poisoning, and Streptococcal bacteria cause a variety of infections in the body, including pneumonia, meningitis, ear infections, and strep throat. Viral infections can include, for example, chickenpox, influenza, herpes, infectious mononucleosis, mumps, measles, rubella, viral gastroenteritis (stomach flu), viral hepatitis, viral meningitis, and viral pneumonia,
E. The claims also encompass other etiologically diverse disorders such as hematological malignancies, GVHD, and various types of therapy induced intestinal damage.
3) the state of the prior art; 5) the level of predictability in the art;
While the state of the art is relatively high with regard to the treatment of specific gastrointestinal disorder types, the state of the art with regard to broadly treating or preventing all gastrointestinal disorders is underdeveloped. For example, there is no known agent that is effective against all inflammatory disorders. The inflammatory disease art involves a very high level of unpredictability. While the state of the art is relatively high with regard to the treatment of specific disorders with specific agents, it has long been underdeveloped with regard to the treatment of all inflammatory diseases. The lack of significant guidance from the present specification or prior art with regard to the actual treatment of all inflammatory diseases in a subject, with the claimed genus of antibodies makes practicing the claimed invention unpredictable.
Predicting whether or not an agent will be able to treat a particular disease is fraught with obstacles, even if the patient population has a well-understood disease. As taught by Ma (Modern Drug Discovery 2004, 7(6)), any results from in vitro screening often poorly correlate with in vivo results because the complicated physiological environment is absent in the in vitro system (see page 30, left column).
In addition, predicting the success of a treatment for such a wide array of diseases presents challenges beyond initial screening. For example, regarding autoimmune disease, according to Steinman et al (Nat Med. 2012 Jan 6;18(1):59-65), there are no approved clinical tests that are effective at predicting the therapeutic success or toxicity of treatments for autoimmune diseases (see page 59). Further Steinman et al teach that a single therapeutic strategy is probably not suitable for all autoimmune diseases or even for individual subsets of patients within one diagnostic category, as there may be heterogeneous biology underlying some of these clinical entities (see page 61). Steinman et al give the example of biologics targeting TNF and its receptors, which are effective in rheumatoid arthritis, Crohn's disease and psoriasis, but which cause marked worsening of disease in multiple sclerosis (see page 60). Blumberg et al (Nat Med.; 18(1): 35–41) teach that one of the greatest problems in translating therapies into clinical practice in autoimmunity are the numerous failures that have been the results of clinical trials. Despite the rapid progress that has been made in understanding the immune system, most of the underlying data has come from animal models, which necessarily only partially represent what is observed in humans. To compound this limitation, there exists no standardized definition of the normal human immune system, no comprehensive understanding of how this normal system is altered in autoimmune diseases and no understanding of the relationship between these immunophenotypic characteristics and either the genetic composition of the host or the environmental stimuli that either promote or protect from the development of autoimmunity (see pages 1-3). It is important to remember that the claims are even broader than the field of autoimmune disorders, including diseases such as, for example, infections, cancers, inflammatory bowel diseases, GVHD, and other disease types, which are beyond the scope of autoimmune disorders.
The prevention and treatment of other gastrointestinal disorders is also unpredictable. For example, treatment or prevention of inflammatory bowel diseases is highly unpredictable. According to Cutter (“Redefining Success in IBD Drug Discovery with Human Tissue Models” REPROCELL Blog, published 12/11/24; downloaded from https://www.reprocell.com/blog/biopta/redefining-success-in-ibd-drug-discovery-with-human-tissue-models on 8/5/25), despite the recent scientific advances in therapies for IBD, including ulcerative colitis and Crohn’s disease, there are still persistent unmet medical needs due to the complexity and chronic nature of these conditions (see Cutter, entire reference). There are many challenges when it comes to managing IBD effectively, due to its multifaceted nature (see Cutter, entire reference). Unlike single-pathway diseases, IBD can be triggered by a variety of different causes, and even a mix of more than one, including environmental factors, imbalances within the gut, genetics and more (see Cutter, entire reference). Researchers have been hard at work expanding the therapeutic armamentarium2 for IBD and related issues, but there still seems to be a ‘therapeutic ceiling;’ a plateau of clinical remission rates that persists around 20-30% (see Cutter, entire reference). Honap et al (Nature Reviews Drug Discovery; Volume 23; July 2024; 546–562) agree with this perspective, offering that “Our understanding of disease pathogenesis is still limited. In addition, there is wide population-level phenotypic heterogeneity in clinical presentation, anatomical involvement, disease behaviour, clinical course and response to treatment” (see Honap, page 547, right column). Other challenges include lack of predictive biomarkers, animal models having poor external validity, variable disease penetrance and delayed disease onset in knockout models, high clinical trial failure rate (see e.g. Honap, Figure 1).
Drug discovery and prevention and treatment of GVHD is also unpredictable in the art. As taught by Flinn et al (Faculty Reviews 2023 12:(4)). Acute and chronic graft-versus-host disease (GVHD) continue to present a significant challenge to physicians, accounting for considerable hematopoietic stem cell transplant (HSCT)-related morbidity and mortality (see Flinn et al, abstract). A challenge to physicians is predicting the trajectory of the GVHD course to allow a risk-stratified management approach and pre-emptive therapy for individual patients to improve outcomes (see e.g. Flinn, page 6, left column). Even when GVHD is controlled by corticosteroids, many patients have adverse side effects and die from infections related to immunosuppression. Barriers to progression in managing patients with SR-GVHD include the inability to accurately risk-stratify, an incomplete understanding of the pathophysiology behind corticosteroid resistance, a deficiency of high-quality evidence to determine optimal treatment strategies, and the difficulties in comparing strategies because of heterogeneity in many factors, including patients, donors and conditioning regimens (see e.g. Flinn, page 6, right column). Amanam et al (Hematology Am Soc Hematol Educ Program (2023) 2023 (1): 164–170) teach that a significant obstacle to evaluating the response of novel GVHD - directed therapies has been standardized response assessments (see Amanam, abstract). This has functioned as a barrier to designing and interpreting clinical trials that are structured around the treatment of cGVHD (see Amanam, abstract).
Given the extremely broad nature of the encompasses diseases, which have variable etiology and pathology, and the teachings of the references named above, one of skill in the art would not be able to predict the effectiveness of the encompassed agonists to prevent and treat each of the claimed gastrointestinal diseases.
Further, in vitro and animal model studies have not correlated well with in vivo clinical trial results in patients. Since the therapeutic indices of immunosuppressive drugs or biopharmaceutical drugs can be species- and model-dependent, it is not clear that reliance on the in vitro and in vivo experimental observations, as well as the clinical experience, accurately reflects the relative ability or efficacy of the claimed methods to prevent or treat the encompassed gastrointestinal diseases. Regarding in vivo methods which rely on previously undescribed and generally unpredictable mechanisms, ''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). The “amount of guidance or direction'' refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03).''
Further, in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), the court states “[W]here there is “no indication that one skilled in [the] art would accept without question statements [as to the effects of the claimed drug products] and no evidence has been presented to demonstrate that the claimed products do have those effects,” an applicant has failed to demonstrate sufficient utility and therefore cannot establish enablement” and “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the “inventor” would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”
6) the amount of direction or guidance provided by the inventor; 7) the existence of working examples:
The instant specification provides an example of administration of a single encompassed agonist to a subject. The example administered PEGylated recombinant IL-29 (PEG-rIL-29) to wild type mice and assessed ability of PEG-rIL-29 to support the gastrointestinal stem cell compartment through generation of colon organoids (see e.g. page 35 of the instant specification). The example also included the prevention of GVHD with PEG-rIL-29 in mice with or without GVHD (see e.g. page 38, instant specification). PEG-rIL-29 was not shown to influence leukemia growth or death in allograft recipients (see e.g. page 38 of the instant specification). However, no administration demonstrated treatment of any encompassed disease or disorder. Therefore, one of skill in the art would have been required to engage in undue experimentation to match the pegylated IL-29 with the appropriate disease that could be treated and/or prevented by the agonist. This experimentation would require testing the IL-29 against hundreds of possible diseases to identify a match for therapy. This amount of experimentation would be an undue burden.
In conclusion, the claimed invention does not provide enablement for the entire scope of the rejected claims. Thus for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Applicant’s Arguments
Applicant argues:
1. The claims have been amended to specify that the interferon agonist is pegylated recombinant IL-29 and claim one has been amended to recite that the IL-29 promotes survival and/or proliferation of an intestinal cell. In light of the amendments, the specification provides adequate enablement.
Applicant’s arguments have been fully considered and are not persuasive for the following reasons:
1. The rejection has been updated to reflect current claim amendments. Applicant has not amended the claims to recite a method of promoting survival and/or proliferation of an intestinal cell. Instead, the amendment only adds additional requirements to the IL-29, without addressing the treatment and/or prevention claims. Applicant’s own claims appear to separate the two functions by requiring that the administered IL-29, which is intended to treat or prevent disease, also must perform the separate function of promoting survival and/or proliferation of an intestinal cell. Therefore, the rejection is maintained.
Claim interpretation
The claims recite “preventing or treating a gastrointestinal disease, disorder, or condition”. The instant specification defines “preventing” to "preventing", "prevent" or "prevention" refers to therapeutic intervention, course of action or protocol initiated prior to the onset of the gastrointestinal disease, disorder or condition and/or a symptom thereof so as to prevent, inhibit or delay or development or progression of the gastrointestinal disease, disorder or condition or the symptom” (see instant specification page 9). Further the claims refer to administration “prior to” transplant, without actually requiring any transplant to occur. The claims will therefore be interpreted to read on administration of pegylated IL-29 to any individual, because administration to any individual not having a gastrointestinal disease, disorder, or condition will inherently be preventative, and prior to a transplant, while administration to an individual with a gastrointestinal disease, disorder, or condition will inherently provide treatment.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claim(s) 1-15, 17, and 26-27 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Doyle et al (US 7,351,689 B2; filed 7/29/05; published 4/1/08), as evidenced by Kim et al (Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3932-7. Epub 2012 Feb 21) is maintained. The rejection of claims 19-20 is withdrawn in light of Applicant’s amendments to claim 19. The rejection of claims 24-25 is rendered moot by cancellation of the claims.
The instant claims are directed to a method of preventing or treating a gastrointestinal disease, disorder or condition in a subject, said method including the step of administering to the subject a therapeutically effective amount of a pegylated IL-29 to thereby prevent or treat the gastrointestinal disease, disorder or condition in the subject. The gastrointestinal disease, disorder or condition can be at least partly characterized by gastrointestinal epithelial damage and/or loss. The gastrointestinal disease, disorder or condition can be selected from the group consisting of an inflammatory intestinal disease, an infection, an autoimmune disease, immunotherapy-induced intestinal damage, an immune deficiency, a hematological malignancy, chemotherapy- induced intestinal damage, radiation-induced intestinal damage, graft versus host disease (GVHD), and any combination thereof. The GVHD can be acute and/or chronic GVHD. The GVHD can comprise intestinal and/or colonic epithelial damage and/or loss. The subject can be or has been administered an immunosuppressive agent. The receptor agonist does not modulate and/or preserves graft versus leukemia (GVL) and/or graft versus tumor (GVT) effects of the transplant. The claims are further directed to a method of promoting survival and/or proliferation of an intestinal cell, said method including the step of contacting the intestinal cell with a pegylated IL-29 under conditions to promote survival and/or proliferation of the intestinal cell. The intestinal cell can comprise an intestinal stem cell. The intestinal stem cell can be positive for or express one or more of Lgr5, Ascl2 and Smoc2. The method can be performed in vitro or in vivo in a subject. The pegylated IL-29 can be administered prior to, simultaneously with and/or subsequent to administration of a cytotoxic agent to the subject. The cytotoxic agent can be a chemotherapeutic agent and/or a radiotherapy. The disease can be an inflammatory intestinal disease among others listed in instant claim 27.
Regarding the limitations of instant claim 1-4, Doyle teaches methods for treating cancer and autoimmune disorders using IL-29, as a monotherapy or in combination with other therapeutic agents (see e.g. abstract). The Il-29 can be prepared as a pegylated protein (see e.g. column 28, lines 18-29). The disease can be inflammatory bowel disease (see e.g. column 50, lines 19-41), which is recited in the instant specification as an autoimmune disease that falls within the instant claim scope (see instant specification page 11). Doyle teaches that administration of IL-29 inhibition of the autoimmune response associate with IBD is demonstrated in IBD models such as the graft versus host disease (GVHD) intestinal inflammation models (see e.g. column 51, lines 20-30).
Regarding the limitations of instant claims 1-6, the claims recite “preventing or treating a gastrointestinal disease, disorder, or condition”. The instant specification defines “preventing” to "preventing", "prevent" or "prevention" refers to therapeutic intervention, course of action or protocol initiated prior to the onset of the gastrointestinal disease, disorder or condition and/or a symptom thereof so as to prevent, inhibit or delay or development or progression of the gastrointestinal disease, disorder or condition or the symptom” (see instant specification page 9). The administration of pegylated IL-29 to an individuals will inherently be a preventative treatment. Doyle teaches methods for treating cancer and autoimmune disorders using IL-29, as a monotherapy or in combination with other therapeutic agents (see e.g. abstract), and therefore anticipate prevention of the instant claims’ named diseases, conditions or disorders. Further, the instant specification states that inflammatory bowel disease is characterized by intestinal damage, such as linear ulcers, stricture, fistulas, and other types of intestinal damage (see instant specification page 11). Doyle teaches methods for treating cancer and autoimmune disorders using IL-29, as a monotherapy or in combination with other therapeutic agents (see e.g. abstract). The disease can be inflammatory bowel disease (see e.g. column 50, lines 19-41), which is recited in the instant specification as an autoimmune disease that falls within the instant claim scope (see instant specification page 11).
Regarding the limitations of instant claim 7, Doyle teaches that the IL-29 can be administered with other agents such as REMICADE and others (see e.g. column 52, lines 58-67). The instant specification defines “immunosuppressive agent” to include REMICADE (see instant specification page 13).
Regarding the limitations of instant claim 8-10, Doyle teaches that administration of IL-29 inhibition of the autoimmune response associate with IBD is demonstrated in IBD models such as the graft versus host disease (GVHD) intestinal inflammation models (see e.g. column 51, lines 20-30). Further, the claims do not actually require a transplant to occur, but only that the IL-29 is administered “prior to” a transplant. The instant specification also indicates that administration of IL-29 inherently does not modulate GVL or GVT (see e.g. instant specification page 2).
Regarding the limitations of instant claims 11-12, 14, 17, and 27, Doyle teaches methods for treating cancer and autoimmune disorders using IL-29, as a monotherapy or in combination with other therapeutic agents (see e.g. abstract). The Il-29 can be prepared as pegylated proteins (see e.g. column 28, lines 18-29). The disease can be inflammatory bowel disease (see e.g. column 50, lines 19-41), which is recited in the instant specification as an autoimmune disease that falls within the instant claim scope (see instant specification page 11). Doyle teaches that administration of IL-29 inhibition of the autoimmune response associate with IBD is demonstrated in IBD models such as the graft versus host disease (GVHD) intestinal inflammation models (see e.g. column 51, lines 20-30). Systemic administration and administration by intralesional application (see e.g. column 32, lines 14-49) would inherently contact all cells in the body, including intestinal cells, and intestinal stem cells, which are inherently found in intestinal crypts.
Regarding the limitation of instant claims 12 and 13, Doyle teaches that administration of IL-29 inhibition of the autoimmune response associate with IBD is demonstrated in IBD models such as the graft versus host disease (GVHD) intestinal inflammation models (see e.g. column 51, lines 20-30). Systemic administration and administration by intralesional application (see e.g. column 32, lines 14-49) would inherently contact all cells in the body, including intestinal cells, and intestinal stem cells, which are inherently found in intestinal crypts. As evidenced by Kim, lifelong renewal of adult intestinal epithelium requires activation of stem cells in mucosal crypts (see e.g. Kim, abstract). Lgr5 is a molecular marker of crypt-cell populations that replenish cells over time, and hence function as stem cells (see e.g. abstract). Therefore, treatment or prevention of an IBD would inherently contact cells such as those that express Lgr5 during treatment.
Regarding the limitation of instant claim 15 and 26, Doyle teaches that the IL-29 can be administered with chemotherapy, radiation therapy or other types of therapies (see e.g. column 3, lines 25-32).
Applicant’s Arguments
Applicant argues:
1. Doyle is primarily focused on immunomodulation, anti-inflammatory effects and prevention of disease. Applicant notes that Doyle fails to teach administration to any subject in need of treatment or prevention of gastrointestinal disease.
2. Doyle does not teach that the administration would necessarily promote survival and/or proliferation of an intestinal cell.
Applicant’s arguments have been fully considered and are not persuasive for the following reasons:
1. Doyle meets the limitations required by the claims. The instant claims are directed to “preventing…a gastrointestinal disease, disorder or condition in a subject”. There is no requirement in the instant claims that a subject is “in need thereof.” Additionally, there is no definition in the instant specification for “in need thereof.” Applicant has not provided criteria to identify those in need thereof. The instant specification defines “preventing” to "preventing", "prevent" or "prevention" refers to therapeutic intervention, course of action or protocol initiated prior to the onset of the gastrointestinal disease, disorder or condition and/or a symptom thereof so as to prevent, inhibit or delay or development or progression of the gastrointestinal disease, disorder or condition or the symptom” (see instant specification page 9). Therefore, the specification indicates that administration to any individual prior to the onset of any of the encompassed diseases would constitute prevention.
2. As stated in MPEP 2112, "[T]he discovery of a previously unappreciated property of a prior art composition, or of 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). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). Systemic administration and administration by intralesional application (see e.g. Doyle column 32, lines 14-49) would inherently contact all cells in the body, including intestinal cells, and intestinal stem cells, which are inherently found in intestinal crypts. There is no way to separate the functions of the drug once it has entered the body. The intestine inherently requires continual renewal of the intestinal epithelium as evidenced by Kim. This lifelong renewal of adult intestinal epithelium inherently requires activation of stem cells in mucosal crypts, indicating that intestinal stem cells are inherently present in the intestines (see e.g. Kim, abstract). These cells necessarily possess specific gene expression that creates the stem-like behavior. This gene expression can be detected with specific marker, such as Lgr5. Lgr5 is a molecular marker of crypt-cell populations that replenish cells over time, and hence function as stem cells (see e.g. Kim abstract). Therefore, treatment or prevention of an IBD would inherently contact intestinal stem cells upon administration, which will express Lgr5 due to their function as stem cells. For these reasons and the reasons set forth above, the rejection is maintained.
New Claim Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-8, 10-14, and 19 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Hausman et al (WO 2009/149377 A1; filed 6/5/09; published 12/10/09) as evidenced by Kim et al (Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3932-7. Epub 2012 Feb 21).
The instant claims are directed to a method of preventing or treating a gastrointestinal disease, disorder or condition in a subject, said method including the step of administering to the subject a therapeutically effective amount of a pegylated IL-29 to thereby prevent or treat the gastrointestinal disease, disorder or condition in the subject. The gastrointestinal disease, disorder or condition can be at least partly characterized by gastrointestinal epithelial damage and/or loss. The gastrointestinal disease, disorder or condition can be selected from the group consisting of an inflammatory intestinal disease, an infection, an autoimmune disease, immunotherapy-induced intestinal damage, an immune deficiency, a hematological malignancy, chemotherapy- induced intestinal damage, radiation-induced intestinal damage, graft versus host disease (GVHD), and any combination thereof. The GVHD can be acute and/or chronic GVHD. The GVHD can comprise intestinal and/or colonic epithelial damage and/or loss. The subject can be or has been administered an immunosuppressive agent. The receptor agonist does not modulate and/or preserves graft versus leukemia (GVL) and/or graft versus tumor (GVT) effects of the transplant. The claims are further directed to a method of promoting survival and/or proliferation of an intestinal cell, said method including the step of contacting the intestinal cell with a pegylated IL-29 under conditions to promote survival and/or proliferation of the intestinal cell. The intestinal cell can comprise an intestinal stem cell. The intestinal stem cell can be positive for or express one or more of Lgr5, Ascl2 and Smoc2. The method can be performed in vitro or in vivo in a subject. The pegylated IL-29 can be administered prior to, simultaneously with and/or subsequent to administration of a cytotoxic agent to the subject. The cytotoxic agent can be a chemotherapeutic agent and/or a radiotherapy. The disease can be an inflammatory intestinal disease among others listed in instant claim 27.
Regarding the limitations of instant claim 1-6, Hausman teaches methods for treating a human patient infected with or at risk of infection with the hepatitis C virus comprising administering to the patient a therapeutically effective amount of pegylated Type III interferon (see e.g. claim 1). The type III pegylated interferon can be IL-29 (see e.g. claim 4). The patients can be patients awaiting or following liver transplant (see e.g. claim 12). The instant claims recite “preventing or treating a gastrointestinal disease, disorder, or condition”. The instant specification defines “preventing” to "preventing", "prevent" or "prevention" refers to therapeutic intervention, course of action or protocol initiated prior to the onset of the gastrointestinal disease, disorder or condition and/or a symptom thereof so as to prevent, inhibit or delay or development or progression of the gastrointestinal disease, disorder or condition or the symptom” (see instant specification page 9). Furthermore, instant specification page 1 states that graft versus host disease (GVHD) is encompassed by the term “gastrointestinal diseases, disorders or conditions.” The instant specification indicates that GVHD can occur after transplant. The administration of pegylated IL-29 to an individual’s awaiting or following a transplant will inherently be a preventative treatment for GVHD.
Regarding the limitations of instant claim 7, Hausman teaches that the subject can be administered anti-inflammatory drugs (see e.g. claim 15), which according to instant specification page 13 would be encompassed as “immunosuppressive agents.”
Regarding the limitations of instant claim 8 and 10, Hausman teaches methods for treating a human patient infected with or at risk of infection with the hepatitis C virus comprising administering to the patient a therapeutically effective amount of pegylated Type III interferon (see e.g. claim 1). The type III pegylated interferon can be IL-29 (see e.g. claim 4). The patients can be patients awaiting or following liver transplant (see e.g. claim 12).
Regarding the limitation of instant claims 11-14, Hausman teaches methods for treating a human patient infected with or at risk of infection with the hepatitis C virus comprising administering to the patient a therapeutically effective amount of pegylated Type III interferon (see e.g. claim 1). The type III pegylated interferon can be IL-29 (see e.g. claim 4). The patients can be patients awaiting or following liver transplant (see e.g. claim 12). The administration can be intravenously, intramuscularly, or through other routes (see e.g. claim 48). Systemic administration would inherently contact all cells in the body, including intestinal cells, and intestinal stem cells, which are inherently found in intestinal crypts. As evidenced by Kim, lifelong renewal of adult intestinal epithelium requires activation of stem cells in mucosal crypts (see e.g. Kim, abstract). Lgr5 is a molecular marker of crypt-cell populations that replenish cells over time, and hence function as stem cells (see e.g. abstract). Therefore, treatment or prevention of an IBD would inherently contact cells such as those that express Lgr5 during treatment.
Conclusion
No claim is 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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/ANDREA K MCCOLLUM/Examiner, Art Unit 1674
/BRIAN GANGLE/Primary Examiner, Art Unit 1645