DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Amendment
2. The amendment filed Jun 2, 2026 has been entered. Claims 37-38, 41, and 43-55 have been cancelled. Claims 36, 39 and 42 have been amended. Claims 56-70 were newly added. Claims 18/ are under consideration in this Office Action.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on June 2m 2026 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawal of Rejections
4. The rejection of claims 36-43 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of Applicants amendments and arguments.
5. The rejection of claims 36-43 under 35 U.S.C. 102(a)(1) and/or (a)(2) as being anticipated by Kim et al., is withdrawn in view of Applicants amendments and arguments.
6. The rejection of claims 37-38, 41 and 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KR20180116925 (published 2018-10-26).
7. The rejection of claims 36-42 under 35 U.S.C. 102(a)(1) and/or (a)(2) as being anticipated by Lee et al., is withdrawn in view of Applicants amendments and arguments.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
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.
8. Claims 36, 39-40, 42, 64-66 and 67-70 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating an immune-related disease in a human, the method comprising administering a therapeutic amount of a helper T cell with an Lrig1 protein to the subject as an active ingredient, does not reasonably provide enablement for a method for the prevention of an immune-related disease in a subject, the method comprising administering a helper T cell with an Lrig1 protein or a gene that encodes an Lrig1 protein to the subject as an active ingredient.
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 or use the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and
Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v.
Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
The claims are drawn to a method for the prevention or treatment to an immune-related disease in a subject in need thereof, the method comprising administering a helper T cell with an Lrig1 protein or a gene that encodes an Lrig1 protein to the subject as an active ingredient. Claims 39, 57-59, 61-66, and 68-69 wherein the immune-related disease is at least one selected from the group consisting of autoimmune disease, graft-versus-host disease, organ transplant rejection, asthma, atopy, and acute or chronic inflammatory disease. Claim 40 recites wherein the autoimmune disease is at least one selected from the group consisting of rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, atopic dermatitis, psoriasis, alopecia areata, asthma, Crohn's disease, Behcet's disease, Sjogren's syndrome, Guillain-Barre syndrome, chronic thyroiditis, multiple sclerosis, multiple myositis, ankylosing spondylitis, fibroblast and nodular multiple arteritis.
The claims are broad and inclusive of all types of a conditions selected from any type of immune-related disease in humans generally. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claims are directed. The claims are extremely broad due to the vast number of immune-related diseases represented by the phrase “preventing or treating” an immune-related disease in a subject in need thereof cancer in a subject in need thereof. There is no prevention of immune-related disease such as autoimmune disease, graft-versus-host disease, organ transplant rejection, asthma, atopy, acute or chronic inflammatory disease, rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, atopic dermatitis, psoriasis, alopecia areata, asthma, Crohn's disease, Behcet's disease, Sjogren's syndrome, Guillain-Barre syndrome, chronic thyroiditis, multiple sclerosis, multiple myositis, ankylosing spondylitis, fibroblast and nodular multiple arteritis.
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
While the state of the art is relatively high with regard to the treatment of specific immune related diseases, the state of the art with regard to preventing any type of immune-related disease is underdeveloped. In particular, there is no known single anti-immune-related disease agent that is effective against all immune-related disease types. The autoimmune disease treatment art involves a very high level of unpredictability. While the state of the art is relatively high with regard to the prevention or treatment of specific immune diseases with specific agents with specific agents, it has long been underdeveloped with regard to the prevention of autoimmune diseases broadly. The lack of significant guidance from the present specification or prior art with regard to the actual prevention of all autoimmune diseases and in any subject, including a human subject, with the claimed “agent” makes practicing the claimed invention unpredictable.
One cannot prevent any type of immune disease from forming in any type of subject or even in a human subject. While there is no guaranteed way to prevent autoimmune diseases, as they often result from complex interactions between genetics and environment, you can reduce your risk by managing chronic stress, eating a nutrient-dense anti-inflammatory diet, avoiding smoking, getting regular exercise, and reducing exposure to toxins. See https://my.clevelandclinic.org/health/diseases/21624-autoimmune-diseases, 2024. Systemic lupus erythematosus (SLE) cannot be currently prevented as its causes are not fully understood, but its flares and complications can be managed through lifestyle changes—such as avoiding sun exposure (using SPF >55), quitting smoking, managing stress, and maintaining a healthy diet. See Dai et al., (Sig Transduct Target Ther 10, 102 (2025). There is no known way to completely prevent rheumatoid arthritis (RA), you can lower your risk or delay its onset by quitting smoking, improving your dental hygiene, eating an anti-inflammatory diet rich in omega-3s, maintaining a healthy body weight, and staying physically active. There is no proven way to prevent alopecia areata because it is an autoimmune condition where the body mistakenly attacks its own hair follicles. While you cannot stop the condition from developing, you can manage potential triggers to help reduce flare-ups or stop existing spots from spreading. See National Alopecia Areata Foundation. There is no known way to prevent Behçet’s disease because its exact cause is currently unknown. It is not considered a contagious disease, so it cannot be caught from another person. Experts believe it is an autoimmune condition where the body's immune system mistakenly attacks its own healthy blood vessels, likely triggered by a combination of genetic predisposition and environmental factors. There is no known way to prevent myositis because it is a rare autoimmune disorder where the immune system mistakenly attacks healthy muscle tissue. However, if you already have the condition (such as polymyositis, which affects multiple muscles), you can prevent disease progression, minimize flare-ups, and avoid long-term muscle damage by actively managing the illness. See Cleveland Clinic. Chronic thyroiditis (most commonly Hashimoto's disease) is an autoimmune condition. While you cannot completely prevent it because genes play a big role, you can lower your risk or slow its progress. There was no treating of prevention or treatment.
Thus the state of art clearly shows there is no prevention of any condition selected from an immune-related disease in a subject in need thereof, the method comprising administering a helper T cell with an Lrig1 protein or a gene that encodes an Lrig1 protein to the subject as an active ingredient. There is no single treatment which prevents or treats any or all conditions selected from an immune-related disease in any type of subject in need thereof. These teachings collectively demonstrate that the prevents or treats of immune-related diseases is highly unpredictable.
(6) The amount of direction or guidance presented; (7) the presence or absence of working examples:
There is a lack of working examples in the specification for preventing or treating all types of immune-related diseases encompassed by the instant claims. Applicant has provided evidence of in vitro confirmation of the effector T cell inhibitory effect.
Additionally, the term "preventing" is generally understood in the art to encompass a total protection from disease or injury. Thus, given the high level of required effect, a high level of evidence showing prevention is also required. There are no examples directed to the palliative, preventative, or curative treatment of any immune-related diseases. Therefore, the instant specification does not provide evidence or substantial guidance commensurate in scope with the broadly claimed method in how to use the method to prevent or treat an immune-related disease in a subject, the method comprising administering a helper T cell with an Lrig1 protein or a gene that encodes an Lrig1 protein to the subject as an active ingredient. 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. Therefore, Applicants amendments are insufficient to overcome the scope of rejection because the arguments were not persuasive.
Response to Arguments
9. Applicant's arguments filed June 2, 2026 have been fully considered but they are not persuasive. Applicants failed to point to a single example of preventing or even treating any immune-related disease. At best, Applicants point to Kumar et al., teaching MS, RA, SLE, a significantly reduced ability to suppress Teff in the peripheral blood of patients. However, Kumar et al., do not teach the prevention of MS, RA or SLE. There was no evidence of prevention of MS, RA or SLE by administering a helper T cell with an Lrig1 protein or a gene that encodes an Lrig1 protein to the subject as an active ingredient.
Next, Applicants to Ha showing a well established that Cd4+CD25+ T reg cells have the capability to prevent autoimmune encephalomyelitis. Moreover, the “capability to prevent” is not equivalent to prevention. Preventing immune-related encephalomyelitis (and encephalitis) depends entirely on its underlying cause, as "primary" prevention is generally not possible because it is an unpredictable autoimmune response. However, you can effectively minimize your risk, manage secondary risk factors. See Autoimmune Encephalitis: What It Is, Symptoms & Treatment. Therefore, Applicants have not pointed to enablement of preventing autoimmune encephalitis and there is no prevention by administering a helper T cell with an Lrig1 protein or a gene that encodes an Lrig1 protein to the subject as an active ingredient.
Applicants urge that the claims narrowly focus on the prevention and treatment of all immune-related diseases in any type of subject. However, the claim focus is not viewed narrowly. For instance, many if not all of the immune-related diseases are not preventable. The instant specification at paragraph [0038] states “Prevention can be either complete or partial.” Therefore, complete prevention has not been described within the specification and Applicants have not pointed to any evidence that any prevention of any immune-related disease has been described.
Finally, Applicants have not pointed to any evidence to support the scope of enablement regarding method for the prevention of an immune-related disease in a subject, the method comprising administering a helper T cell with an Lrig1 protein or a gene that encodes an Lrig1 protein to the subject as an active ingredient.
New Grounds of Rejection Necessitated By Applicants Amendments
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
10. Claim 67 is 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.
It is noted that claim 67 fails to recite an administering the helper T cell with an Lrig1 protein being given to the subject. Therefore, it is suggested the claim recite the actual administration to the subject. Clarification is required to overcome the rejection.
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.
11. Claims 36, 39-40, 42 and 56-70 are rejected under 35 U.S.C. 103 as being unpatentable over KR20180116925 (published 2018-10-26) in view of Lee (US Pat Pub 20150239964 published 2015-08-27; priority to 2012-01-20)
The claims are drawn to a method for the prevention or treatment of an immune-related disease in a subject, the method comprising administering a therapeutically effective amount of a helper T cell with an Lrig1 protein or a gene that encodes an Lrig1 protein to the subject as an active ingredient.
KR20180116925 describe information in cell therapy for autoimmune disease prevention or treatment, including the Lrig-1 + immune cells of the present invention relates to the Lrig-1 + immune cells, immune diseases, prevention and treatment are described in the pharmaceutical compositions. KR20180116925 describe a cancer therapeutic agent for preventing or treating immune disease comprising Lrig-1 + immune cells. In the present invention, the cell therapeutic agent refers to a living cell used for cell therapy in which live cells are directly injected into a patient. Thus teaching claim 36. For the purpose of the present invention, the cell therapy agent may be a cell expressing Lrig-1 protein on the surface of T cell, more preferably the regulatory T cell may be CD4 + T cell, but is not limited thereto. Th0, Th1, Th2, Th17 and iTreg, which are subset of T cells, were prepared to confirm that Lrig-1 protein was expressed only in regulatory T cells (Tregs) [See examples 1 and 5]. Thus teaching claims 38 and 41. Figure 9 shows the Th1 and Th2 cells in combination with the Lrig1.
In the present invention, the above-mentioned immune diseases include Alopecia greata, ankylosing spondylitis, antiphospholipid syndrome, autoimmune adison disease, autoimmune diseases of the adrenal glands, autoimmune hemolytic anemia, autoimmune hepatitis, Autoimmune thrombocytopenia, Behcet's disease, vesicular pemphigoid, cardiomyopathy, celiac spruedermatitis, chronic fatigue syndrome, chronic inflammatory dehydration (demyelinating) polyneuropathy, Churg-Strauss syndrome, which are chronic inflammatory diseases. Thus teaching claim 39, 57, 61, 64, and 68-69. The present invention relates to a method of treating a patient suffering from Crohn's disease, rheumatoid polyposis, multiple myositis and dermatomyositis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, lupus erythematosus. Thus teaching claim 40. Thus, KR20180116925 describe the instantly rejected claims. Therefore, KR20180116925 teach the cell expressing Lrig-1 protein on the surface of T cell, can be Th0, Th1, Th2, Th17.
Lee teach a method for treating immune-related diseases comprising administering an effective amount of a protein comprising a cell membrane surface protein of Lrig1 protein, or a composition including all or part of the antibody specifically binding thereto to a subject with the immune-related diseases. The immune-related diseases may be any one selected from the group consisting of autoimmune diseases, graft versus host diseases, organ transplant rejection, asthma, atopy, acute and chronic inflammatory diseases, cardiovascular diseases and cognitive disorders [para 17].
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply KR20180116925’s Thelper (Th0, Th1, Th2 or Th17) expressed on the surface of Th0, Th1, Th2 or Th17 being administered to treat immune-related diseases comprising administering an effective amount of a protein comprising a cell membrane surface protein of Lrig1 protein, as taught by Lee, in order to treat autoimmune diseases, graft versus host diseases, or organ transplant rejection. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the method of treatment. Furthermore, no more than routine skill would have been required to incorporate the Thelper cell expressing Lrig-1 protein on its surface.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of treating a subject, comprising administering to the subject a therapeutically effective amount of an isolated monoclonal antibody which binds to and neutralizes flagellin, wherein the disease is well known and there is no change in the respective function of the Thelper cell expressing Lrig-1 protein on its surface or the immune-related diseases, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
12. Applicant’s arguments, filed June 2, 2026 with respect to the rejection(s) of claims 36-43 under KR20180116925 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Lee (US Pat Pub 20150239964).
Applicants argue that KR20180116925 do not anticipates the instantly claimed method because KR20180116925 is directed to regulatory T cells and not helper T cells; yet Applicants clearly acknowledge that KR20180116925 do teach helper T cells. Applicant is reminded that the MPEP section 2123 teaches that patents are relevant as prior art for all they contain, “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir.1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Therefore applicant’s argument is not persuasive especially when KR20180116925 teach the effector T cells of the present invention can be at least one of those selected from the group consisting of Th1, Th2, Th17 and Th22. The Th1, Th22, Th17 and Th22 are all T helper cells, just as claimed by the instant claims.
Therefore, the fact that Lrig-1 protein that is present specifically on the surface of regulatory T cells does not exclude administering Lrig-t protein and Th1, Th2, Th17 and Th22. KR20180116925 described cell therapy herein refers to a living cell used in a treatment method that is directly injected into the patient wherein the contents related to immune cells and Lrig1 protein are administered. Therefore KR20180116925 is not limited to only regulatory Tcells but also to the Thelper cells which KR20180116925 clearly describe.
Pertinent Art
13. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure. See WO2020190104 and KR20200112745. KR102306345, and 2020080853 all teach administering the LRIG1. See US Pat Pub 20150239964.
14. 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.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Peter Paras, can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/ Primary Examiner, Art Unit 1645
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