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 .
Response to Amendment
The amendment filed 1 July 2026 is acknowledged. Claims 6 and 7 are amended. New claims 10-11 are added. Claims 1-5 and 9, which were previously withdrawn as directed to an unelected invention, there being no allowable generic or linking claim, are cancelled.
Claim Status
Claims 6-8 and 10-11 are pending and under examination in the instant office action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Withdrawal of Objections
The objection to claim 6 for abbreviations without first writing out the long form is withdrawn in view of the amendments to the claims.
Withdrawal of Rejections
The rejection of claims 6-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the amendments to the claims.
The rejection of claim 7 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph for scope of enablement is withdrawn in view of the amendments to the claims.
The rejection of claims 6-7 under 35 U.S.C. 103 as being unpatentable over WO2019229247 to Altare et. al. published 5 December 2019 (Of record, IDS dated 5/4/2023) in view of Wang, Long, et al. "Graft-versus-host disease is enhanced by selective CD73 blockade in mice." PLoS One 8.3 (2013): e58397 (Of record, IDS dated 5/4/2023) is withdrawn in view of the amendments to the claims.
The rejection of Claim 8 under 35 U.S.C. 103 as being unpatentable over WO2019229247 to Altare et. al. published 5 December 2019 in view of Wang, Long, et al. "Graft-versus-host disease is enhanced by selective CD73 blockade in mice." PLoS One 8.3 (2013): e58397 (Of record, IDS dated 5/4/2023) as applied to claim 6 above and in further view of Goloshchapov, et. al. "Bacteroides fragilis is a potential marker of effective microbiota trans-plantation in acute graft-versus-host disease treatment. Cell Ther Transplant 2020; 9 (2): 47-59." cttjournal. com 48: 2 is withdrawn in view of the amendments to the claims.
The rejection of claims 6-7 on the ground of nonstatutory double patenting as being unpatentable over claims 1 of U.S. Patent No. 12405267 B2 in view of Godefroy E, et. al. Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases. Gastroenterology. 2018 Oct;155(4):1205-1217. doi: 10.1053/j.gastro.2018.06.078. Epub 2018 Jul 5. PMID: 29981781 and Wang, Long, et al. "Graft-versus-host disease is enhanced by selective CD73 blockade in mice." PLoS One 8.3 (2013): e58397 (Of record, IDS dated 5/4/2023) is withdrawn in view of approved terminal disclaimer between 18251809 and U.S. Patent No. 12405267 B2 filed 1 July 2026.
The rejection of claim 8 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12405267 B2 in view of Godefroy E, et. al. Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases. Gastroenterology. 2018 Oct;155(4):1205-1217. doi: 10.1053/j.gastro.2018.06.078. Epub 2018 Jul 5. PMID: 29981781 and Wang, Long, et al. "Graft-versus-host disease is enhanced by selective CD73 blockade in mice." PLoS One 8.3 (2013): e58397 (Of record, IDS dated 5/4/2023) as applied to claim 6 above and in further view of Goloshchapov, et. al. "Bacteroides fragilis is a potential marker of effective microbiota trans-plantation in acute graft-versus-host disease treatment. Cell Ther Transplant 2020; 9 (2): 47-59." cttjournal. com 48: 2 is withdrawn in view of approved terminal disclaimer between 18251809 and U.S. Patent No. 12405267 B2 filed 1 July 2026.
Claim Rejections - 35 USC § 112(b)- New, necessitated by amendment
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 6, 8 and 10-11 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.
Instant claim 6 recites a method for treating graft-versus host disease comprising “administering, to a subject having a level of CD73 expression by DP8α Tregs, a therapeutically effective amount of an immunosuppressive agent or an infusion DP8α Tregs exhibiting Faecalibacterium prausnitzii-derived DP8α” (emphasis is the Examiner’s). The claim defines DP8α Tregs as CD3+/CD4+/CD8αLOW/CCR6+/CXCR6+ cells, but does not define what F. prausnitzii-derived DP8α means. The instant specification describes F. prausnitzii DP8α target antigens (e.g. p. 15 lines 20-p. 16 line 11), but does not describe or define F. prausnitzii-derived DP8α means. The metes and bounds of the claim are unclear because it is uncertain 1) whether the phrase DP8α in the absence of “Treg” references only the biomarkers or cells comprising the biomarkers and 2) what features would be required of the biomarkers or the cells that would cause them to be F. prausnitzii-derived.
Dependent claims are rejected for failing to resolve the indefiniteness as described. Claim 7 is excluded because it narrows the method of treatment to the alternate administration of the immunosuppressive agent.
Claim Rejections - 35 USC § 112(a)- New Matter- New, necessitated by amendment
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.
Claims 6, 8, and 10-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claims 6 and 10 have been amended to recite the limitation “exhibiting Faecalibacterium prausnitzii-derived DP8α” (claim 6 line 13; claim 10 lines 2-3) which is not in the instant specification or the disclosures of PCT/EP2021/080557 or EP20306320.1 or any claim set. Although the specification describes exhibiting Faecalibacterium prausnitzii-derived DP8α target antigens (e.g. p. 15 line 20-p. 16 line 11), these limitation are not equivalent to each other. Therefore, the limitation is not supported in the disclosure.
Claim Rejections - 35 USC § 112(a)- Scope of Enablement- Modified, changes necessitated by amendment
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.
Claims 6, 8, and 10-11 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 graft-versus-host disease (GvHD) in a subject in need thereof comprising administering to a subject having a level of CD73 expression by DP8ɑ Tregs that is lower than a predetermined reference value a therapeutically effective amount of an immunosuppressive agent, wherein the immunosuppressant agent is a corticosteroid; particular immunosuppressive cytokines or cytokines that are immunosuppressive or immunosuppressive at particular doses such as IL-2 and IL-10 (see Jamil et. al. below); particular tyrosine kinase inhibitors (e.g. imatinib, see Jamil et. al. below. The examiner notes that an amendment to recite imatinib would result in new matter); particular monoclonal antibodies such as alemtuzumab, infliximab, vedolizumab, natalizumab, brentuximab vedotin, or rituximab (or particular monoclonal antibodies targeting antigens such as an anti-TNFalpha antibody as described in Jamil et. al., see below. The examiner notes that an amendment to recite anti-TNFalpha antibodies generically would result in new matter); or particular drugs acting to inhibit immunophilins such as cyclosporine, tacrolimus, sirolimus, or everolimus; and an infusion of DP8α Tregs.
does not reasonably provide enablement for the entire scope of the claimed method of GvHD comprising using:
Any other generic immunosuppressive agent;
Any infusion of DP8ɑ Tregs exhibiting F. prausnitzii-derived DP8ɑ
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the method of the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. In In re Wands, 8 USPQ2d 1400 (Fed. Cir., 1988) eight factors included for determining enablement:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The following is an analysis of these factors in relationship to this application.
Scope of the claims and nature of the invention
The instant claims are directed at a method of treating GVHD comprising administering a therapeutically effective amount of an immunosuppressive agent or an infusion of DP8α Tregs “exhibiting Faecalibacterium prausnitzii-derived DP8α” (See 112(b) rejection above). The instant specification states “As used herein, the term “Immunosuppressive agent” refers to a compound, composition or treatment that indirectly or directly enhances, stimulates, or increases the body’s immune response and/or that decreases the side effects of other therapies” (p. 16 lines 15-24). However, the examiner notes that this definition will not be considered limiting because “immunosuppressive agent” and “increases the body’s immune response” are contradictory and the instant specification cites glucocorticoids, which are known to decrease or suppress the body’s immune response (p. 16 line 21). Thus, the definition of “immunosuppressive agent” will be considered to be defined by the art understood definition, which would be any agent that slows or stops immune activation (See Cleveland Clinic, “Immunosuppressants: Definition, Uses & Side Effects. Accessed 26 March 2026. Web.). Regarding the administration of DP8α Tregs “exhibiting Faecalibacterium prausnitzii-derived DP8α”, the scope of exhibiting Faecalibacterium prausnitzii-derived DP8α is unclear and is not described by the specification.
Claim 7 limits the immunosuppressive agent to an immunosuppressive agents described, and is therefore excluded from this rejection.
Claim 8 limits to wherein the GvHD is acute GvHD. However, narrowing the scope of the disease does not narrow the scope of the immunosuppressive agent administered in the method of treating.
Claim 10 narrows the scope to the administration of DP8α Tregs “exhibiting Faecalibacterium prausnitzii-derived DP8α” (see enablement rejection below).
Claim 11 recites wherein the subject has received an allogeneic human stem cell transplant (allo-HSCT) but does not narrow the scope of the immunosuppressive agent or DP8α Tregs administered.
State of the Relevant Art; level of ordinary skill; and level of predictability in the art
Methods of treating both acute and chronic GVHD with many types of immunosuppressive agents are known in the art. For example, Jamil, Muhammad Omer, and Shin Mineishi. "State-of-the-art acute and chronic GVHD treatment." International journal of hematology 101.5 (2015): 452-466 (PTO-892 dated 4/6/2026) teaches that a combination of corticosteroid with a calcineurin inhibitor is the mainstay of initial management of acute and chronic GvHD (Introduction ¶1, “Treatment of acute GVHD” section ¶1). Jamil et. al. teaches that treatment of steroid-refractory acute GVHD has been tested for multiple agents but none of the existing treatment provided convincing evidences for long-term benefits and the outcome of steroid-refractory aGVHD remains poor with mortality as high as 80% (“Treatment of acute GVHD section” ¶5). Jamil et. al. teaches that the therapies that have been tried for steroid-refractory acute GVHD are antithymocyte globulin (ATG), alemtuzumab (a humanized monoclonal antibody to CD52), anti-IL-2 receptor antibodies, anti-TNFɑ agents such the monoclonal antibody infliximab, extracorporeal photopheresis, mycophenolate mofetil, sirolimus (mTor inhibitor), pentostatin, and mesochymal stem cells (“Treatment of acute GVHD” section p. 456-458). For chronic GVHD, Jamil et. al. teaches administration of corticosteroids and cyclosporine (p. 458 “Treatment of chronic GvHD” section ¶1). Jamil et. al. teaches second-line treatment for chronic GvHD includes rituximab, extracorporeal photophoresis and PUVA, imatinib (a tyrosine kinase inhibitor), mycophenolate mofetil, sirolimus, pentostatin, IL-2 (low-dose for Treg expansion), methotrexate, bortezomib (a proteasome inhibitor), and thalidomide (p. 458-461 ““Treatment of chronic GvHD” section”).
Despite the breadth of different immunosuppressive agents that have been tried to treat GvHD, the class of immunosuppressive agents is so broad that it would not be possible to determine any and all immunosuppressive agents that may provide a therapeutic effect for GvHD. For example, Virella, Gabriel, et al. "Immunosuppressive effects of fish oil in normal human volunteers: correlation with the in vitro effects of eicosapentanoic acid on human lymphocytes." Clinical Immunology and Immunopathology 61.2 (1991): 161-176 (PTO-892 dated 4/6/2026) teaches that fish oil is an immunosuppressant. Interestingly, a different study from Hashmi et. al. observed a decrease in CD4+CD25+FoxP3+ Tregs and an increase in acute GVHD symptoms after allogeneic bone marrow transplant in mice (Al Hashmi. “Omega-3 from Fish Oil Augments GVHD through the Enhancement of Chemotherapy Conditioning Regimen and Selective FoxP3 Depletion.” Bone marrow transplantation. 48.6 (2013) (PTO-892 dated 4/6/2026)). Additional known compounds that act as immunosuppressants are alcoholic beverages (Percival, S. S., and C. A. Sims. "Wine modifies the effects of alcohol on immune cells of mice." The Journal of nutrition 130.5 (2000): 1091-1094 (PTO-892 dated 4/6/2026)) and glutamine supplementation (Zhang, Li, et al. "Glutamine supplementation improves the activity and immunosuppressive action of induced regulatory T cells in vitro and in vivo." Transplant Immunology 84 (2024): 102044 (PTO-892 dated 4/6/2026)). Because the immunosuppressive agents is defined only by function with no structure, and there is no degree of immunosuppression required, the scope of what may fall under the instant claims as what constitutes administration of an immunosuppressive agent is vast. Further, it is not predictable based on the instant art what may act as an immunosuppressive agent and in what contexts it may be immunosuppressive. For example, IL-2 is also considered to be an immunostimulatory agent depending on the dose and is administered for the purposes of activating the immune system.
Regarding Tregs exhibiting F. prausnitzii-derived DP8ɑ target antigens in the form of peptide, proteins, or bacteria/probiotics, there are no regulatory T cells exhibiting bacterial target antigens that were found in the art. Additionally, there is no evidence of record wherein a probiotic is a F. prausnitzii-derived DP8ɑ target antigen, and there is no guidance for how this would be derived.
Summary of Species disclosed in the original specification; the amount of direction provided by the inventor, existence of working examples; and quantity of experimentation needed to make or use the invention based on the content of the disclosure
The instant specification does not have any working examples of administering a therapeutically effective amount of an immunosuppressive agent to a patient having a level of CD73 expression by DP8ɑ Tregs that is lower than a predetermined reference value. The instant specification teaches examination of DP8ɑ Tregs in a cohort of patients with hematological malignancies treated by allo-HSCT: “Each sample was analyzed by flow cytometry to determine DP8ɑ Treg frequency among total CD3+ T cells” (p. 27 lines 13-14). The specification shows that at 30 days post-transplant the % CD73 expression was associated with the presence or absence of GvHD (Fig. 1A). The specification teaches that a non-significant trend towards a decrease of DP8ɑ Tregs and % CD73 expression was observed before mobilization in donors (Fig. 1B). The inventors demonstrate that blockade of CD73 abolishes DP8ɑ Treg suppressive function and acute GVHD patients had donors exhibiting lower frequencies of CD73-expressing DP8ɑ Tregs (Fig. 3). There are no working examples of comparisons with a pre-determined level of CD73 and no working examples includes the patients are administered an immunosuppressive therapy. Regarding immunosuppressive agents, the specification contemplates interferons (p. 17 lines 12-19); interleukins IL-2 and IL-10 (p. 17 lines 20-22); colony stimulating factors G-CSF, GM-CSF, and erythropoietin (p. 17 lines 23-32); monoclonal antibodies alemtuzumab, infliximab, vedolizumab, natalizumab, brentuximab vedotin, or rituximab (p. 18 lines 4-9); glucocorticoids for example prednisone, methylprednisolone, dexamethasone, and hydrocortisone (p. 18 lines 10-13); drugs acting on immunophilines including cyclosporine, tacrolimus, sirolimus, or everolimus (p. 18 lines 14-17); cytostatics including “but are not limited to alkylating agents, antimetabolites, methotrexate (folic acid, purine analogs, pyrimidine analogues…), azathioprine and mercaptopurine, cytotoxic antibitotics (e.g; anthracyclines, mitomycin C, bleomycin, mithramycin, dactinomycine…)” (p. 18 line 30-p. 19 line 2); tyrosine kinase inhibitors including ruxolitinib or itacitinib (p. 19 lines 3-8). According to the specification, treatment refer to both prophylactic or preventative treatment as well as curative (p. 19 lines 9-13). All of these are prophetically recited and there is no record of evidence of treating GvHD with many of these compounds for example, of treating GvHD with the antibiotic bleomycin. It would therefore take a person of ordinary skill in the art an undue amount of experimentation to determine which agents under the genus of immunosuppressive could be successfully used to treat GvHD given the breath of the current genus of immunosuppressive agents and the state of the art.
DP8ɑ Tregs exhibiting F. prausnitzii-derived DP8ɑ, is indefinite as described in the 112(b) rejection above, and the specification does not provide guidance. Rather, the specification refers to administration of two distinct therapies: treatment with F. prausnitzii-derived target antigens in the form of peptides, proteins, or probiotics/bacteria (Specification p. 28 lines 33-p. 29 line 2) and, as a separate therapy, an infusion of DP8ɑ Tregs “exhibiting appropriate features” (p. 15 lines 21-25). There is no working embodiments of treating GvHD comprising administering DPɑ Tregs.
Conclusion
The Applicant does not have enablement for a method of treating GvHD comprising administering any generic immunosuppressive agent as claimed. It would take undue experimentation to determine which immunosuppressive agents or administering DP8ɑ Tregs exhibiting F. prausnitzii-derived DP8ɑ in the instantly claimed genus would treat GvHD consonant with the scope of the instant claims.
Response to Arguments
Applicants’ arguments dated 1 July 2026 have been fully considered but are not persuasive. Applicant argues that claim 7 is now amended to limit the immunosuppressive agent to one or more selected from the group suggested to be enabled (Remarks 7/1/2026 p. 4-5); this is sufficient to narrow the scope of claim 7, but does not resolve the scope of enablement issues for claim 6 and dependents as described in the modified rejection, necessitated by amendment above (e.g. the scope of claim 6 still includes the non-enabled immunosuppressive agents as described). In addition, Applicant argues that the amendment to claim 6 to cancel the limitation “target antigens in the form of peptide, proteins, or bacteria/probiotics” and that claims 6 and 10 now recite administering DP8ɑ Tregs exhibiting F. prausnitzii-derived DP8ɑ. This is not persuasive because, as described in the modified scope of enablement rejection above, the metes and bounds of this method of treatment are unclear and there are no examples of methods of administering “DP8ɑ Tregs exhibiting F. prausnitzii-derived DP8ɑ”; as described, it would therefore take undue experimentation to determine the scope of administering “DP8ɑ Tregs exhibiting F. prausnitzii-derived DP8ɑ”.
Claim Rejections - 35 USC § 103- Maintained/Modified, changes necessitated by amendment
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.
Claims 6-7 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Farhadfar, Nosha, et al. "Microbiota phylogenic analysis revealed decreased abundance of Faecalibacterium Prausnitzii, an anti-inflammatory commensal bacterium, in patients with chronic graft-versus-host disease." (2018): 2119-2119 (PTO-892 dated 4/6/2026); Sarrabayrouse, Guillaume, et al. "CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease." PLoS biology 12.4 (2014): e1001833. (PTO-892 dated 4/6/2026); Godefroy E, et. al. Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases. Gastroenterology. 2018 Oct;155(4):1205-1217. doi: 10.1053/j.gastro.2018.06.078. Epub 2018 Jul 5. PMID: 29981781 (PTO-892 dated 4/6/2026); Wang, Long, et al. "Graft-versus-host disease is enhanced by selective CD73 blockade in mice." PLoS One 8.3 (2013): e58397 (Of record, IDS dated 5/4/2023); and U.S. 20160361300 to Schwartz et. al published 15 December 2016 (PTO-892 dated 4/6/2026).
Claim interpretation: The instant claims are directed towards a method including i) determining the level of CD73 expression by DP8ɑ Tregs in a sample obtained from the subject and ii) comparing the level determined at step i) with a predetermine reference value. The examiner notes that determining the level of CD73 expression by DP8ɑ Tregs in a sample reads on two types of levels: 1) determining the degree of expression as in CD73 high versus CD73 medium, such as the MFI on flow cytometry or 2) determining the level as a binary positive or negative in each cell, so the level in the “DP8ɑ Tregs” is expressed as a % of cells, which can be considered as determining the level of CD73 in the population of DP8ɑ Tregs.
Farhadfar et. al. teaches that loss of gut microbiota (GM) diversity and a shift in GM composition after allogeneic hematopoietic stem cell transplant (alloHCT) is associated with increased treatment related mortality due to graft-vs-host disease (GVHD). Farhadfar et. al. teaches that when the GM of patients with long-term chronic GVHD were compared to patients without cGVHD, there was a significant reduction in alpha and beta diversity, and in particular in the bacteria F. prausnitzii, which is a well-known anti-inflammatory commensal bacterium which is linked to inflammatory diseases. Farhadfar et. al. teaches that the differences in IL10 and TNFɑ between groups were also nearing significance. Farhadfar et. al. teach “Future studies are needed to better understand the immunomodulatory effects and potential therapeutic role of F. prausnitzii and GM composition in cGVHD to develop targeted interventions to improve outcomes of alloHCT recipients”. See entire abstract, Figure C.
Sarrabayrouse et. al. teaches the discovery of a new CD4CD8αα lymphocytes population (DP8ɑ) that is deficient in patients with inflammatory bowel disease that has a skewed repertoire toward the recognition of F. prausnitzii, a major Clostridium species of the human gut microbiota which is decrease in patients with IBD (Abstract, p. 8 left column ¶ 2-right column ¶2). Sarrabayrouse teaches that the DP8ɑ cells exhibit a Treg phenotype and functions including the expression of typical FoxP3 Treg markers (CD25 and CTLA4, for example, see p. 2 right column ¶4) and had a Treg like cytokine profile including the expression of IL-10 (p. 3 left column ¶1). Also see Fig. 2. Sarrabayrouse et. al. teaches that the DP8ɑ cells exhibit the regulatory functions of Tregs and inhibit the maturation of dendritic cells and CD4 T cell proliferation (p. 3 left column ¶2-right column ¶1, Fig. 3). Sarrabayrouse et. al. teach that the DP8ɑ cells with regulatory function are found in peripheral blood in addition to being resident in the lamina propria of the colon (p. 7 left column bottom ¶-p. 8 left column ¶1). Sarrabayrouse et. al. teaches “Herein we demonstrated that DP8α T cells, present in the human colonic LP and blood, represent a novel subset of T cells lacking Foxp3 but sharing with Foxp3 Treg most other regulatory markers and in vitro regulatory functions, and with Tr1 Treg the capacity to secrete IL-10. We also showed that a great part of these cells specifically recognized F. prausnitzii, a Clostridium cluster IV bacterium, that is a major component of the indigenous gut microbiota frequently decreased in patients with IBD [25]. In addition, we showed that DP8α cells are decreased in the blood and colonic mucosa of patients with IBD compared with healthy individuals and the healthy colonic mucosa of patients with CC, respectively” (Discussion ¶1); “ in ileal Crohn disease, F reduction correlates with an increased risk of post-operative recurrence, suggesting that disruption of the F level is involved in the pathogenesis [2]. Importantly, the frequency of DP8α PBL and, among these, the frequency of the F-specific cells were decreased in patients with IBD compared with healthy donors. In addition, DP8α lymphocytes were less frequent in the inflamed colonic mucosa of patients with IBD compared with healthy colonic LP of patients with CC. These observations may support a role of DP8α Treg in the control of IBD […] The decreased frequency of DP8α PBL in patients with IBD together with the reported decrease of F in the faeces of these patients suggests that there is a connection between reduced levels of F and decreased F-specific regulatory activity, potentially resulting in increased inflammation” (Discussion ¶8-9); In addition, both Treg seem to use different suppressive mechanisms as Tr1 suppression strongly depends on IL-10 and TGF-β activity, while these molecules, respectively, had a limited and no contribution to the suppressive activity of DP8α Treg (Figure 3d). Nonetheless, IL-10, the main inducer of Tr1 [13],[14], might also contribute to DP8α Treg induction as F is strong inducer of IL-10 secretion by peripheral mononuclear cells [2]” (Discussion ¶11); “The physiological significance of circulating microbiota-reactive Treg will be important to address also in non-IBD contexts. In mice, increased resistance to experimental colitis and allergy models was observed in Clostridium-abundant animals. This suggests that the proportion of gut Clostridium may affect both colonic homeostasis and systemic immune responses and lead to conclude that Clostridium-induced Treg mediate these effects [9]” (Discussion ¶14, emphasis is the Examiner’s). Therefore, Sarrabayrouse et. al. suggest that 1) the DP8ɑ Tregs regulate systemic and gut-related inflammation and may be involved in microbiota-related regulation of the immune system; 2) the DP8ɑ Tregs may act as a stable biomarker in inflammation-related diseases; and 3) That there may be an IL-10 independent immunosuppressive mechanism driving the suppressive function of DP8ɑ Tregs.
Godefroy et. al. teaches that the DP8ɑ Tregs inhibit T-cell proliferation via CD39 activity and express CD39 at heightened levels compared to other T cell types. Godefroy et. al. teaches that both the percentage and level of expression of CD39 are noticeably increased in DP8ɑ cells expressing CCR6 and CXCR6 as compared with total DP8ɑ cells or total CD4+ cells (Fig. 5). Treatment with the CD39 inhibitor POM-1 resulted in a loss of the Treg immunosuppressive activity of the DP8ɑ cells (Fig. 6), suggesting that the main driver of regulatory T cell activity in DP8ɑ cells in via CD39-dependent ATP hydrolysis.
Farhadfar, Sarrabayrouse, and Godefroy et. al. make obvious that the DP8ɑ T-cell population that is specific for F. prausnitzii (in particular CD3+/CD4+/CD8αLOW/CCR6+/CXCR6+ DP8α Tregs as taught by Godefroy) would be expected to contribute to or correlate with occurrence of GVHD in allo-HSCT patients wherein, like in IBD, there is a decrease in F. prausnitzii and therefore a decrease in the activity of the F. prausnitzii-reactive T-regulatory cell immunosuppressive function. This would have a reasonable expectation of success because Sarrabayrouse teaches this Treg function of the DP8ɑ Tregs in several inflammatory diseases of the gut and a person of ordinary skill in the art would understand the gut involvement in GVHD from Farhadfar et. al.
Farhadfar et. al., Sarrabayrouse et. al., and Godefroy et. al. do not make obvious determining the level of CD73 on this particular DP8ɑ Treg cell population. This deficiency is resolved by Wang et. al.
Wang et. al. teaches that CD73, also known as ecto-5’-nucleotidase, sequentially phosphohydrolyzes adenine nucleotides, leading to adenosine generation in tandem with CD39 (Introduction p. 1 left column). Wang et. al. teaches that “The importance of CD39 and CD73 in the functional activity of Treg through the production of adenosine has been recently highlighted in transplantation […] We then considered Tregs as a possible CD73 expressing defense against GVHD. We established that donor CD73 KO Tregs were less able than WT Tregs to suppress GVHD development, suggesting that Treg CD73 helps mitigate GVHD immunopathology” (p. 7 left column- right column). Wang et. al. teaches that CD73 is required by donor CD4+CD25+ regulatory T cells in order to suppress the development of GvHD and that removal of CD25+ donor cells significantly increased development of GvHD (p. 2 right column). Wang et. al. demonstrates that CD73 KO Tregs were less able to inhibit IFNγ production in an MLR assay. Further, Wang et. al. shows that in vivo, mice given T cell depleted (TCD) bone marrow with or without equal numbers of sorted CD4+CD25+ Tregs demonstrated that mice with the CD73 KO Tregs were less able than WT to suppress GvHD caused by WT CD4+CD25- T cells (Fig. 3; p. 2 right column).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to determine the level of expression of CD73 on the new DP8ɑ Tregs that appear to have independent immunosuppressive function outside of IL-10 as taught by Sarrabayrouse et. al., wherein the mechanism is linked to adenosine production by CD39 as taught by Godefroy et. al., to benefit from the assessment of whether these DP8ɑ CCR6+/CXCR6+ Treg cells regulate the immune system via CD73 as well as CD39 as an IL-10-independent mechanism for immune regulation as Wang et. al. teaches the importance of CD73 and the link between CD73 and CD39 function in Tregs. This would have a reasonable expectation of success because Farhadfar et. al., Sarrabayrouse et. al., and Godefroy suggest that the immunosuppressive function of DP8ɑ contributes to GVHD via an IL-10 independent mechanism of CD39 regulation and an artisan would understand from Wang et. al. that CD73 and CD39 lie in the same cellular pathway in regulatory T cells and therefore would require a therapy for GvHD because of the reduced regulatory T cells function would be expected to contribute to GvHD.
Farhadfar et. al., Sarrabayrouse et. al., Godefroy et. al. and Wang et. al. do not explicitly teach administering an immunosuppressive agent to a subject having a level of CD73 expression that is lower than a predetermined reference value (claim 6); or wherein the immunosuppressive agent includes one or more of cytokines, monoclonal antibodies, non-cytokine adjuvants, corticoids, cytostatics, tyrosine kinase inhibitor, or drugs acting on immunophilins.
This is resolved by U.S. 20160361300 to Schwartz et. al. Schwartz et. al. teaches method of preventing or treating graft-vs-host disease (Abstract) wherein they investigate biomarkers that correlate with the onset of GVHD: “According to one aspect, the described invention provides a method of predicting and monitoring progression of GVHD in a patient with a tumor receiving a transplant comprising: (i) obtaining pre-transplant and post-transplant liquid samples from the patient; (ii) detecting from the pre-transplant and post-transplant whole blood samples biomarkers for GVHD, quantifying and comparing the amounts of biomarkers in the pre-transplant and post-transplant whole blood samples; (iii) predicting and correlating the degree of GVHD progression in the patient based on increased biomarker levels in the post-transplant liquid samples; and treating the patient with a therapeutically effective regimen to reduce the GVHD progression” [0078]. Schwartz et. al. teaches that the ratio of certain Treg and Teff subsets in the blood can be examined because the subsets are crucial for the onset of GVHD. Schwartz et. al. teaches that CD4+Foxp3+CD73+ Tregs are crucial but difficult to use as circulating markers. Schwartz et. al. suggest using a novel CD4+CD146+CCR5+ T cell population as a biomarker of intestinal graft versus host disease (See [283]). Schwartz et. al. teaches comparing the values of biomarkers between pre-transplant and post-transplant time points (reads on “pre-determined reference value”) Schwartz et. al. teaches treating GVHD with Rho kinase inhibitors such as telmisartan or related angiotensin receptor blockers to reduce the use of corticosteroids ([0018-0019], [0091]), which therefore teaches treatment with a combination of corticosteroids and telmisartan (reads on wherein the method includes administering a corticosteroid).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to combine the method of assessing CD73+ Tregs and comparing it to a predetermined reference value (such as a pre-transplant value from the same patient) and administering an immunosuppressive corticosteroid for GVHD treatment of Schwartz et. al. with the method of assessing CD73 on DP8ɑ T cells in a subject with GVHD after allo-HSCT as taught by Farhadfar et. al., Sarrabayrouse et. al., Godefroy et. al. and Wang et. al. above in order to benefit from the method of assessing Treg populations as a biomarker for GVHD and administering GVHD treatment as taught by Schwartz et. al. This would have a reasonable expectation of success because both Schwartz et. al. and modified Farhadfar et. al. in view of Sarrabayrouse, Godefroy. and Wang suggest monitoring CD73+ cells on Treg populations as a risk factor for GVHD and a person of ordinary skill in the art would have a reasonable expectation success of measuring a known biomarker of Treg activity on a new Treg population implicated in a related inflammatory disease (and, by the Farhadfar et. al., implicated by the decrease of F. prausniztii and administering the requisite amount of traditional GVHD immunosuppressant therapies).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Farhadfar, Nosha, et al. "Microbiota phylogenic analysis revealed decreased abundance of Faecalibacterium Prausnitzii, an anti-inflammatory commensal bacterium, in patients with chronic graft-versus-host disease." (2018): 2119-2119. (PTO-892 dated 4/6/2026); Sarrabayrouse, Guillaume, et al. "CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease." PLoS biology 12.4 (2014): e1001833. (PTO-892 dated 4/6/2026); Godefroy E, et. al. Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases. Gastroenterology. 2018 Oct;155(4):1205-1217. doi: 10.1053/j.gastro.2018.06.078. Epub 2018 Jul 5. PMID: 29981781 (PTO-892 dated 4/6/2026); Wang, Long, et al. "Graft-versus-host disease is enhanced by selective CD73 blockade in mice." PLoS One 8.3 (2013): e58397 (Of record, IDS dated 5/4/2023); and U.S. 20160361300 to Schwartz et. al published 15 December 2016 (PTO-892 dated 4/6/2026) as applied to claim 6 above, and further in view of Goloshchapov, et. al. "Bacteroides fragilis is a potential marker of effective microbiota trans-plantation in acute graft-versus-host disease treatment. Cell Ther Transplant 2020; 9 (2): 47-59." cttjournal. com 48: 2 (PTO-892 dated 4/6/2026).
The teachings of Farhadfar et. al., Sarrabayrouse et. al., Godefroy et. al., and Schwartz et. al. in regards to claim 6 are in the 103 rejection above.
Farhadfar et. al., Sarrabayrouse et. al., Godefroy et. al., and Schwartz et. al. do not teach wherein the GvHD is acute GvHD.
This is resolved by Goloshchapov et. al.
Goloshchapov et. al. teaches that severe intestinal affection after allo-HSCT is a useful clinical model for evaluation of gut microbiome shifts and its correction after fecal microbiota transplantation (FMT) (p. 48 left column ¶3). Goloshchapov et. al. teaches treatment of acute intestinal GvHD and FMT followed by analysis of the microbiota (p. 48 right column). Goloshchapov et. al. teaches that responders and non-responders to treatment had different time courses (p. 53 left column) and that patients with full clinical response after FMT or placebo had increased amount of major microbial groups including F. prausnitzii (p. 53 left column; Table 4; Fig. 1 and Fig. 2).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to perform the method for treating GvHD as taught by Farhadfar et. al., Sarrabayrouse et. al., Godefroy et. al., and Schwartz et. al. above to the acute GvHD patients with lower F. prausnitzii in non-responding patients as suggested by Goloshchapov et. al. in order to benefit from improving treatment for another subpopulation that appears to have a link between loss of F. prausnitzii, decrease in number or function of F. prausnitzii-specific T regulatory cells, and heightened immune reactivity in such as GvHD as taught by Farhadfar et. al., Sarrabayrouse et. al., Godefroy et. al., and Schwartz et. al. This would have a reasonable expectation of success because both Farhadfar et. al. and Goloshchapov et. al. suggest involvement of gut microbiota in GvHD and an artisan would have a reasonable chance of achieving similar results in chronic and acute GvHD; further Schwartz et. al. teaches the GvHD may be acute or chronic and a person of ordinary skill in the art would be able to determine the appropriate GvHD treatment based on approved therapies for acute and chronic GvHD.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Farhadfar, Nosha, et al. "Microbiota phylogenic analysis revealed decreased abundance of Faecalibacterium Prausnitzii, an anti-inflammatory commensal bacterium, in patients with chronic graft-versus-host disease." (2018): 2119-2119 (PTO-892 dated 4/6/2026); Sarrabayrouse, Guillaume, et al. "CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease." PLoS biology 12.4 (2014): e1001833 (PTO-892 dated 4/6/2026); Godefroy E, et. al. Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases. Gastroenterology. 2018 Oct;155(4):1205-1217. doi: 10.1053/j.gastro.2018.06.078. Epub 2018 Jul 5. PMID: 29981781 (PTO-892 dated 4/6/2026); Wang, Long, et al. "Graft-versus-host disease is enhanced by selective CD73 blockade in mice." PLoS One 8.3 (2013): e58397 (Of record, IDS dated 5/4/2023); and U.S. 20160361300 to Schwartz et. al published 15 December 2016 (PTO-892 dated 4/6/2026) as applied to claim 6 above, and in further view of Elias, Shlomo, and Alexander Y. Rudensky. "Therapeutic use of regulatory T cells for graft‐versus‐host disease." British journal of haematology 187.1 (2019): 25-38.
Claim interpretation: As described in the 112(b) and 112(a) rejections above, claim 10 recites administering “an infusion of DP8α Tregs exhibiting Faecalibacterium prausnitzii-derived DP8α”. The metes and bounds of this limitation are not clear and the limitation “exhibiting Faecalibacterium prausnitzii-derived DP8α” is not described in the specification. For the purposes of expedited prosecution, the claim will be interpreted to recite administering an infusion of DP8α Tregs having a phenotype of CD3+/CD4+/CD8αLOW/CCR6+/CXCR6+.
The teachings of Farhadfar, Sarrabayrouse, Godefroy, Wang, and Schwartz in regard to claim 6 are in the 103 rejection above and are incorporated herein.
Godefroy additionally teaches that future studies should include “the manipulation of [F prausnitzii–specific DP8α CCR6+ CXCR6+ Treg] subset, or of its F prausnitzii-derived antigen, as a potential therapeutic strategy to treat IBD patients” (Discussion p.
Schwartz additionally teaches that the method of treating GvHD may further include an injection of Tregs which protect the most vulnerable GVHD sites, such as the gut, in a localized manner, and specifically describes administering gut-homing α4β7 Tregs (e.g. [0022], [0025], [0096],
Farhadfar, Sarrabayrouse, Godefroy, Wang, and Schwartz do not explicitly teach the method further comprising administering to a subject having a level of CD73 expression by DP8α Tregs that is lower than a predetermined reference value, a therapeutically effective amount of an infusion of DP8α Tregs.
This deficiency is resolved by Elias et. al.
Elias et. al. teaches that regulatory T cells restrain immune responses and augmenting the activity of Treg can by employed for the treatment of inflammatory or autoimmune diseases and allogeneic conflicts associated with transplantation such as GvHD after HSCT (p. 25 left column). Elias et. al. teaches that therapeutic use of Treg cells for GVHD in preclinical models shows protection from GVHD (e.g. Table II, p. 27-28). Elias teaches that certain properties of Treg cells including homing molecules are important for effectiveness at treating GVHD (p. 29 left column-right column). Elias et. al. teaches that several clinical studies have examined the efficiency of Treg cell therapy for GvHD (Table III, p. 31-33) and that treatments have shown reduced incidence of GVHD, reduced incidence of grade 2-4 GVHD, and reduced relapse compared to historical controls (Table III, p. 31-33).
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to perform the method of detecting CD73 expression in DP8α Tregs and comparison to a predetermined reference value as taught by Farhadfar, Sarrabayrouse, Godefroy, Wang, and Schwartz above, and to further perform a method of administering Tregs in order to treat or reduce the instance of GVHD in allo-HSCT patients as taught by Elias using DP8α Tregs in order to benefit from providing a subpopulation of Tregs that is associated with a gut inflammatory disorder as taught by Godefroy and possesses import Treg functions and properties as taught by Godefroy and Sarrabayrouse, including homing of the Tregs to the gut as taught by Schwartz and Godefroy. This would have a reasonable expectation of success because a person of ordinary skill in the art would understand that different subpopulations of T cells may act as Tregs and Sarrabayrouse and Godefroy teach that the DP8α Tregs perform important immunosuppressive function in the gut via CD39 and suppression of T cell proliferation; therefore a person of ordinary skill in the art would expect that the DP8α Tregs have the biological mechanisms to decrease the inflammatory response and treat GVHD.
Response to Arguments
Applicants remarks dated 1 July 2026 have been fully considered but are not persuasive. The arguments regarding the 103 rejections over WO2019229247 to Altare in view of Wang and Goloshchapov (Remarks 7/1/2026 p. 5) are moot in view of the withdrawal of the rejections as described above. Altare, Wang, and Goloshchapov do not teach or suggest CD3+/CD4+/CD8αLOW/CCR6+/CXCR6+. Regarding the rejection under 35 U.S.C. 103 in view of Farhadfar, Sarrabayrouse, Godefroy, and Schwartz, Applicant first argues that Farhadfar teaches chronic GVHD rather than acute GVHD and fails to teach method of administering CD3+/CD4+/CD8αLOW/CCR6+/CXCR6+ DP8α Tregs. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., acute GVHD and method of administering CD3+/CD4+/CD8αLOW/CCR6+/CXCR6+ DP8α Tregs) are either not recited or not required in the rejected claim(s). Claim 6 recites GVHD in general, which is a limitation met by Farhadfar as described in the 103 rejection above; as described in the 112(b) and 112(a) rejections above, claim 6 does not recite method of administering CD3+/CD4+/CD8αLOW/CCR6+/CXCR6+ DP8α Tregs but rather administering “an immunosuppressive agent or an infusion of DP8α Tregs exhibiting Faecalibacterium prausnitizii-derived DP8α”. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant next argues that Wang teaches that donor CD73 KO CD4+CD25 Tregs had an impaired ability to mitigate GVHD and that recipient GVHD is more effective in limiting GVHD than donor CD73 which teaches away from the invention (Remarks p. 6). MPEP §2123 states that “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971)”. As described in the 103 rejection above, Wang et. al. teaches that CD73 expression is important in Tregs for suppressing GVHD in addition to donor expression as described in the Abstract as cited by Applicant. For example, as described above, Wang et. al. shows that in vivo, mice given T cell depleted (TCD) bone marrow with or without equal numbers of sorted CD4+CD25+ Tregs demonstrated that mice with the CD73 KO Tregs were less able than WT to suppress GvHD caused by WT CD4+CD25- T cells (Fig. 3; p. 2 right column); therefore, as described in the 103 above, Farhadfar, Sarrabayrouse, and Godefroy in view of Wang make obvious measuring CD73 in the newly described CD3+/CD4+/CD8αLOW/CCR6+/CXCR6+ DP8α Tregs in order to determine whether CD73 expression is a potential IL10-independent mechanism with a reasonable expectation of success because a person of ordinary skill in the art would understand that the CD73 expression of Wang may apply to other subtypes of Tregs.
Applicant additionally argues that Schwartz teaches away from the claimed invention because CD4+Foxp3+CD73+ Tregs are difficult to use and suggests the use of CD4+CD146+CCR5+ T cells as a biomarker of intestinal GVHD. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As described in the 103 rejection above, it would have been obvious, at the time of filing, for a person of ordinary skill in the art to substitute the novel DP8α Tregs of Sarrabayrouse and Godefroy as taught by modified Farhadfar above in the method of measuring a Treg biomarker followed by an immunosuppressive treatment for GVHD as taught by Schwartz. This would have a reasonable expectation of success because a person of ordinary skill in the art would have a reasonable expectation success of measuring a known biomarker of Treg activity on a new Treg population implicated in a related inflammatory disease (and, by the Farhadfar et. al., implicated by the decrease of F. prausniztii and administering the requisite amount of traditional GVHD immunosuppressant therapies). Additionally, MPEP §2123 states that “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971)” and therefore the preferred CD4+CD146+CCR5+ Treg embodiment as taught by Schwartz does not constitute a teaching away.
Regarding the rejection of claim 8, Applicant argues that the rejection is traversed as described for the combination of Farhadfar, Sarrayrouse, Godefroy, Wang, and Schwartz (Remarks 7/1/2026 p. 7). This is not persuasive for the reasons described above.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/KATHLEEN CUNNINGCHEN/ Examiner, Art Unit 1646
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
