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 .
Claims Status
The remarks filed 01/08/2026 are acknowledged.
Claims 1-28 are canceled.
Claims 29-49 are pending.
Applicant’s election without traverse of the following in the reply filed on 01/08/2026 is acknowledged: VH-VL for the order of the scFv and multiple sclerosis (MS) for the neurodegenerative disease. Upon further consideration, the election of species for the neurodegenerative disease (i.e. Species Group B) is withdrawn.
Claim 34 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/08/2026.
Therefore, claims 29-33 and 35-49 are under examination.
Priority
The instant application is a 371 of PCT/US2021/034968 and claims priority to provisional application 63/031,261. Priority is given with the earliest effective filing date of 05/28/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/18/2022 and 09/29/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Drawings
The drawings are objected to because:
(1) Figures 1-3, 6-9, and 13-25 do not meet the requirements of 37 CFR 1.84(a)(1) which requires that “India ink, or its equivalent that secures solid black lines, must be used for drawings.” The lines are pixelated and not solid.
(2) Figures 4-7, 9-12, and 15 comprise multiple panels. 37 CFR 1.84(u)(1) requires that partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 30 is objected to as being dependent upon a rejected base claim (i.e. claim
29), but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112(a)
Scope of Enablement
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 39-49 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 reducing inflammation in neural tissue of a subject comprising administering to the subject a plurality of engineered Tregs of instant claim 29, wherein the subject has a neurodegenerative disease selected from progressive supranuclear palsy (PSP), Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Multiple Sclerosis (MS), and chronic traumatic encephalopathy (CTE), does not reasonably provide enablement for a method of treating a neurodegenerative disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to 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 directed to a method for treating a neurodegenerative disease in a subject, the method comprising administering to the subject a plurality of engineered Tregs of claims 29-37, thereby treating the neurodegenerative disease. Claims 40-47 add the limitation of wherein the neurodegenerative disease is progressive supranuclear palsy (PSP), Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Multiple Sclerosis (MS), or chronic traumatic encephalopathy (CTE).
The claims are broad and inclusive of treating any neurodegenerative disease. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claims are directed. The instant specification does not provide any evidence that the administration of the engineered Tregs would treat any neurodegenerative disease, let alone those listed in instant claims 40-47. Applicant also does not provide an explicit definition of “treatment” and therefore, the art accepted definition of treatment encompasses care to prevent, cure, ameliorate, or slow progression of a medical condition [see Merriam-Webster; instant PTO-892]. There is no support provided in the instant specification or in the prior or instant art that teaches or supports the ability to prevent or cure any neurodegenerative disease encompassed by these broad claims.
Given the high level of required effect encompassed by “a method of treating a neurodegenerative disease” as instantly claimed, a high level of evidence showing treatment and/or prevention is also required. As noted above, however, there are no working examples in the instant specification demonstrating any therapy using the claimed treatment, nor any examples directed to the palliative, preventative, or curative treatment of any neurodegenerative disease. Therefore, the instant specification does not provide evidence or substantial guidance commensurate in scope with the broadly claimed method.
(F) The amount of direction provided by the inventor, (G) The existence of working examples:
There is a lack of working examples in the specification for treating any neurodegenerative disease encompassed by the instant claims. Applicant has not provided any substantive evidence of treating, preventing, or curing any neurodegenerative disease using the claimed method. There are no examples of administering the Tregs to any subject, and does not provide evidence that the engineered Tregs can treat any neurodegenerative disease.
(C) The state of the prior art, (E) The level of predictability in the art:
The field of prevention and treatment for neurodegenerative diseases is highly unpredictable. One such neurodegenerative disease encompassed by the instant claims is Alzheimer’s, and the cause of proteinopathies (i.e. Alzheimer’s) are still largely unknown today. For example, the Mayo Clinic, 2014 (instant PTO-892) states that scientists believe that for most people, Alzheimer's disease results from a combination of genetic, lifestyle and environmental factors that affect the brain over time. Less than 5 percent of the time, Alzheimer's is caused by specific genetic changes that virtually guarantee a person will develop the disease [page 1]. The National Institute of Neurological Disorders and Stroke (NINDS), 2015 (instant PTO-892) indicates that no treatments are available to slow progression of Alzheimer’s, although treatments do exist to help treat AD symptoms to improve quality of life [page 1, last paragraph – page 2, first paragraph]. Another example of an encompassed neurodegenerative disease is ALS, for which NINDS, 2013 (instant PTO-892) indicates that the cause is unknown and treatments are limited to a single drug that prolongs survival as well as treatments to manage the symptoms for palliative relief [page 4, last paragraph – page 7]. The story is much the same for frontotemporal dementia (FTD), another encompassed neurodegenerative disease, as described by D’Alton et al., 2014 (instant PTO-892). The current trialed therapy to date for FTD is based on management of symptoms and does not address cause, and the rationale for their use is based on efficacy in treating other neurodegenerative disorders or psychiatric conditions with similar behavioral phenotypes [page 1]. D’Alton suggests that there are still numerous challenges that must be met prior to effective therapeutic intervention to treat FTD [page 1].
Further, the specification does not provide substantive evidence that the claimed Tregs would be able to perform the functions set forth in the instant claims, with consideration given to the wide variety of encompassed neurodegenerative diseases. 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, 2004 (instant PTO-892), in vitro assays typically rely on simple interactions of chemicals with a drug target, but 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 [page 30, left column]. In addition, predicting the success of a treatment for neurodegenerative disease presents challenges beyond initial screening, because success rates for identifying therapeutics that can treat any central nervous system disease fall below the average for other diseases. Screening in animal models, such as mice, does not necessarily yield translatable results to other subjects such as humans, even if the mice duplicate some histopathological and biochemical features of a particular proteinopathy. Richardson et al., 2002 (instant PTO-892) teaches that transgenic designs emphasizing amyloid precursor protein produce mice that develop amyloid plaques, but did not form neurodegeneration [see Abstract] and that none of the mouse models recapitulate the complete neuropathology of AD [page 97, left column, fourth paragraph]. Gotz et al., 2018 (instant PTO-892) teaches that there is a lack of success in translating rodent data into therapeutic outcomes for AD [see Abstract]. Ittner et al., 2015 (instant PTO-892) indicates that the poor translational success of ALS and FTD models to date requires us to refine models and preclinical study design [see page 362]. To facilitate translation from mouse models to clinical trials and elucidate underlying disease mechanisms, it may become important to rethink our expectation that a ‘good’ mouse model of disease exactly reflects the symptoms seen in patients. This conceptualization has and will continue to fail us, given that mice and humans would probably present different overt phenotypes even if the underlying mechanisms were identical. For example, motor deficits are a prominent feature of tau transgenic FTD mouse models, yet only a fraction (<15%) of patients with FTD present with motor symptoms. Thus, Ittner suggests that functional changes in genetic mouse models be regarded as surrogate readouts for understanding novel pathomechanisms in a complex mammalian system, rather than as exact replicas of disease [see pages 363-364].
For the skilled artisan to practice the claimed invention, a demonstration of therapeutic or preventative effect of the engineered Tregs, in a subject and/or an in vivo model known to translate to treating humans or other encompassed subjects is required. Without this demonstration, the skilled artisan would not be able to reasonably predict the outcome of the claimed method, largely due to the lack of reliable animal models for neurodegenerative disease.
In conclusion, the claimed invention does not provide enablement for treating any neurodegenerative disease encompassed by the instant claims. Thus for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, and 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.
Claims 40-49, which depend from claim 39, are therefore rejected for the same reasons set forth above.
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.
Claims 29, 31-33, 35-45, and 47-49 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ashton-Rickardt (WO2019190879; 11/18/2022 IDS).
Regarding claims 29, 31, 32, and 38, Ashton-Rickardt teaches CAR-Treg cells that are CD4+CD127lo/-CD25+FOXP3+ [page 19, lines 15-31 – page 20, lines 1-6], a composition that comprises a plurality of engineered regulatory T cells (Tregs) in a therapeutically effective amount to treat a neurodegenerative disease that is not multiple sclerosis, each of the plurality of engineered Tregs expressing a chimeric antigen receptor (CAR) that specifically binds to a glial cell marker [claim 9], an engineered protein comprising a glial cell-specific binding protein coupled to a molecule expressed by a regulatory T cell (Treg) [claim 16], wherein the glial cell-specific binding protein is a tetrameric single-chain variable fragment (scFv) of an antibody molecule [claim 19], that the glial cell-specific binding protein binds myelin oligodendrocyte glycoprotein (MOG) [claim 21], and wherein the glial cell-specific of an antibody molecule comprising an amino acid sequence selected from the group consisting of SEQ ID NOs. 4, 6, and 12.
SEQ ID NO: 6 of Ashton-Rickardt comprises a VH region and a VL region with 100% sequence identity to SEQ ID NO: 6 of the instant application.
Regarding claim 33, since Ashton-Rickardt teaches an engineered Treg comprising a CAR with the same sequence as instantly claimed, then the CAR would necessarily be capable of directing the engineered Treg to a glial target cell that expresses MOG since function flows from structure. See MPEP 2112.01(II).
Regarding claim 35 of the instant application, SEQ ID NO: 6 of Ashton-Rickardt comprises, from N-terminus to C-terminus, VH region-VL region.
Regarding claims 36 and 37, residues 117-131 of SEQ ID NO: 6 of Ashton-Rickardt are a (GGGGS)3 linker.
Regarding claim 39, Ashton-Rickardt teaches a method for treating a neurodegenerative disease in a subject, the method comprising administering to said subject a therapeutically effective amount of regulatory T cells (Tregs), each expressing a chimeric antigen receptor (CAR) that specifically binds to a glial cell marker in order to protect neural tissue and reduce inflammation in the neural tissue, thereby treating the neurodegenerative disease, with the proviso that the neurodegenerative disease is not multiple sclerosis [page 2, lines 30-31 – page 3, lines 1-4, claim 1].
Regarding claims 40-45 and 47, Ashton-Rickardt teaches that the neurodegenerative disease to be treated may be progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease, Parkinson's disease (PD),
amyotrophic lateral sclerosis (ALS), chronic traumatic encephalopathy (CTE), or a prion disease [page 3, lines 10-15, claims 5 and 6-8].
Regarding claim 48, Ashton-Rickardt teaches that the CAR-Treg protects neural tissue and reduced inflammation in the neural tissue [page 3, lines 2-4].
Regarding claim 49, Ashton-Rickardt teaches that the subject is human [page 3, line 4; claim 2].
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 29, 31-33, and 35-49 are rejected under 35 U.S.C. 103 as being unpatentable over Ashton-Rickardt (WO2019190879; 11/18/2022 IDS), as applied to claims 29, 31-33, 35-45, and 47-49 above, in view of Fransson et al., 2012 (instant PTO-892).
The teachings of Ashton-Rickardt are above.
However, Ashton-Rickardt does not teach treating multiple sclerosis (MS) with the engineered Tregs that bind to MOG.
Regarding claim 46, Fransson teaches that Treg cell therapy has proved to be beneficial in the MS mouse model, and teaches that engineered Tregs expressing a CAR targeting MOG demonstrated suppressive capacity, reduced disease symptoms in the MS mouse models, and demonstrated sustained effects.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the engineered Tregs that bind to MOG of Ashton-Rickardt, to treat the subject with multiple sclerosis of Fransson. One would have been motivated to treat the subject of Fransson with the engineered Tregs that bind to MOG of Ashton-Rickardt with a reasonable expectation of success because Fransson teaches that Treg cell therapy has proved to be beneficial in the MS mouse model, and teaches that engineered Tregs expressing a CAR targeting MOG demonstrated suppressive capacity, reduced disease symptoms in the MS mouse models, and demonstrated sustained effects.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
U.S. Patent No. 12,173,030 (‘030)
Claims 29, 31-33, 35-45, and 47-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-10 of U.S. Patent No. 12,173,030 (‘030). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 29 and 38 of the instant application, claim 6 of ‘030 teaches a composition comprising a plurality of engineered regulatory T cells (Tregs), wherein the engineered Tregs of the plurality of engineered Tregs are CD4+CD127-CD25+FOXP3+cells wherein each engineered Treg of the plurality of engineered Tregs expresses a chimeric antigen receptor (CAR) that specifically binds to a glial cell marker wherein the CAR comprises a single-chain variable fragment (scFv) comprising the 6 CDRs present within SEQ ID NO:6, wherein the 6 CDRs are Kabat-defined CDRs, claim 7 of ‘030 teaches the composition of claim 6, wherein the 6 CDRs are (a)-(f), and claim 8 of ‘030 teaches the composition of claim 7, wherein the scFv has at least 99% sequence identity to SEQ ID NO: 6.
SEQ ID NO: 6 of ‘030 comprises a VH region and a VL region with 100% sequence identity to SEQ ID NO: 6 of the instant application.
Regarding claims 31 and 32 of the instant application, claim 9 of ‘030 teaches that the scFv is capable of specifically binding to the glial cell marker myelin oligodendrocyte glycoprotein (MOG).
Regarding claim 33 of the instant application, claim 10 of ‘030 teaches that the CAR is capable of directing the engineered Tregs to a glial target cell that expresses MOG.
Regarding claim 35 of the instant application, SEQ ID NO: 6 of ‘030 comprises, from N-terminus to C-terminus, VH region-VL region.
Regarding claims 36 and 37, residues 117-131 of SEQ ID NO: 6 of ‘030 are a (GGGGS)3 linker.
Regarding claims 39-45, 47, and 49, ‘030 teaches methods of treating a neurodegenerative disease in a subject comprising administering the Treg cells (i.e. plurality) expressing a CAR [column 2, lines 35-41], that the neurodegenerative disease may be progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), chronic traumatic encephalopathy (CTE), or a prion disease [column 2, lines 53-57], and that the subject may be human [column 2, lines 43-44].
See the decisions in Sun Pharmaceuticals v Eli Lily Fed Cir July 28, 2010; Geneva v GlaxoSmithKline 349, F.3d 1373; and Pfizer v Teva 518 F3d 1353 supporting the Office' s use of disclosed utilities of compositions when applying double patenting rejections to method claims.
Regarding claim 48, this claim merely recites effects or results of administering the engineered Tregs. Since ‘030 teaches administering the same Tregs as claimed to treat a neurodegenerative disease, a person of ordinary skill in the art would have reasonably expected these effects to occur, absent evidence to the contrary.
Claims 29, 31-33, and 35-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-10 of U.S. Patent No. 12,173,030 (‘030), as applied to claims 29, 31-33, 35-45, and 47-49 above, and further in view of Fransson et al., 2012 (instant PTO-892).
The teachings of ‘030 are above.
However, ‘030 does not teach treating multiple sclerosis (MS) with the engineered Tregs that bind to MOG.
Regarding claim 46, Fransson teaches that Treg cell therapy has proved to be beneficial in the MS mouse model, and teaches that engineered Tregs expressing a CAR targeting MOG demonstrated suppressive capacity, reduced disease symptoms in the MS mouse models, and demonstrated sustained effects.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the engineered Tregs that bind to MOG of ‘030, to treat the subject with multiple sclerosis of Fransson. One would have been motivated to treat the subject of Fransson with the engineered Tregs that bind to MOG of ‘030 with a reasonable expectation of success because Fransson teaches that Treg cell therapy has proved to be beneficial in the MS mouse model, and teaches that engineered Tregs expressing a CAR targeting MOG demonstrated suppressive capacity, reduced disease symptoms in the MS mouse models, and demonstrated sustained effects.
Copending Application No. 18/934,745 (‘745)
Claims 29, 31-33, 35-45, and 47-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-37, 40-43, and 47 of copending Application No. 18/934,745 (‘745; reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 29, 38, and 39 of the instant application, claim 30 of ‘745 teaches a method for treating a neurodegenerative disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of engineered regulatory T cells (Tregs), wherein the engineered Tregs are CD4+CD127-CD25+FOXP3+ cells that express a chimeric antigen receptor (CAR) that specifically binds to a glial cell marker, wherein the CAR comprises a single-chain variable fragment (scFv) comprising the 6 CDRs present within SEQ ID NO:12 or SEQ ID NO:6, wherein the 6 CDRs are Kabat defined CDRs, claim 40 of ‘745 teaches the method of claim 30, wherein the 6 CDRs are (a)-(f); and wherein the engineered Tregs are in a pharmaceutically acceptable carrier, and claim 41 of ‘745 teaches the method of claim 40, wherein the scFv has at least 99% sequence identity to SEQ ID NO: 6.
SEQ ID NO: 6 of ‘745 comprises a VH region and a VL region with 100% sequence identity to SEQ ID NO: 6 of the instant application.
Regarding claims 31 and 32 of the instant application, claim 42 of ‘745 teaches that the scFv is capable of specifically binding to the glial cell marker myelin oligodendrocyte glycoprotein (MOG).
Regarding claim 33 of the instant application, claim 43 of ‘745 teaches that the CAR is capable of directing the engineered Tregs to a glial target cell that expresses MOG.
Regarding claim 35 of the instant application, SEQ ID NO: 6 of ‘745 comprises, from N-terminus to C-terminus, VH region-VL region.
Regarding claims 36 and 37, residues 117-131 of SEQ ID NO: 6 of ‘745 are a (GGGGS)3 linker.
Regarding claims 40-45 and 47, claims 31-37 of ‘745 teach that the neurodegenerative disease is progressive supranuclear palsy (PSP), Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), or chronic traumatic encephalopathy (CTE).
Regarding claim 48, claim 47 of ‘745 teaches the method of claim 30, wherein the engineered Tregs reduce inflammation in neural tissue of the subject.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29, 31-33, and 35-49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-37, 40-43, and 47 of copending Application No. 18/934,745 (‘745; reference application), as applied to claims 29, 31-33, 35-45, and 47-48 above, in view of Fransson et al., 2012 (instant PTO-892).
The teachings of ‘745 are above.
However, ‘745 does not teach treating multiple sclerosis (MS) with the engineered Tregs that bind to MOG.
Regarding claims 46 and 49, Fransson teaches that Treg cell therapy has proved to be beneficial in the MS mouse model, and teaches that engineered Tregs expressing a CAR targeting MOG demonstrated suppressive capacity, reduced disease symptoms in the MS mouse models, and demonstrated sustained effects. Fransson also teaches that the engineered Tregs could be administered to humans without compromising the patients safety or the number of cells reaching its target.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the engineered Tregs that bind to MOG of ‘745, to treat the subject with multiple sclerosis of Fransson. One would have been motivated to treat the subject of Fransson with the engineered Tregs that bind to MOG of ‘745 with a reasonable expectation of success because Fransson teaches that Treg cell therapy has proved to be beneficial in the MS mouse model, and teaches that engineered Tregs expressing a CAR targeting MOG demonstrated suppressive capacity, reduced disease symptoms in the MS mouse models, and demonstrated sustained effects. It further would have been obvious to have treated a human subject with the engineered Tregs of ‘745. One would have been motivated to have administered the engineered Tregs of ‘745 to a human subject because Fransson teaches that the engineered Tregs could be administered to humans without compromising the patients safety or the number of cells reaching its target.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
The prior art does not teach a polynucleotide sequence comprising SEQ ID NO: 38 that encodes the CAR comprising a scFv that comprises a VH and VL region from SEQ ID NO: 6, as required by instant claim 30.
Conclusion
No claims are allowed.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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