DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to an amendment filed 11/5/2025.
Claims 1, 2, 10, 26-28, 49-51, 67, 68, 71, 74 and 75 are pending.
This application is a 371 filing of PCT/AU2021/050254 filed 3/19/2021 which claims priority to Australian provisional application AU 2020900864 filed 3/20/2020.
Information Disclosure Statement
Information disclosure statements filed 12/8/2025, 11/12/2025 and 11/5/2025 have been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action. Initials indicate that the document has been considered even if the reference is lined through. A Genbank reference was not found in the file and has been crossed off.
Response to Amendments
The replacement drawings are sufficient to overcome the objections to the claims. The amendments are sufficient to overcome the rejection under 35 USC 101. Applicants amendments are sufficient to overcome in part the rejection under 35 USC 112, first. The rejection remains for claims 68 and 71.
Claim Objections
Claims 28, 49, 50 and 51 are objected to because of the following informalities: upon reconsideration, the article “the” is required prior to “TCRb chain “ in line 2 of claim 28. Each independent limitation requires their own article. This is a new observation.
Claim 49 has been amended to read on a first population of T regulatory cells that become a second population of T regulatory cells. Reference to “the T regulatory cells” in line7 of claim 49 obviously refers to the second population of cells. However, this should be properly indicated in the claim. This is true of claim 50. This objection is new necessitated by applicants’ amendment.
Claim 51 uses an abbreviation SmB/B’ which is not defined in the claims. For completeness the claim should include the full meaning. This is a new observation.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, 10, 26-28, 49, 50, 67, 68, 71, 74 and 75 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. These are new rejections necessitated by applicants’ amendment.
Claim 1 provides reference sequences comprising CDR sequences that are linked. For example, (A) (1) recites CDR1, 2, 3 for the Va domain is the amino acid sequences of SEQ ID NO:6, 7, 8. are obtained. The dependent claims are included in the rejection because they fail to address or clarify the basis of the rejection as discussed in detail for the independent claims.
However, they do not all conform to the SEQ ID NO: sequences for the comprised in TCRa chains in claim 26. For example (and this is found in most of the sequences), SEQ ID NO:501 contains SEQ ID NO:6 as underlined. It is the only TCRa chain to have this sequence. It also contains SEQ ID NO:7. But SEQ ID NO:8 is not in this sequence.
MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTI NCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSN KGFEATYRKETTSFHLEKGSVQVSDSAVYFCALSSYGNK LVFGAGTILRVKSYIQNPDPAVYQLRDSKSSDKSVCLF
Looking at the Sm-HLA-3 in claim 27, for example, SEQ ID NO:9 does not comprise SEQ ID NO:405 as it should.
MMKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRVSQSFFWYRQYSGKSPELIMSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVSGNQFYFGTGTSLTVIPNIQNPDPAVYQLRDTRB
Because the combinations in full are not found together and the Ta/Tb chains do not comprise the sequences as recited, the metes and bounds of the claims and dependent claims are unclear. A review of each of the sequences is required of applicant to ensure that the sequences are proper.
Claims 49 and 50 are unclear. The claims require the cell of claim 1as part of the population of T regulatory cells. But, the cell of claim 1 is not a T cell. Thereafter, the cell is not used as the cell of claim 1 has a nucleic acid already. Yet, claims 49 and 50 only require the nucleic acid of claim 1. This nucleic acid is within the cell of claim 1. It is not clear how one could reduce to practice the method of claims 49 and 50 using the cell of claim 1as recited.
Claim 74 recites the limitation "the T regulatory cells" in claim 50. There is insufficient antecedent basis for this limitation in the claim. There are multiple T regulatory cells and it is not clear which is to be stabilized.
Claim 74 recites the limitation "the population of T cells" in claim 51. There is insufficient antecedent basis for this limitation in the claim. There are multiple population of T cells and it is not clear which is referenced.
Claim Rejections - 35 USC § 112 ¶4 rejection
The following is a quotation of the fourth paragraph of 35 U.S.C. 112:
Subject to the [fifth paragraph of 35 U.S.C. 112 prohibiting improper multiple dependent claims], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 26 and 27 are rejected under 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 26 and 27 recite a number of TCRa and b chains comprising the elements of claim 1. However, the TCRa and b in claims 26 and 27 do not have the appropriate complementary sequences set forth in claim 1. For example, SEQ ID NO:501 contains SEQ ID NO:6 as underlined. It is the only TCRa chain to have this sequence. It also contains SEQ ID NO:7. But SEQ ID NO:8 is not in this sequence.
MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTI NCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSN KGFEATYRKETTSFHLEKGSVQVSDSAVYFCALSSYGNK LVFGAGTILRVKSYIQNPDPAVYQLRDSKSSDKSVCLF
Looking at the Sm-HLA-3 in claim 27, for example, SEQ ID NO:9 does not comprise SEQ ID NO:405 as it should.
MMKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRVSQSFFWYRQYSGKSPELIMSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVSGNQFYFGTGTSLTVIPNIQNPDPAVYQLRDTRB
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements
Claim Rejections - 35 USC § 112, first paragraph
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.
Claims 51 and 74 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a new rejection necessitated by applicants amendment.
Claim 51 recites that the peptide comprises an amino acid sequence of or an equivalent to residues 1-15 or 58-71. First, the recitation of “an amino acid sequence” means it can be one dipeptide from the list. As well, the term equivalent is used in the disclosure but is not described in a way that one would know that there is an equivalent sequence. The disclosure only teaches
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As to claim 74, the disclosure does not teach how one would stabilize the cells. There is only discussion on how to stabilize the patient by treatment.
To this end, the MPEP provides such guidance (emphasis added). If the application as filed does not disclose the complete structure (or acts of a process) of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Compare Fonar, 107 F.3d at 1549, 41 USPQ2d at 1805 (disclosure of software function adequate in that art).
Because the specification does not provide the requisite description of either equivalents or stabilization of T cells, one cannot envision the claimed invention.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 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 68 and 71 are rejected under 35 U.S.C. 112, first paragraph, because the specification is enabled for a method of treating systemic lupus erythematosus (SLE) who are antiSm and HLA-DR15 positive with autologous T cells that have been engineered to comprise TCR as defined in claim 1 and a binding protein to a complex of SmB/B’ and HLA-DR15 (defined as Smb/B’ 58-72), wherein the T cells , does not reasonably provide enablement for any other embodiment. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. This rejection is maintained for reasons of record but amended based upon applicants’ amendment and arguments.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of invention. The instant claims are drawn to immunotherapy or prevention of Lupus (an aberrant, unwanted or otherwise inappropriate response to a Smith protein) by use of T cells comprising a sequence encoding TCRs defined as a number of combinations of Va and Vb listed in claim 1.
2) Scope of the invention. The scope of the invention is broad in that claims 68 and 71 are drawn to any source of T cells to not only treat but also prevent lupus.
3) Number of working examples and guidance. Examples 3-4 detail epitope mapping as well as HLA typing of the Sm peptides, the Sm peptides were epitope mapped and HLA typed. The top three peptides were 1-15 and 58-72 of SmB/B’ and 43-57 of SmD3. The next step is said to be TCR transduction into Treg. However, the means of isolating the TCR are not provided for. The description teaches that the chains (a and b) are derived from a variety of alleles and provides method for isolating and purifying recombinantly produced soluble TCR (¶0212). Hence, as to the binding protein that is claimed, the description amounts to listing a number of TCR and potential means to modify them.
[0213] The SmB/B′-specific binding proteins or domains as described herein (e.g., SEQ ID NOS.:6-257, and variants thereof), may be functionally characterized according to any of a large number of art accepted methodologies for assaying T cell activity, including determination of T cell binding, activation or induction and also including determination of T cell responses that are antigen-specific.
4) State of the art. The art of antigen specific Treg cells requires generation of the binding peptides that are claimed as products and methods of use. At the time of filing, this method for therapeutic use was simply at pre-clinical evaluations for autoimmune disease. The art describes therapeutic potential (see Selck, abstract and Eggenhuizen, conclusion). The approach claimed follows that of Selck on page 4 as the cells are generated by introducing receptors into the cells. TCR are the mediators of the method. They recognize the target in an antigen specific manner and by so doing redirect T cell response against.
5) Unpredictability of the art. Claims 68 and 71 are drawn methods that treat or prevent Lupus associated with an aberrant, unwanted or otherwise inappropriate immune response to a Smith protein. As a first issue, the art of preventing autoimmune disorders is highly unpredictable. This requires predicting the subjects that would require treatment which would be highly unpredictable. In humans, the claimed diseases are usually established before therapy is offered. The specification does not adequately teach how to effectively predict for whom prevention would be required. One establishes a large genus of target subjects for whom the method is intended, however, establishing whether a person or persons actually requires the treatment is a highly unpredictable art. Screening procedures for indications of those requiring inhibition of the onset of disease are unknown and highly prejudicial leading to conditions in which those who require the treatment cannot be distinguished from those who do not. The physiological art is recognized as unpredictable. (MPEP 2164.03.) In cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved. In this case, applicants exacerbate the unpredictability of the art by reciting subjects to be targeted for whom the disease must be prevented.
The method as recited requires producing the T cells and administering the T cells to the subject. Complications using the methods clinically have hindered advancements of this approach,
Phase I and II clinical trials of polyclonal Tregs in T1D and other autoimmune diseases show that this therapy is safe and efficacious, and investigations into Treg therapy for other autoimmune diseases should be undertaken. Coupling the potent anti-inflammatory effects of Tregs with antigen specificity by transduction of a specific receptor offers much hope for future therapies to be even more specific and efficacious. The development and production of a successful Treg therapy continues to represent an exciting and challenging endeavor, which ultimately may improve autoimmune disease patient outcomes
Similarly, Selck on page 5, cautions projecting the translation of the pre-clinical results.
Several promising strategies to administer different kinds of antigenic drugs have been shown to inhibit inflammation and disease in preclinical models, but antigen delivery in human studies did not result in the same level of clinical improvements to date, with some of them even leading to worsening of disease (124) (reviewed in (125)). However, some reports detected signs of therapeutic benefit and induced immunotolerance which was associated with the expansion of FOXP3+ Treg cells (122, 123).
A first issue, is the characterization of the target. Applicants disclosure demonstrates identification of epitopes from Smith but no clear indication that this is the disease associated autoantigen. Selck teaches (page 6, col 1).
In order to develop efficient antigen-specific Treg cell-based treatments, disease-associated autoantigens must be well identified and characterized
Selck page 4.
Although these preclinical studies are encouraging, the translation of TCR-engineered Tregs into the clinic is somewhat limited by their major histocompatibility complex (MHC) restriction and the need to isolate and identify antigen-specific and disease-relevant TCRs.
Secondly, is the immature nature of the art where understanding of the clinical effects of the T cells are not known (Selck, page 6, col 1 and 7, col 2).
Importantly, uncertainties about the safety of Treg cell infusions and in vivo immunomodulatory interventions still remain and have to be investigated with caution. In particular, the in vivo maintenance and suppressive function of in vitro generated (polyclonal or antigen-specific) Treg populations is an essential factor for the toxicity and efficacy of adoptive cell therapies.
In order to develop safe and efficacious antigen-specific Treg therapies, further in-depth studies of the biology of human Treg cells during physiological homeostasis and autoimmune pathogenesis are needed. This requires new strategies to characterize distinct Treg subsets, better approaches to identify disease-relevant antigens and Treg defects as well as optimized tools to investigate clinical outcomes.
6) Amount of Experimentation Required. The invention recites use of a broad group of peptides by claiming them in terms of percent identity and combinations of sequences wherein functionally the disclosure and the claims have limited use purpose. These are used to produce Treg cells for therapeutic purposes and use of the peptides therapeutically for treatment and prevention. As set forth above the art of prevention is not possible especially with genetically disposed conditions. Furthermore, the claimed methods lack critical elements that make the methods possible such as guidance in the specification or a promoter or other expression control sequences. This allows nucleic acid sequences delivered to produce the proteins necessary for the intent of the invention. Finally, the art of treating autoimmune diseases with engineered Treg cells is a nascent art and the ability to use it thus in humans has not advanced such that as claimed it can be performed. Given the unpredictability of the art, the poorly developed state of the art with regard to predicting the structural/ functional characteristics of the TCR proteins, the lack of adequate working examples and the lack of guidance provided by applicants, the skilled artisan would have to have conducted undue, unpredictable experimentation to practice the claimed invention.
Response to Arguments
As regards the rejection of claims 68 and 71, applicants argue that the condition is limited to lupus. Applicants argue that data from Eggenhuizen et al 2024 provide correlative date to demonstrate efficacy. This reference could not be found in the file but was attained from the art and is attached. Applicants make note of figures 2B and 8. The scope has been edited based upon this reference. An earlier abstract demonstrates the reason for limiting the target, see Cheong et al, Abstract 2444.
Due to the strong association of LN with anti-Sm and HLA-DR15, we developed Sm-specific Tregs for potential treatment of LN.
It is noted that only post filing has use of allogeneic cells seen some success (see Yang et al, abstract and Discussion).
Double Patenting
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process ... may obtain a patent therefor ..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
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. See 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);and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1, 10, 27, 28, 49, 50, 67, 68, 71 and 75 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1, 2, 8, 9, 13-16, 20-23, 37, 38, 40, 44, 45, 47 and 48 of copending Application No. 18/693,109. This rejection is updated based upon applicants amendment.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in claims of the copending Application No. 18/693,109. That is, the cited claims of copending Application No. 18/693,109 anticipate and fall entirely within the scope of the rejected claims of the instant application. Specifically, both sets of claims are drawn to overlapping TCR and its use in methods of therapy for SLE.
The sequences claimed in the copending application SEQ ID NO:11-16 are found below.
(605)MMISLRVLLVILWLQLSWVWSQRKEVEQDPGPFNVPEGATVAFNCTYSNSASQSFFWYRQDCRKEPKLLMSVYSSGNEDGRFTAQLNRASQYISLLIRDSKLSDSATYLCVVPPGGGFKTIFGAGTRLFVKANIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAV AWSNKSDFACANAFTRB
(606)MGPQLLGYVVLCLLGAGPLEAQVTQNPRYLITVTGKKLTVTCSQNMNHEYMSWYRQDPGLGLRQIYYSMNVEVTDKGDVPEGYKVSRKEKRNFPLILESPSPNQTSLYFCASRTRTASYGYTFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQ PLKEQPALNDSRYCL
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the copending Application No. 18/693,109, then two different assignees would hold a patent to the claimed invention of copending Application No. 18/693,109, and thus improperly there would be possible harassment by multiple assignees.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
The combined CDR1,2, 3 for Va and Vb were not found in the art.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634