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 .
Election/Restrictions
This action is in response to the papers filed on 07/20/2026. Claims 2-7, 11-14, and 17-20 are currently pending as per claims filed on 07/20/2026. Claims 2, 4, and 6-7 have been amended, claims 19-20 are newly added, and claims 1, 8-10, 15 and 16 have been cancelled and claims 2-3, 5, 11-14, 17-18 and 20 have been withdrawn from consideration as per claims filed on 07/20/2026.
Applicants’ election with traverse of Group III, which include claims 4, 6, 7 (as amended), and 19, drawn to a genetically modified oligodendrocyte progenitor cell, in the reply filed on 07/20/2026 is acknowledged.
The traversal is on the ground(s) that the technical features of Group III substantially overlap those of nonelected groups I and II because the vector of claim 2 and the genetically modified induced pluripotent stem cell of claims 3 and 5 are utilized in the method of amended claim 6. Applicant further asserts that amended claims 7, 13-14, 18, and newly presented claims 19-20 should be examined with Group III because these claims overlap substantially.
Applicants’ arguments have been fully considered. These arguments are persuasive in part.
Applicants’ argument concerning claim 2 is not found persuasive. Claim 2 is directed broadly to a vector comprising a construct encoding anti-inflammatory cytokines and/or chemokines, whereas amended claim 6 requires a specific process that includes vectors encoding IL-10, IL-27, IL-3, and CXCL11. Examination of the vector of claim 2 is not limited to the specific vector arrangement or process of elected group III and is capable of use in materially different genetic-modification processes.
Applicants’ argument concerning claims 3 and 5 is not found persuasive. Claims 3 and 5 is directed to a genetically modified iPSC and a method to obtain the iPSC, respectively, whereas elected claim 4 is directed to a genetically modified oligodendrocyte progenitor cell. These are distinct cell products and methods for obtaining such. Moreover, the cells of claim 3 are broader than those of claim 4.
Applicants’ argument concerning claims 13 and 18 is not found persuasive. These claims are directed to applications or uses associated with the genetically modified OPC and the recited cytokines/chemokines in preparing a drug for treating or prevention of multiple sclerosis, rather than the elected OPC itself and the method of producing OPC. The genetically modified OPC of claim 4 is not limited to preparation of a drug for treating or prevention of multiple sclerosis and may be employed in materially different processes.
Applicants’ argument concerning claim 14 is not found persuasive. Claim 14 is directed to an application of the induction differentiation agent according to claim 7. However, claim 7 has been amended to recite “A method according to claim 6…”. Therefore, claim 14 does not constitute a further limitation of the elected method and does read on the elected invention.
Applicants’ argument concerning claims 11-12 and 17 is not found persuasive. These claims encompass use of the vectors or genetically modified cells of Groups I-III in materially different preparations and therapeutic applications and do not require the particular elected OPC or the complete method of preparing the OPC recited in elected claims 4 and 6. Applicants’ arguments with respect to cancelled claims 8-10 and 15-16 are moot.
Applicants’ argument concerning claim 20 is not found persuasive. Claim 20 requires additional consideration formulation, excipients, suitability for administration, and associated composition that is not required for the elected claims. Moreover, the elected cell has utility other than incorporation into a pharmaceutical composition.
Applicants’ argument concerning amended claim 7 and 19 is found persuasive and these claims will be examined with the elected group III.
With respect to the election of species requirement, applicant has amended the elected claims so that they are limited to the elected four factor species. Therefore, the argument that the alternatives are patentably distinct is rendered moot. The amended claims will be examined as requiring all four species.
The requirement is still deemed proper and is therefore made FINAL.
Claims 2, 5, 11-14, 17-18, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected subject matter, there being no allowable generic or linking claim.
It is noted that Group II, which consists of claims 10-19, has been cancelled as per claims filed 08/10/2026.
Therefore, claims 4, 6-7, 19 are subject to examination to which the following grounds of rejection are applicable.
Priority
The instant application is a CON of PCT/CN2022/116751 filed on 09/02/2022, which claims foreign priority to CHINA 202111033274.7 filed on 09/03/2021.
A certified untranslated copy of the foreign patent application CHINA 202111033274.7, filed May 22, 2024, which is in is provided with the instant application.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Thus, the earliest possible priority for the instant application is 09/03/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/25/2024 was filed before the mailing date of the non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 4, 6-7, and 19 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.
Examiner notes that the claims are interpreted in light of the applicants’ election of the group IL-10, IL-27, IL-3, and CXCL11 as the cytokines/chemokines that the claimed cell will express.
Claim 4 recites “preferably, the genetically modified oligodendrocyte progenitor cell
overexpresses IL-10, IL-27, IL-3, and CXCL11.” at line 3. This claim is indefinite because it is unclear if the term “preferably” is intended to be recited in the alternative or as an addition to the non-optional item. Therefore, the metes and bounds cannot be determined by one having ordinary skill in the art. For the purposes of examination, the claim is interpreted as NOT requiring the “overexpresses IL-10, IL-27, IL-3, and CXCL11”.
Claims 6-7, and 19 are rejected as they ultimately depend on and inherit the deficiencies of claim 4.
Claim 6 recites multiple instances of “preferably” (for example at line 13), “more preferably” (example at line 15) and “most preferably” (example at line 22). This claim is indefinite because it is unclear if the term(s) “preferably”, “more preferably”, and “most preferably” are intended to be recited in the alternative or as an addition to the non-optional item. Therefore, the metes and bounds cannot be determined by one having ordinary skill in the art. For the purposes of examination, the claim is interpreted as NOT requiring the limitations that follow “preferably”, “more preferably”, and “most preferably” in step (A).
Claims 6-7 contain the trademark/trade name “GlutaMAX”, which is a registered trademark. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is only a name and NOT a replacement for the description of a specific composition.
Claim 6 recites “a basal medium added with a second stage induction differentiation agent” in lines step (B) (2), (3) and (4). Claim 6 step B (1) already requires “a basal medium”. It is unclear if the recited basal medium is the same or different. If there are different media, it is recommended to use, for example, a second basal medium relative to a first basal medium. Appropriate correction is requested. Claim 7 recites multiple instances of “preferably”. This claim is indefinite because it is unclear if the term “preferably” is intended to be recited in the alternative or as an addition to the non-optional item. Therefore, the metes and bounds cannot be determined by one having ordinary skill in the art. For the purposes of examination, the claim is interpreted as NOT requiring the limitations that follow “preferably”.
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.
Claim(s) 4 is rejected under 35 U.S.C. 103 as being unpatentable over Khoshakhlagh et al. (WO2019108894A1) in view of Zhu et al. (Zhu J et al., Front Immunol. 2018) and in view of Zohar et al. (Zohar, Yaniv et al., The Journal of clinical investigation, 2014) and in view of McAlpine et al. (McAlpine, C.S. et al., Nature, 2021).
Regarding Claim 4, Khoshakhlagh et al. teaches methods for producing oligodendrocyte progenitor cells (OPCs) (Abstract). Khoshakhlagh et al. teaches “In some embodiments, the methods further include introducing into pluripotent stem cells at least one engineered nucleic acid encoding IL-10 and/or IFNbeta. In some embodiments, the methods further include culturing the OPCs to produce oligodendrocytes.” (Pg. 3, Lines 1-4). Thus, Khoshakhlagh et al. teaches genetically modified OPC expressing IL-10 and further teaches co-expression of IL-10 and IFNbeta. These teachings establish that a therapeutic OPC can be engineered to express multiple cytokines (Pg. 32, Example 3).
Although Khoshakhlagh et al. teaches simultaneous expression of multiple cytokine genes in the cell of their invention they do not expressly teach that the OPC expresses IL-27, CXCL11, and IL-3.
Zhu et al. teaches Il-27 is an immunomodulatory cytokine having utility in autoimmune encephalomyelitis, animal model of multiple sclerosis (Abstract). Zhu et al. specifically teaches gene mediated expression of Il-27 using an AAV vector and demonstrates that IL-27 inhibits Th17 responses and inflammation (Results, Section: Systemic delivery of IL-27 by AAV Virus Inhibits TH17 Responses and Prevents EAE Development). Zhu et al. teaches “AAV-mediated delivery of IL-27 is highly efficient and results in stable and high concentrations in the blood of the treated mice” (Pg. 10, 1st Column, Final paragraph).
Zohar et al teaches CLCL11 as an immunoregulatory chemokine for suppressing inflammation and autoimmune encephalomyelitis (Abstract). Zohar et al teaches that CXCL11 signalling induces an “immunotolerizing” T-cell state character by IL-10 high regulatory - cells and that CXCL11 can redirect inflammatory T-cell polarization toward a regulatory phenotype (Pg. 2009, Final paragraph; Results, 1st Paragraph). Zohar characterizes CXCL11 as capable of inducing regulatory-Tcell production and prolonged disease suppression (Discussion, 2nd Column 1st full Paragraph; Figure 4E and 4F).
McAlpine et al. teaches IL-3 as an immunomodulatory cytokine with roles in inflammatory and autoimmune diseases (Pg. 701, 1st Paragraph). McAlpine et al. teaches that Il-3 regulates immune-response and motility programs in microglial cells (Figure 4.). McAlpine et al. demonstrates that direct cortical IL-3 produces rapid microglial mobilization, continuous intraventricular IL-3 reduces pathological burden and improved memory (Figure 5).
It would have been prima facie obvious to a person having ordinary skill in the art at the time of the instant application filing to modify the method of producing an OPC expressing multiple cytokines as taught by Khoshakhlagh et al., to further include expression of IL-27 (as taught by Zhu et al.), CXCL11 (as taught by Zohar et al.), and IL-3 (as taught by McAlpine et al.). One would have been motivated to combine these teachings to produce a genetically modified oligodendrocyte progenitor cell (OPC) capable of modulating/enhancing autoimmune inflammatory response. Zhu demonstrates Il-27 as a gene-deliverable immunomodulatory cytokine capable of suppressing auto immune response. Zohar teaches CXCL11 as an immunoregulatory signal capable of promoting regulatory immune response and suppressing autoimmune inflammation, and McAlpine demonstrates IL-3 can modulate microglial cells.
There would be a reasonable expectation of success in combining these teachings to produce an OPC engineered to express multiple cytokines as immunomodulatory factors as Khoshakhlagh et al. provides teachings that establish the production of genetically engineered OPCs that are capable of expressing multiple exogenous therapeutic cytokines. Moreover, using viral vectors to incorporate multiple genes was well understood in the art prior to the filing of the instant application.
Claim(s) 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Khoshakhlagh et al. (WO2019108894A1) in view of Zhu et al. (Zhu J et al., Front Immunol. 2018) and in view of Zohar et al. (Zohar, Yaniv et al., The Journal of clinical investigation, 2014) and in view of McAlpine et al. (McAlpine, C.S. et al., Nature, 2021) as applied to claim 4 above and further in view of Douvaras et al. (Douvaras P et al., Int J Mol Sci., 2016) and Herrera-Vaquero et al. (Herrera-Vaquero M. et al., Neuropathol Appl Neurobiol. Epub 2020).
Regarding Claims 6-7, The combined teachings of Khoshakhlagh, Zhu, Zohar, and McAlpine render obvious the cell of claim 4 as described in the 103 rejection above, the content of which is incorporated herein in its entirety. Moreover, Khoshakhlagh et al. teaches genetically modifying iPSCs into oligodendrocyte progenitor cells. Specifically, Khoshakhlagh et al. teaches co-electroporation of iPSCs with expression vectors encoding cytokines and inducing the engineered iPSCs to differentiate into cytokine-secreting OPCs (Pg. 32, Example 3). However, Khoshakhlagh, Zhu, Zohar, and McAlpine combined do not teach the four-stage culture differentiation protocol (and respective media + components) as recited in instant claim 6 or the requirement for the media to contain an NEAA in each induction step as recited in instant claim 7.
Herrera-Vaquero et al. teaches induction of iPSCs in DMEM/F-12 GlutaMAX medium containing beta mercaptoethanol, SB431542, LDN193189, retinoic acid, insulin, 1x NEAA (Pg. 269-270, NPCs generation and isolation). This reads on the first stage induction differentiation and medium.
Douvaras et al. teaches a sequential differentiation protocol for producing OPCs from human iPSCs. At day 8, cells are cultured in N2 medium comprising DMEM/F-12, NEAA, GlutaMAX, 2-mercaptoethanol, and N2 supplement with RA and SAG added to the medium (Pg. 11, Section 4.3). Douvaras et al. further teaches cells are then cultured in N2B27 medium comprising N2 medium together with B27 and insulin, in addition to RA and SAG (Pg. 11, Section 4.3). Douvaras et al. teaches the use of PDGF to drive oligodendrocyte commitment. This medium contains N2B27 medium, PDGF, IGF, HGF, NT-3, biotin, cAMP (Pg. 11, Section 4.3). The NEAA taught by Douvaras is carried through the second, third, and fourth differentiation media, as recited in the instant claim 7.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to apply a method allowing one to differentiate the genetically modified iPSCs from the combined teachings of Khoshakhlagh, Zhu, Zohar, and McAlpine using the iPSC to OPC differentiation conditions taught by Douvaras et al, combined with the neural-induction medium taught by Herrera-Vaquero et al., including use of NEAA as taught by both Douvaras and Herrera-Vaquero. One would have been motivated to combine these teachings with reasonable expectation of success because Douvaras et al. and Herrera-Vaquero et al. establish culture conditions shown to successfully direct human iPSCs through neural progenitor and oligodendroglial differentiation to obtain OPCs.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Khoshakhlagh et al. (WO2019108894A1) in view of Zhu et al. (Zhu J et al., Front Immunol. 2018) and in view of Zohar et al. (Zohar, Yaniv et al., The Journal of clinical investigation, 2014) and in view of McAlpine et al. (McAlpine, C.S. et al., Nature, 2021) as applied to claim 4 above and further in view of Douvaras et al. (Douvaras P et al., Int J Mol Sci., 2016) and Herrera-Vaquero et al. (Herrera-Vaquero M. et al., Neuropathol Appl Neurobiol. Epub 2020) as applied to claim 6 above and further in view of Szymczak-Workman et al. ( Szymczak-Workman AL et al., Cold Spring Harb Protoc., 2012)
Regarding Claim 19, The combined teachings of Khoshakhlagh, Zhu, Zohar, McAlpine, Douvaras, and Herrera-Vaquero render obvious the cell of claim 4 and method of producing the cell in claim 6 as described in the 103 rejections above, the content of which is incorporated herein in its entirety.
Moreover, Khoshakhlagh teaches that multiple cytokines cytokine-encoding sequences may be introduced into the same induced pluripotent stem cells using separate expression constructs (Example 3.) or constructs or alternatively multiple cytokine coding sequences within a common expression construct for simultaneous expression (Example 4).
However, they do not teach the exact vector architecture of claim 19, “wherein the vector is a combination of the following three vectors: a vector comprising the nucleotides encoding the anti-inflammatory cytokine IL-10 and the nucleotides encoding the anti-inflammatory cytokine IL-27, a vector comprising the nucleotides encoding the anti-inflammatory cytokine IL-3, and a vector comprising the nucleotides encoding the chemokine CXCL11.”
Szymczak-Workman et al. teaches that multicistronic vectors were a known means for delivery of multiple genes and allow for multiple protein coding sequences to be expressed from a single vector. Szymczak-Workman et al. teaches that 2A-linked multicistronic vectors used for multigene delivery can express multiple proteins from a single open reading frame and that inserting 2A sequences between genes permit efficient production of discrete proteins from a single vector, with nearly complete separation and substantially stoichiometric/concordant expression (Abstract). Szymczak-Workman also teaches practical vector design (Pg.201 all). Moreover, they teach that multicistronic vectors were used in biomedical research and gene therapy (Concluding remarks). Thus, Szymczak-Workman et al. teaches consolidation of multiple predetermined coding sequences onto a common vector was known and predictable multigene-expression strategy.
It would have been prima facie obvious to a person having ordinary skill in the art at the time of the instant application filing to modify the four-factor expression system within the combined teachings of Khoshakhlagh, Zhu, Zohar, McAlpine, Douvaras, and Herrera-Vaquero to consolidate two of the four sequences onto a common vector, while maintaining the remaining coding sequences on separate vectors, because Khoshakhlagh teaches the use of both separate and combined cytokine expression constructs and Szymczak-Workman et al. teaches consolidation of multiple protein coding sequences onto a single multicistronic vectors as a known and predictable technique for multigene expression. A person of ordinary skill in the art would have had a reasonable expectation that such an arrange would be successfully express the respective proteins.
Furthermore, selection of IL-10 and IL-27 as two coding sequences provided on a common vector would have amounted to selection from a finite number of predictable arrangements for distributing the four predetermined coding sequences among three vectors.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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