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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 2-23 in the reply filed on 6/26/2025 is acknowledged.
Claims 24 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/26/2025.
The instant application is a CON of 16/303,580, now U.S. Patent No. 11,702,630.
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.
Claims 2-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,702,630 in view of Lu et al. (2014, Neuron, Vol. 83, pgs. 789-796).
The instant claimed method requires the identical steps of producing CH10+ V2a interneurons as well as the same factors and concentrations in instant dependent claims 3-23 that are recited in claims 2-16 and 18-22 of ‘630. The difference between the instant claimed method however requires the transplantation of the produced CH10+ V2a interneurons into a non-human animal, however this would be obvious in view of the teachings of Lu et al. who teach transplanting human neuronal stem cells into rat spinal cords to model axonal growth (see Abstract and Introduction).
The instant application was filed as a CON and the court has found that safe harbor does not apply when the continuing application is filed as CON. The court found that safe harbor from an ODP rejection only applies when a continuing application is filed as a DIV. See AMGEN INC., v. F. HOFFMANN-LA ROCHE LTD. 580 F.3d l340; 2009 U.S. App, LEXIS 20409; 92 U.S.P.Q.2D (BNA) 1289.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 2-23 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 producing a mouse model of human V2a interneuron growth, comprising transplanting, into the spinal cord of a SCID mouse a population of cells comprising CH10+ V2a interneurons produced by culturing a population of human pluripotent stem cells (hPSCs) comprising,
a) culturing hPSCs in vitro in a neural induction medium comprising a retinoic acid signaling pathway activator, and
b) culturing the cells from a) in a neural induction medium comprising a retinoic acid signaling pathway activator, a sonic hedgehog (Shh) signaling pathway activator, and a Notch signaling pathway inhibitor,
so as to generate CH10+ V2a interneurons,
does not reasonably provide enablement for making a model in any species of non-human animal and transplanting into any region of the non-human animal. 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.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would have required undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experimentation to make or use the invention based on the content of the disclosure is ''undue'' (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). Furthermore, USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification, therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention, therefore skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
The claimed invention encompasses transplanting human CH10+ V2a interneurons into any non-human animal and into any region of a non-human animal to generate a model of human CH10+ V2a interneuron growth.
Whereas the nature of the invention is drawn to transplanting human CH10+ V2a interneurons into the spinal cords of SCID mice to study their growth, this teaching does not enable the claimed invention for its entire breadth.
Working Examples
The specification teaches in Example 6 the successful transplant of human CH10+ V2a interneurons into the spinal cords of C57/SCID mice, which resulted in integration of the human CH10+ V2a interneurons into host tissue, such that the transplanted interneurons survived, matured and extended to synapse into host cells of the mouse spinal cord.
However, while the claimed invention has successfully transplanted human CH10+ V2a interneurons into the spinal cords of SCID mice, the instant specification and the art doe not enable the claimed invention for its entire breadth.
Specifically, the claimed invention encompasses any non-human animal. This encompasses non-human animals such as a nematode, a mosquito, spiders and crustaceans such oysters and mussels. The skilled artisan would find at a minimum that the non-human animal would have to be a mammal to successfully model human interneuron growth. Particularly in view of dependent 3 and 4 which limit the site of transplantation to the spinal cord. Non-human animals such as oysters and mussels do not have spinal cords.
Further, even among non-human mammals the claimed invention is not fully enabled since the claims encompass the xenogenic transplant of human cells into a non-human mammal. In this regard, the art teaches that xenogenic transplant of human interneurons is not enabled in non-human mammals that have an immune system present.
Unpredictability of Cross-Species Transplantation
It should be emphasized that the specification only teaches practicing the claimed invention in SCID mice, which are an immunodeficient mouse model for receiving transplanted xenogeneic tissue. The specification does not teach or suggest any other species of immunodeficient animal other than SCID mice.
Regarding the unpredictability of cross-species transplantation or xenotransplantation the art teaches that using cross-species cells is unpredictable. For example, the art teaches that transplanting insulin-producing cells from non-human species into humans has met with limited success because of enhanced immune destruction of transplanted cells (Narang et al., 2006, Pharmacological Reviews, Vol. 58(2), pgs. 194-243, see pg. 196 col. 2 parag. 3). Narang continues to teach that the immune response towards xenogenic transplanted cells is mediated by both host's immune response through the generation of antigen presenting cells (APCs) towards the transplanted cells (pg. 200 col. 2 parag. 2 lines 1-8) via MHC II molecules and the cell surface expression of α-(1,3)-galactose moiety (pg. 200 col. 2 last 9 lines). Narang continues to teach that strategies to address host immune rejection of xenogenic transplanted cells have been developed (dendritic cell infusion, coactivation/costimulation blockade, T-cell inactivation etc), however their effectiveness as individual strategies is limited and requires finding the right combination of immune response modulation to increase the chances of transplanted cells surviving in the host (pg. 209 col. 2 parag. 2).
The art continues to teach that significants barrier to successful xenotransplantation. For example, Ekser et al. (Oct 21, 2011, The Lancet, pgs. 1-12) teach that while progress has been made regarding hyperacute rejection of xenotransplanted cells using an immunosuppressive regimen and the use of transgenic-modified pigs (pg. 3 col. 1 parag. 2) there still remains issues of unpredictability regarding xenotransplantation due to coagulation dysfunction and the T-cell proliferative response which are mediated via the hosts immune system despite immnosuppresive therapy in the host (pg. 7 col. 1 parag. 3 bridge col. 2).
Regarding the unpredictability of xenotransplantion of cells the art continues to teach that acute humoral xenograft rejection and coagulation dysregulation remain barriers to successful xenotransplantation. For example, Lin et al. (2009, Transplant Immunology, Vol. 21, pgs. 75-80) teach that while the barrier of hyperacute rejection of xenotransplanted cells from pig to primate has been largely overcome, acute humoral xenograft rejection remains a major hurdle for successful xenotransplantation (see Abstract parag. 1). Lin continues to teach that thrombotic microangtiopathy and systemic consumptive coagulopathy are increasingly recognized as barriers to successful xenotransplantation (see Abstract parag. 3 lines 1-2) and that a complex strategy of treatment may be required to understand and overcome these issues of unpredictability regarding the xenotransplantation of cells (see Table 1 and pg. 78 col. 1 parag. 4).
Site of Transplantation
The claims encompass modeling interneuron growth by transplanting human interneurons into any area of a non-human animal’s body. This thus would encompass the foot, kidney, heart, liver and pancreas of a non-human animal. However, the specification only teaches the spinal cord as the recipient transplant site for the transplanted human interneurons such that their growth can be “modeled” as claimed. While Applicant has successfully modeled the growth of human interneurons in host mouse spinal cord, the skilled artisan would find that transplanting human interneurons, particularly for the purpose of modeling their growth, in any site other than the spinal cord as unpredictable.
Conclusion
While Applicant has transplanted human CH10+ V2a interneurons into the spinal cords of SCID mice to study their growth, these teachings do not enable the claimed method for its entire breadth. The specification fails to teach or enable the claimed method any species of non-human animal other than SCID mice and transplanting human CH10+ V2a interneurons into any site other than the spinal cord. The art clearly teaches above that xenotransplantation is unpredictable due the innate cellular and antibody response in the recipient non-human animal to the transplanted cells.
Thus, the skilled artisan would require an undue amount of experimentation to make and use the invention as claimed without a predictable degree of success and thus limiting the claimed invention to the scope set forth above is proper.
Conclusion
No claims are allowed. The claims are free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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/DAVID A MONTANARI/Examiner, Art Unit 1632