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 .
Claims 1-8, 10-15, 20, and 22-26 have been amended and are under consideration.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), 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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 25 is rejected and claims 10-14 remain rejected under 35 U.S.C. 112(d) or pre-AIA 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.
(A)Claim 10 states that the reprogrammed Treg cell of claim 1 expresses higher levels of an immunosuppressive cytokine compared to a polyclonal Treg cell, and claim 11 specifies that that the immunosuppressive cytokine is Il-10 and/or TGF-beta.. The specification states that the inventive Tregs secrete higher levels of Il-10 and TGF-beta than that of polyclonal Tregs (pagev3, paragraph [0020]). Thus, the property of producing a higher level of immunosuppressive cytokine, specifically Il-10 and TGF-beta is an inherent property of the claimed Tregs, and fails to further limit claim 1. Claim 12 states that the reprogrammed Treg cell of claim 1 expresses lower levels of a proinflammatory cytokine compared to a polyclonal Treg. Claim 13 specifies that the proinflammatory cytokine of claim 12 is INF-γ, TNF-α,, Il-4 and/or Il-6. The specification states that the reprogrammed Treg cells express lower levels of proinflammatory cytokine compared to a polyclonal Treg and that the proinflammatory cytokines are specifically INF-γ , TNF-α,, Il-4 and/or Il-6 (page 60, paragraph [0170]). Thus, the property of producing lower levels of proinflammatory cytokines, and specifically INF-γ , TNF-α,, Il-4 and/or Il-6 is an inherent property of the claimed Tregs, and fails to further limit claim 1. Claim 14 states that the reprogrammed Treg cell of claim 1 increases suppression of CD4+ and CD8+ T cell proliferation compared to a polyclonal Treg cell. The specification states that the preprogrammed Treg cell increases suppression of CD4+ and CD8+ T cell proliferation compared to a polyclonal Treg (page 60, paragraph [0171]). All of the functional attributes of claims 10-14 are inherent in the inventive reprogrammed Treg cell, therefore claims 10, 12 and 14 fail to further limit claim 1 and claims 11 and 13 fail to further limit claims 10 and 12, respectively.
(B) Claim 25 states that the islet EV used in the method of making the reprogrammed Treg cell of claim 15 express autoantigens. Claim 15 requires that the islet EV comprise autoantigens. Thus, claim 25 fails to further limit claim 15.
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.
Applicant argues that the functional traits clamed in claims 10-14 are not inherent to the method, but by defining the specific inputs in the method steps the dependent claims re the result of a specific transformation result, not an “automatic” property of any generic Treg education. Applicant further argues that if high Il-10 secretion were inherent to Treg education, the prior art would have achieved it. Applicant states that the claimed Tregs consistently produce high Il-10 and high TGFbeta proves that these functional attributes are further limiting and uniquely enabled by specific “pulsing” interactions with the complex islet EV cargo described in claim 1.
This has been considered but not found persuasive. It appears by applicant’s own reasoning that the inventive Tregs of claim 1 inherently comprise the features of dependent claims 10-14. Further claim 1, section (c) has been amended to require that the reprogrammed Treg phenotype is characterized by significantly increased secretion of Il-10 and TGFbeta, and decreased secretion of IFNgamma and TNFalpha compared to polyclonal Treg cells, Thus claims 11 and 13 are specific features already required by claim 1. Regarding claim 14, The specification states that the preprogrammed Treg cell increases suppression of CD4+ and CD8+ T cell proliferation compared to a polyclonal Treg Applicant’s argument that these traits are a specific transformation result not a property of any generic Treg education are unpersuasive regarding this rejection because claim 1 is not drawn to any generic Treg education but the specific inventive method.
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.
Claim 23 is 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.
Claim 23 is vague and indefinite because it is unclear if the NTPDase3, GLP-1R or GPR44 are also required to be humanized.
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.
The rejection of claim 26 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for scope of enablement is withdrawn in light of applicant’s amendment
The rejection of claim 23 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 is maintained for reasons of record. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 23 is reliant on a genus of CAR comprising an antibody region comprising a FXTD2, NTPDase3, GLP1R or GRP44 binding domain.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
In the instant case, the antibody binding domains for FXTD2, NTPDase3, GLP1R or GRP44 must be described in a way which links structure of the antibody binding domain to the function of binding FXTD2, NTPDase3, GLP1R or GRP44, such as the sequences for the CDRs in the antibody heavy and light chains, or the sequence of the heavy chain variable region and the sequence of the light chain variable region. The specification has failed to describe this minimal structure coupled with the required binding function. Thus, one of skill in the art would not be able to envisage an antibody region that bound to FXTD2, NTPDase3, GLP1R or GRP44. One of skill in the art would reasonably conclude that applicant was not in possession of the CARs comprising the required FXTD2, NTPDase3, GLP1R or GRP44 binding domains at the time of filing.
The rejection of claims 1-5, 10-15, and 24-26 under 35 U.S.C. 103 as being unpatentable over Phillips et al (Frontiers in Immunology, 2019, Vol.101, Article 148, 9 pages) in view of Rakker et al (Frontiers n Immunology, 2017, Vol. 6, Article 569, 11 pages), Hasilio et al (Scientific Reports, 2017, Vol. 7, pp. 1-14), and Rutman et al (American Journal of Transplantation, .2017, Vol. 17, suppl. 3, pp. 425-426, Abstract A47) as evidenced by De Smedt et al (European Journal of Immunology, 1997, Vol. 27, pp. 1229-1235) is withdrawn in light of applicant’s arguments..
Applicant argues that one of skill in he art would not use EV to load CD14+ monocytes because Rutman et al teaches that islet-derived EV internalized by CD14+ monocytes triggers pro-inflammatory cytokine production, including increased TNF-alpha and Il-6. It is further noted that Hasilo et al teach that EV detected in islet-conditioned media may contribute to stimulation of an inflammatory response as they carry proteins involved in apoptotic pathways, chaperone or complement activation which could pose a problem for regenerative cellular therapies to treat T1DM (page 8, lines 10-12 of the first full paragraph). Applicant’s argument is persuasive.
Applicant further argues unexpected results in that the cargo-educated Tregs of the invention maintain a powerful suppression of CD4+ and CD8+ T cell proliferation even at extreme 128:1 dilution and that the aTregs produced by the claimed method produce significantly higher levels of Il-10 and TGF-beta compared to the standard polyclonal Treg described in the art. Applicant’s argument is persuasive.
The rejection of claims 1-8, 10-15, and 24-26 under 35 U.S.C. 103 as being unpatentable over Phillips et al Rakker et al, Hasilio et al, Rutman et al and de Smedt et al as applied to claims 1-5, 10-15, and 24-26 above, and further in view of Tarbell et al (Journal of Experimental Medicine, 2007, Vol,. 204, pp. 191-201); and
The rejection of claims 1-5, 10-15, 20, 22, and 24-26 under 35 U.S.C. 103 as being unpatentable over Phillips et al Rakker et al, Hasilio et al, Rutman et al and De Smedt et al as applied to claims 1-5, 10-15, and 24-26 above, and further in view of the abstract of Imam and Jaume (Journal of the Endocrine Society, 2019, Vol, 3, Suppl. 1, April-May, Abstract MON-LB033) is withdrawn in light of applicant’s arguments, above..
Allowable Subject Matter
Claim\s 1-8, 15, 20, 22, 24, and 26 are allowed.
Conclusion
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 KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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