DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Applicant's amendment and remarks, filed 8/13/25, are acknowledged.
Claims 7-8, 11 have been amended.
Claims 19 has been added.
Claims 7-9, 11, 14-19 are pending.
Claims 14-18 are withdrawn as being directed to a non-elected invention
Claims 7-9, 11, and 19 are being acted upon.
In view of Applicant’s claim amendments, the previous grounds of rejection are withdrawn.
The following are new grounds of rejection necessitated by Applicant’s amendment.
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 7-9, 11, 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.
Claim 7 recites the limitation "the administration" in line 12 There is insufficient antecedent basis for this limitation in the claim.
Claim 19 recites the limitation "the expanded population of autologous Treg cells" in line 2 There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 7-9 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Putnam, 2009 (of record), in view of Trzonkowski, Cytometry 2009 (of record) and 20110300119 (of record).
Putnam teaches a method of expanding human Treg cells comprising providing sorted CD4+CD127lo/-CD25+ Tregs from subjects with type 1 diabetes. Putnam teaches that the subjects include those that are 17 years of age, i.e. a child, see page 652, in particular). Putnam teach propagating the Treg cells with anti-CD3/CD28 magnetic beads and IL-2 in a medium containing 10% inactivated human serum for 7-14 days (see page 653 and Fig. 3, in particular). Said sorted Tregs would comprise at least a subpopulation of CD4+CD25highCD127- T cells, and would also be CD3+, since CD3 is inherently expressed by CD4 T cells. Putnam teaches that the Treg express more than 90% FoxP3+ (see Fig. 4 and Fig. 5, in particular). Putnam teaches using flow cytometry to obtain a 98% pure population of the Tregs (see page 653, in particular).
The reference differs from the claimed invention in that it does not explicitly teach using autologous serum.
The ‘119 publication teaches a method of expanding a population of human Tregs comprising providing a population of Treg cells, propagating the Treg cells ex-vivo in a medium supplemented with IL-2, autologous inactivated serum and anti-CD3/CD28 magnetic beads (i.e. artificial antigen presenting cells in the shape of a sphere) for 7-14 days (see page 8-9). The ‘191 publication teaches providing the Tregs by sorting for CD4+CD25+CD127low/- Treg cells (see page 8-9, in particular).
Trzonkowski teaches that there are advantages to using autologous serum since it is less likely to transmit infectious disease and reduces the risk of anaphylactic reactions (see page 183, in particular). Trzonkowski teaches that IL-2 is a crucial Treg growth factor and is used in cultures at amounts of 1,000 UI/ml (see page 181 and 182, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use autologous serum, as taught by the ‘119 publication and Trzonkowski, as the type of serum in the Treg cultures of Putnam. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘119 publication and Trznokowski teach that it can be used for expanding Tregs and that it has advantages since it is less likely to transmit infectious disease and reduces the risk of anaphylactic reactions. Furthermore, it would be obvious to optimize the concentration of IL-2, and the recited amounts are well within the purview of the ordinary artisan. For example, Trzonkowski teaches the importance of IL-2 in expanding Tregs and that it can be used in amounts of 1000 U/ml of IL-2. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Regarding the limitation that administration of the Treg cells results in certain dosages results in an increase in the C-peptide level, the present claims are directed to a method of producing Tregs and do not require administration. Putnam teaches Tregs structurally and functionally identical to those of the instant claims, produced by a substantially identical process (with the only different being the use of donor serum instead of autologous serum in the cultures). Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
In other words, the claimed function is merely an inherent or latent property of the Treg cells of the prior art. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Claims 7-9 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Marek, 2011 (of record), in view of Trzonkowski, Cytometry 2009 (of record) and 20110300119 (of record).
The reference differs from the claimed invention in that it does not explicitly teach using autologous serum.
The ‘119 publication teaches a method of expanding a population of human Tregs comprising providing a population of Treg cells, propagating the Treg cells ex-vivo in a medium supplemented with IL-2, autologous inactivated serum and anti-CD3/CD28 magnetic beads (i.e. artificial antigen presenting cells in the shape of a sphere) for 7-14 days (see page 8-9). The ‘191 publication teaches providing the Tregs by sorting for CD4+CD25+CD127low/- Treg cells (see page 8-9, in particular).
Trzonkowski teaches that there are advantages to using autologous serum since it is less likely to transmit infectious disease and reduces the risk of anaphylactic reactions (see page 183, in particular). Trzonkowski teaches that IL-2 is a crucial Treg growth factor and is used in cultures at amounts of 1,000 UI/ml (see page 181 and 182, in particular). Trzonkowski teaches that FACS sorting can provide Treg populations that are greater than
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use autologous serum, as taught by the ‘119 publication and Trzonkowski, as the type of serum in the Treg cultures of Marek. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘119 publication and Trznokowski teach that it can be used for expanding Tregs and that it has advantages including lower likelihood of infectious disease transmission and anaphylactic reaction.
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 7-9, 11, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,072,779, in view of 20110300119, Trzonkowski, 2009, Putnam, 2009. The ‘779 patent claims a method of in vitro expansion of CD4+CD25highCD127-/lowFoxP3+ Tregs comprising expanding the Tregs for at least 14 days in a culture with magnetic beads coated with anti-CD3 and anti-CD28 and with IL-2. It would be obvious to include autologous inactivated human serum and to use a 10% amount, as well as to use 1000 U/ml IL-2 based on the teachings of the ‘119 publication and Trzonkowski, for the same reasons set forth above. Furthermore, it would be obvious to use the Treg sorting protocol of Trzonkowski or Putnam, as well as to achieve greater than 97% Tregs, or greater than 90% FoxP3+ Tregs, based on the teachings of Trzonkowski and Putnam for the same reasons set forth above. Furthermore, it would be obvious to provide the Tregs from a child with type 1 diabetes, as taught by Putnam since the references teach that they provide for a population of suppressive Tregs which can be tested for treating type 1 diabetes. As noted above, the claimed functional property would be inherent/latent property of CD4+CD25highCD127-/lowFoxP3+ Tregs.
Claims 7-9, 11, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,944,672, in view of 20110300119, Trzonkowski, 2009, Putnam, 2009 (all of record).
The ‘672 patent claims a method of treating a child with type 1 diabetes comprising administering to the child CD3(+)CD4(+)CD25(high)CD127(−) autologous Treg cells expanded ex vivo from the child in an amount between 10×106 cells/kg body weight and 30×106 cells/kg body weight, wherein more than 90% of the Treg cells express factor FoxP3, and wherein the administration of the Treg cells results in an increase in the C-peptide level in the child at 5 months after the administration. It would be obvious to make the Tregs by the claimed process, based on the teachings of the ‘119 publication, Putnam, and Trzonkowski for the same reasons set forth above. Alternatively, the ‘672 patent also claims product by process steps explaining how the administered Tregs can be made by providing CD3(+)CD4(+)CD25[high]CD127(−) Treg using a sorting device, wherein the sorted cells comprise a Treg cell population having a purity of at least 97%; propagating the sorted T lymphocyte cells ex vivo with 1000 U/ml interleukin-2 and 10% autologous inactivated serum in the presence of magnetic sphere and coated by anti-CD3 and anti-CD28 antibodies. It would therefore also be obvious to perform a combination method involving first producing the Tregs using the product by process methodology specifically claimed in the ‘672 patent and also further administering the Tregs.
It is noted that even though the instant application is a divisional of the application from which the ‘672 patent issued, claim 19 is not consonant with the restriction requirement issued in the parent application, which divided the claims into method of treatment comprising administering T regs and methods of producing Tregs. In contrast, Claim 19 is directed to a combination method requiring both producing Tregs and administering Tregs. Therefore, a prohibition against nonstatutory double patenting rejections under 35 U.S.C. 121 does not apply, since the claims of the application under examination and claims of the other application/patent are not consonant with the restriction requirement made by the examiner, and the claims have been changed in material respects from the claims at the time the requirement was made by including additional claims not consonant in scope with the original claims subject to restriction in the parent. Symbol Technologies, Inc. v.Opticon, Inc., 935 F.2d 1569, 19 USPQ2d 1241 (Fed. Cir. 1991); Gerber Garment Technology, Inc. v. Lectra Systems, Inc., 916 F.2d 683, 16 USPQ2d 1436 (Fed. Cir. 1990). In order for consonance to exist, the line of demarcation between the independent and distinct inventions identified by the examiner in the requirement for restriction must be maintained. 916 F.2d at 688, 16 USPQ2d at 1440.
No claim is allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644