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 .
Amendments
In the reply filed 11/26/2025, Applicant has amended Claims 10, and cancelled Claims 11 and 16.
Claims 1-9 and 17-20 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 10, 12, and 13 are under consideration.
Withdrawn Claim Objections
The objection to Claim 10 has been withdrawn due to Applicant’s amendment to define the abbreviation caTLR4.
Withdrawn 35 USC § 102
The prior rejection of Claim 10 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011). is withdrawn in light of Applicant’s amendment of Claim 10 to limit the tetramix of nucleic acids to those encoding a IL-10RA decoy, caTLR4, CD40L and IFN-gamma, which is a limitation Beech does not anticipate. Specifically, Beech claims a composition comprising nucleic acids encoding the IL10R decoy, IFN-gamma, and CD70.
Withdrawn 35 USC § 103
The prior rejection of Claims 10 and 13 under 35 U.S.C. 103 as being unpatentable over Thielemans (US Patent 8,476,419, patented 7/02/2013) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011), and Braughler (US2013/0149290, prior art of record) is withdrawn in light of Applicant’s arguments that the nucleic acids taught to make obvious the IL-10RA decoy do not meet the specification’s special definition of decoy receptor.
The prior rejection of Claims 10, 12 and 13 under 35 U.S.C. 103 as being unpatentable over Thielemans (US Patent 8,476,419, patented 7/02/2013) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011), Braughler (US2013/0149290, prior art of record), and Pan et al. (Immuno Letter, 2004, 94:141-151) is withdrawn in light of Applicant’s arguments directed to the special definition of decoy receptor.
New Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 10, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Thielemans (US Patent 8,476,419, patented 7/02/2013, prior art of record), in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011, prior art of record), De Smedt et al. (Eu J Immuno, 1997, 27:1229-1235), Kamanaka et al., (J Exp Med, 2011, 208:1027-1040), and Pan et al. (Immuno Letter, 2004, 94:141-151, prior art of record)
In regard to claims 10 and 12, Thielemans claims a composition for improving the immunostimulatory characteristics of dendritic cells comprising a combination of mRNA molecules that encode caTLR4, CD40L, and CD70 (see Claim 1 of Thielemans).
However in regard to claim 10, Thielemans is silent with respect to polynucleotide that encodes IL-10RA decoy.
Beech is directed to the genetic engineering of dendritic cells (Title). With respect to claim 10, Beech claims a nucleic acid vector-based comprising a polynucleotide encoding multiple immunomodulatory proteins comprising an IL-10 receptor subunit dominant negative (alias IL-10R DN), and CD70 (see Claim 1 of Beech).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the nucleic acid composition for improving the effectiveness of dendritic cells to treat cancer as taught by Thielemans, and to combine a nucleic acid encoding an IL-10R dominant negative receptor as taught by Beech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to inhibit IL-10 in dendritic cells because it was well known that IL-10 receptor activation interferes with dendritic cell functional maturation (see Discussion of De Smedt et al. 1997), while Thielmans teaches that the intended use of the nucleic acid composition was to transfect immature dendritic cells to stimulate maturation and thereby enhance T cell immunity (col 4, 3rd to 5th para.).
Furthermore, since both nucleic acid compositions are for improving the effectiveness of dendritic cells for treating cancer, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to the alpha subunit of the IL-10RA decoy as per claim 10, as there are only two (i.e, alpha and beta), one of ordinary skill would have immediately envisioned the alpha option.
However, in regard to the specification defined structure of the IL-10RA decoy of claim 10, Beech is silent to the IL-10RA DN nucleic acid encoding a decoy receptor that is a variant of the IL-10 receptor alpha subunit lacking the intracellular domain and the associated JAK1 domain.
[AltContent: textbox ([img-media_image1.png])]Nevertheless, Kamanaka et al. (2011) teaches a nucleic acid encoding a IL-10RA dominant negative for expression in immune cells to inhibit 1L-10 signaling (see excerpt from Fig. 1A, adjacent). Specifically, Kamanaka teaches the nucleic acid encodes a IL-10RA DN is truncated at proline 265 just beneath the transmembrane domain (p. 1038, Materials & Methods, thus for all intents and purposes the taught IL-10RA DN is a “decoy” that is a variant of the IL-10 receptor alpha subunit lacking the intracellular domain and the associated JAK1 domain.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the nucleic acid composition for improving the effectiveness of dendritic cells to treat cancer comprising a nucleic acid encoding the IL-10RA dominant negative as suggested by Thielemans and Beech, and choose the IL-10RA decoy nucleic acid as taught by Kamanaka with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
However in regard to claim 10, although Thielemans suggest the composition further comprise IFN-gamma protein as a soluble factor to stimulate dendritic cells (see Claim 8 of Thielemans), Thielemans is silent with respect to polynucleotide that encodes IFN-gamma.
Nevertheless, as stated supra, Beech is directed to the genetic engineering of dendritic cells (Title). With respect to claim 10, Beech claims a nucleic acid vector-based comprising a polynucleotide encoding multiple immunomodulatory proteins comprising an IL-10 receptor subunit dominant negative (IL-10 R DN), CD70, and IFN-gamma (see Claim 1 of Beech).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the nucleic acid composition for improving the effectiveness of dendritic cells to treat cancer as taught by Thielmans, and to combine a nucleic acid encoding an IFN-gamma as taught by Beech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Pan et al., who teaches that when dendritic cells genetically engineered with nucleic acids encoding IFN-gamma promotes dendritic cell maturation with increased expression of costimulatory molecules, promotes secretion of proinflammatory cytokines, and more potently activate T cells (Abstract, Results, Sections 3.3-3.5). Furthermore, since both nucleic acid compositions are for improving the effectiveness of dendritic cells for treating cancer, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to claim 12, as stated supra, Thielemans claims CD70 (see Claim 1 of Thielemans).
In regard to claim 13, Thielemans teaches the composition further comprises a pharmaceutically acceptable adjuvant (col 2, last para.).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/26/2025 are acknowledged.
First, Applicant argues that instant specification provides a special definition of decoy receptor, while Beech only recites a generic IL-10R DN.
Second, Applicant kindly points out that Thielemans is patent number 8,476,419, and argues that although Thielemans teaches the trimix nucleic acids that encode caTLR4, CD40L, and CD70 for improving the immunostimulatory characteristics of dendritic cells, they are silent to combining nucleic acid that encode a IL-10RA decoy and IFN-gamma.
Third, Applicant argues that the tetramix combination of nucleic acid (i.e., IL-10RA decoy, caTLR4, CD40L, and IFN-g) yielded unexpected results compared to the trimix combination of the prior art of Thielemans (CD40L, CD70, caTLR4), when transfected into dendritic cells (DCs). Specifically, Applicant argues that tetramix transfected DCs secreted 86x more IL-12 and 5x less IL-10 that the trimix transfected DCs.
Applicant's arguments have been fully considered and they are found partially persuasive.
In regard to Applicant’s first arguments, the Examiner has found Applicant’s arguments persuasive and has amended the rejection in include the prior art of Kamanaka et al. (2011) who teach an IL-10RA decoy to inhibit IL-10 signaling in immune cells.
In regard to Applicant’s second argument, Applicant is reminded that a 35 U.S.C. § 103(a) based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In instant case, Thielemans teaches the trimix of CD40L, CD70, and caTLR4 for improving the immunostimulatory characteristics of DCs, while Beech et al. make obvious to combine an IL-10RA decoy for improving the immunostimulatory characteristics of DCs, and Pan et al. make obvious to combine IFN-gamma for improving the immunostimulatory characteristics of DCs. As stated supra, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to Applicant’s third arguments, as a first matter, Applicant’s purported unexpected results are not commensurate in scope with the rejected claims. Applicant’s function effects of the nucleic acid compositions refers only to dendritic cells comprising said nucleic acids. Importantly, in order to complete the art of record and to rebut Applicant's arguments, Applicant is directed to the work of Kamanaka et al., (J Exp Med, 2011, 208:1027-1040), which demonstrate that well before the time of invention it was known that the effects of IL-10 decoy receptors were cell type specific. For example, Kamanaka evidences that unlike the role of IL-10 in APCs that inhibits the Th1-type differentiation of immature dendritic cells, when an IL-10RA DN nucleic acid is specifical expressed in T cells (using a CD4 specific promoter), the differentiation of naïve T cells was not inhibited (p. 1038, Discussion, 1st para., see Fig. 7).
As a second matter, the effects on the IL-12/IL-10 on dendritic cells using the claimed composition does not appear to be unexpected and are merely confirmatory that the invention worked as intended. For example, DeSmedt teaches that when DCs are cultured with IL-10, there is up to a 12x reduction in IL-12 secretion (see Table 1, Expt. 2). Furthermore, Pan teaches that DCs expressing IFN-g exhibit nearly a 5x increase in IL-12 secretion (see Fig. 6). Thus, the prior art suggests nearly a 60x increase in IL-12 production with the inclusion of an IL-10RA decoy and IFN-g, thereby indicating that Applicant’s results amount to an affirmation that the claimed subject matter functions as it was intended to function. This is not relevant to the issue of nonobviousness of the claimed subject matter and provides no objective evidence thereof.
Withdrawn Double Patenting
The prior rejection of Claims 10 and 13 on the grounds of nonstatutory double patenting over claims 1-6 of U.S. Patent No. 8,476,419 (Thielemans et al., Patented 7/02/2013) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011) and Braughler (US2013/0149290, prior art of record) is withdrawn in light of Applicant’s arguments directed to the special definition of decoy receptor.
The prior rejection of Claim 12 on the grounds of nonstatutory double patenting over claims 1-6 of U.S. Patent No. 8,476,419 (Thielemans et al., Patented 7/02/2013) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011) and Braughler (US2013/0149290, prior art of record), in further view of Pan et al. (Immuno Letter, 2004, 94:141-151) is withdrawn in light of Applicant’s arguments directed to the special definition of decoy receptor.
The prior rejection of Claims 10 and 13 on the grounds of nonstatutory double patenting over claims 1-3 of U.S. Patent No. 10,159,755 (Heirman & Thielemans et al., Patented 12/25/2018) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011) and Braughler (US2013/0149290, prior art of record) is withdrawn in light of Applicant’s arguments directed to the special definition of decoy receptor.
The prior rejection of Claim 12 on the grounds of nonstatutory double patenting over claims 1-3 of U.S. Patent No. 10,159,755 (Heirman & Thielemans et al., Patented 12/25/2018) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011) and Braughler (US2013/0149290, prior art of record) in further view of Pan et al. (Immuno Letter, 2004, 94:141-151) is withdrawn in light of Applicant’s arguments directed to the special definition of decoy receptor.
The prior rejection of Claims 10 and 13 on the grounds of nonstatutory double patenting over claims 1-6 of U.S. Patent No. 10,864,284 (Heirman & Thielemans et al., Patented 12/15/2020) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011) and Braughler (US2013/0149290, prior art of record) is withdrawn in light of Applicant’s arguments directed to the special definition of decoy receptor.
The prior rejection of Claim 12 on the grounds of nonstatutory double patenting over claims 1-6 of U.S. Patent No. 10,864,284 (Heirman & Thielemans et al., Patented 12/15/2020) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011) and Braughler (US2013/0149290, prior art of record) in further view of Pan et al. (Immuno Letter, 2004, 94:141-151) is withdrawn in light of Applicant’s arguments directed to the special definition of decoy receptor.
New 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 obviousness-type 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); 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) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
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 10, 12 and 13 are rejected on the grounds of nonstatutory double patenting over claims 1-6 of U.S. Patent No. 8,476,419 (Thielemans et al., Patented 7/02/2013) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011, prior art of record), De Smedt et al. (Eu J Immuno, 1997, 27:1229-1235), Kamanaka et al., (J Exp Med, 2011, 208:1027-1040), and Pan et al. (Immuno Letter, 2004, 94:141-151, prior art of record)
The subject matter claimed in the instant application is disclosed in the referenced patent as follows: the composition comprising mRNA molecules encoding CD40L, CD70, and caTLR4 makes obvious the nucleic acid composition of instant application. It is clear that elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are silent to nucleic acids encoding a IL-RA decoy and IFN-gamma.
However in regard to the IL-10RA decoy of claim 10, Beech is directed to the genetic engineering of dendritic cells (Title). With respect to claim 10, Beech claims a nucleic acid vector-based comprising a polynucleotide encoding multiple immunomodulatory proteins comprising an IL-10 receptor subunit dominant negative (alias IL-10R DN), and CD70 (see Claim 1 of Beech).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have claimed the nucleic acid composition for improving the effectiveness of dendritic cells as claimed by cited patent, and to combine a nucleic acid encoding an IL-10R dominant negative receptor as taught by Beech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to inhibit IL-10 in dendritic cells because it was well known that IL-10 receptor activation interferes with dendritic cell functional maturation (see Discussion of De Smedt et al. 1997).
Furthermore, since both nucleic acid compositions are for improving the effectiveness of dendritic cells for treating cancer, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to the alpha subunit of the IL-10RA decoy as per claim 10, as there are only two (i.e, alpha and beta), one of ordinary skill would have immediately envisioned the alpha option.
However, in regard to the specification defined structure of the IL-10RA decoy of claim 10, Beech is silent to the IL-10RA DN nucleic acid encoding a decoy receptor that is a variant of the IL-10 receptor alpha subunit lacking the intracellular domain and the associated JAK1 domain.
[AltContent: textbox ([img-media_image1.png])]Nevertheless, Kamanaka et al. (2011) teaches a nucleic acid encoding a IL-10RA dominant negative for expression in immune cells to inhibit 1L-10 signaling (see excerpt from Fig. 1A, adjacent). Specifically, Kamanaka teaches the nucleic acid encodes a IL-10RA DN is truncated at proline 265 just beneath the transmembrane domain (p. 1038, Materials & Methods, thus for all intents and purposes the taught IL-10RA DN is a “decoy” that is a variant of the IL-10 receptor alpha subunit lacking the intracellular domain and the associated JAK1 domain.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to claim the nucleic acid composition for improving the effectiveness of dendritic cells to treat cancer comprising a nucleic acid encoding the IL-10RA dominant negative as suggested by cited patent in view of Beech, and choose the IL-10RA decoy nucleic acid as taught by Kamanaka with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
However in regard to claim 10, the cited patent is silent with respect to polynucleotide that encodes IFN-gamma.
Nevertheless, as stated supra, Beech is directed to the genetic engineering of dendritic cells (Title). With respect to claim 10, Beech claims a nucleic acid vector-based comprising a polynucleotide encoding multiple immunomodulatory proteins comprising an IL-10 receptor subunit dominant negative (IL-10 R DN), CD70, and IFN-gamma (see Claim 1 of Beech).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to claim the nucleic acid composition for improving the effectiveness of dendritic cells as claimed by cited patent, and to combine a nucleic acid encoding an IFN-gamma as taught by Beech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Pan et al., who teaches that when dendritic cells genetically engineered with nucleic acids encoding IFN-gamma promotes dendritic cell maturation with increased expression of costimulatory molecules, promotes secretion of proinflammatory cytokines, and more potently activate T cells (Abstract, Results, Sections 3.3-3.5). Furthermore, since both nucleic acid compositions are for improving the effectiveness of dendritic cells for treating cancer, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to claim 12, as stated supra, cited patent claims CD70 (see Claim 1 of Thielemans).
In regard to claim 13, Beech teaches the composition further comprises a pharmaceutically acceptable adjuvant ([0131-0140]), which would have been obvious to claim to further improve the immunostimulatory characteristics of the dendritic cells.
Since the instant application claims are obvious over cited patent claims in view of Beech, De Smedt, Kamanaka, and Pan, said claims are not patentably distinct.
Claims 10, 12 and 13 are rejected on the grounds of nonstatutory double patenting over claims 1-3 of U.S. Patent No. 10,159,755 (Heirman & Thielemans et al., Patented 12/25/2018) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011, prior art of record), De Smedt et al. (Eu J Immuno, 1997, 27:1229-1235), Kamanaka et al., (J Exp Med, 2011, 208:1027-1040), and Pan et al. (Immuno Letter, 2004, 94:141-151, prior art of record)
The subject matter claimed in the instant application is disclosed in the referenced patent as follows: the nucleic acid vector encoding CD40L, CD70, and caTLR4 makes obvious the nucleic acid composition of instant application. It is clear that elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are silent to nucleic acids encoding a IL-RA decoy and IFN-gamma.
However in regard to the IL-10RA decoy of claim 10, Beech is directed to the genetic engineering of dendritic cells (Title). With respect to claim 10, Beech claims a nucleic acid vector-based comprising a polynucleotide encoding multiple immunomodulatory proteins comprising an IL-10 receptor subunit dominant negative (alias IL-10R DN), and CD70 (see Claim 1 of Beech).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have claimed the nucleic acid composition for improving the effectiveness of dendritic cells as claimed by cited patent, and to combine a nucleic acid encoding an IL-10R dominant negative receptor as taught by Beech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to inhibit IL-10 in dendritic cells because it was well known that IL-10 receptor activation interferes with dendritic cell functional maturation (see Discussion of De Smedt et al. 1997).
Furthermore, since both nucleic acid compositions are for improving the effectiveness of dendritic cells for treating cancer, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to the alpha subunit of the IL-10RA decoy as per claim 10, as there are only two (i.e, alpha and beta), one of ordinary skill would have immediately envisioned the alpha option.
However, in regard to the specification defined structure of the IL-10RA decoy of claim 10, Beech is silent to the IL-10RA DN nucleic acid encoding a decoy receptor that is a variant of the IL-10 receptor alpha subunit lacking the intracellular domain and the associated JAK1 domain.
[AltContent: textbox ([img-media_image1.png])]Nevertheless, Kamanaka et al. (2011) teaches a nucleic acid encoding a IL-10RA dominant negative for expression in immune cells to inhibit 1L-10 signaling (see excerpt from Fig. 1A, adjacent). Specifically, Kamanaka teaches the nucleic acid encodes a IL-10RA DN is truncated at proline 265 just beneath the transmembrane domain (p. 1038, Materials & Methods, thus for all intents and purposes the taught IL-10RA DN is a “decoy” that is a variant of the IL-10 receptor alpha subunit lacking the intracellular domain and the associated JAK1 domain.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to claim the nucleic acid composition for improving the effectiveness of dendritic cells to treat cancer comprising a nucleic acid encoding the IL-10RA dominant negative as suggested by cited patent in view of Beech, and choose the IL-10RA decoy nucleic acid as taught by Kamanaka with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
However in regard to claim 10, the cited patent is silent with respect to polynucleotide that encodes IFN-gamma.
Nevertheless, as stated supra, Beech is directed to the genetic engineering of dendritic cells (Title). With respect to claim 10, Beech claims a nucleic acid vector-based comprising a polynucleotide encoding multiple immunomodulatory proteins comprising an IL-10 receptor subunit dominant negative (IL-10 R DN), CD70, and IFN-gamma (see Claim 1 of Beech).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to claim the nucleic acid composition for improving the effectiveness of dendritic cells as claimed by cited patent, and to combine a nucleic acid encoding an IFN-gamma as taught by Beech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Pan et al., who teaches that when dendritic cells genetically engineered with nucleic acids encoding IFN-gamma promotes dendritic cell maturation with increased expression of costimulatory molecules, promotes secretion of proinflammatory cytokines, and more potently activate T cells (Abstract, Results, Sections 3.3-3.5). Furthermore, since both nucleic acid compositions are for improving the effectiveness of dendritic cells for treating cancer, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to claim 12, as stated supra, cited patent claims CD70 (see Claim 1 of Thielemans).
In regard to claim 13, Beech teaches the composition further comprises a pharmaceutically acceptable adjuvant ([0131-0140]), which would have been obvious to claim to further improve the immunostimulatory characteristics of the dendritic cells.
Since the instant application claims are obvious over cited patent claims in view of Beech, De Smedt, Kamanaka, and Pan, said claims are not patentably distinct.
Claims 10, 12 and 13 are rejected on the grounds of nonstatutory double patenting over claims 1-6 of U.S. Patent No. 10,864,284 (Heirman & Thielemans et al., Patented 12/15/2020) in view of Beech et al. (US2011/0268766, filed 10/08/2009, published 11/03/2011, prior art of record), De Smedt et al. (Eu J Immuno, 1997, 27:1229-1235), Kamanaka et al., (J Exp Med, 2011, 208:1027-1040), and Pan et al. (Immuno Letter, 2004, 94:141-151, prior art of record)
The subject matter claimed in the instant application is disclosed in the referenced patent as follows: the composition comprising mRNA molecules encoding CD40L, CD70, and caTLR4 makes obvious the nucleic acid composition of instant application. It is clear that elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are silent to nucleic acids encoding a IL-RA decoy and IFN-gamma.
However in regard to the IL-10RA decoy of claim 10, Beech is directed to the genetic engineering of dendritic cells (Title). With respect to claim 10, Beech claims a nucleic acid vector-based comprising a polynucleotide encoding multiple immunomodulatory proteins comprising an IL-10 receptor subunit dominant negative (alias IL-10R DN), and CD70 (see Claim 1 of Beech).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have claimed the nucleic acid composition for improving the effectiveness of dendritic cells as claimed by cited patent, and to combine a nucleic acid encoding an IL-10R dominant negative receptor as taught by Beech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to inhibit IL-10 in dendritic cells because it was well known that IL-10 receptor activation interferes with dendritic cell functional maturation (see Discussion of De Smedt et al. 1997).
Furthermore, since both nucleic acid compositions are for improving the effectiveness of dendritic cells for treating cancer, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to the alpha subunit of the IL-10RA decoy as per claim 10, as there are only two (i.e, alpha and beta), one of ordinary skill would have immediately envisioned the alpha option.
However, in regard to the specification defined structure of the IL-10RA decoy of claim 10, Beech is silent to the IL-10RA DN nucleic acid encoding a decoy receptor that is a variant of the IL-10 receptor alpha subunit lacking the intracellular domain and the associated JAK1 domain.
[AltContent: textbox ([img-media_image1.png])]Nevertheless, Kamanaka et al. (2011) teaches a nucleic acid encoding a IL-10RA dominant negative for expression in immune cells to inhibit 1L-10 signaling (see excerpt from Fig. 1A, adjacent). Specifically, Kamanaka teaches the nucleic acid encodes a IL-10RA DN is truncated at proline 265 just beneath the transmembrane domain (p. 1038, Materials & Methods, thus for all intents and purposes the taught IL-10RA DN is a “decoy” that is a variant of the IL-10 receptor alpha subunit lacking the intracellular domain and the associated JAK1 domain.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to claim the nucleic acid composition for improving the effectiveness of dendritic cells to treat cancer comprising a nucleic acid encoding the IL-10RA dominant negative as suggested by cited patent in view of Beech, and choose the IL-10RA decoy nucleic acid as taught by Kamanaka with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
However in regard to claim 10, the cited patent is silent with respect to polynucleotide that encodes IFN-gamma.
Nevertheless, as stated supra, Beech is directed to the genetic engineering of dendritic cells (Title). With respect to claim 10, Beech claims a nucleic acid vector-based comprising a polynucleotide encoding multiple immunomodulatory proteins comprising an IL-10 receptor subunit dominant negative (IL-10 R DN), CD70, and IFN-gamma (see Claim 1 of Beech).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to claim the nucleic acid composition for improving the effectiveness of dendritic cells as claimed by cited patent, and to combine a nucleic acid encoding an IFN-gamma as taught by Beech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Pan et al., who teaches that when dendritic cells genetically engineered with nucleic acids encoding IFN-gamma promotes dendritic cell maturation with increased expression of costimulatory molecules, promotes secretion of proinflammatory cytokines, and more potently activate T cells (Abstract, Results, Sections 3.3-3.5). Furthermore, since both nucleic acid compositions are for improving the effectiveness of dendritic cells for treating cancer, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to claim 12, as stated supra, cited patent claims CD70 (see Claim 1 of Thielemans).
In regard to claim 13, Beech teaches the composition further comprises a pharmaceutically acceptable adjuvant ([0131-0140]), which would have been obvious to claim to further improve the immunostimulatory characteristics of the dendritic cells.
Since the instant application claims are obvious over cited patent claims in view of Beech, De Smedt, Kamanaka, and Pan, said claims are not patentably distinct.
RESPONSE TO ARGUMENTS
Applicant's arguments regarding the double patenting rejections filed on 11/26/2025 are acknowledged and have been addressed above.
Conclusion
No claims are allowed.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631