DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 5/13/26, are acknowledged.
Claims 1, 21, 34, 83, 84, and 126 have been amended.
Claims 1-4, 6, 11, 16-17, 21-22, 29, 34, 37, 43, 46, 50, 55, 60, 65, 70, 75, 80, 82-84, 88, 90, 92-93, 98-103, and 121-124 and 126 are pending.
Claims 121-124 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claims 2-4, 6, 11, 16-17, 22, 29, 37, 43, 46, 50, 55, 60, 65, 70, 75, 80 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species.
Claims 1, 21, 34, 82-84, 88, 90, 92-93, 98-103, and 126 are being acted upon.
The rejections of record have been modified to the extent necessary to address Applicant’s claim amendments.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1, 21, 34, 82-84, 88, 90, 92-93, 98-103, and 126 are rejected 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. The claim(s) 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification and the claims as originally filed do not provide support for the invention as now claimed, specifically:
A) A method for enhancing tumor homing, a method of modulating immune activity of an antigen presenting cell, a method of enhancing the function of an antigen presenting cell comprising incubating with two or more different mRNAs wherein “a first mRNA encodes CD62L and/or CCR7 and a second mRNA encodes a membrane-bound IL-2, a membrane bound IL-12a, or a membrane bound IL-12b”. (Claim 1, 21, and 34 and dependent claims).
B) A method for enhancing the function of an antigen presenting cell comprising incubating with two or more different mRNAs, “wherein a third mRNA encodes CD86” (claim 126).
C) A method of modulating immune activity of an antigen presenting cell and a method of enhancing the function of an antigen presenting cell, wherein the antigen and the first mRNA encoding CD62L and/or CCR7 increases homing of the antigen presenting cell to a site for T cell activation by about 2-fold or more, and wherein the antigen and the second mRNA encoding membrane bound IL-2, membrane bound IL-12a, or membrane bound IL-12b increases an antigen specific T cell response by 2 fold (Claim 21, and 34 and dependent claims).
D) A method for increasing tumor homing wherein the first mRNA encoding CD62L and/or CCR7 increases tumor homing by about 5% or more compared to an antigen presenting cell that does not comprise the first mRNA (claim 1 and dependent claims).
Applicant indicates that support for the new limitations can be found in paragraphs 76-78, 99, 505 and 508, and Fig. 2b of the specification.
A review of the specification fails to reveal support for the new limitations.
Regarding A), the specification discloses enhancing homing using one or more mRNAs encoding one or more of CD62L, CCR2, CCR7, CX3CR1, or CXCR4. The specification discloses another embodiment of enhancing APC function using one or more mRNAs encoding one or more of IL-2, IL-7, IL12-a, IL-12b, IL-15, IL-18 or IL-21, and that the one or more of IL-2, IL-7, IL-12a, IL-12b, IL-15, IL-18, or IL-21 are membrane bound. The specification discloses many other long lists of potential mRNA agents in the following paragraphs for enhancing viability and/or function. While the specification generically discloses that embodiments can be combined, nowhere does the specification contemplate the specific combination of mRNA required in the present claims, wherein a first mRNA encodes CD62L and/or CCR7, and a second mRNA encodes membrane bound IL-2 or membrane IL-12. The disclosure fails to provide sufficient blaze marks that would lead the ordinary artisan toward the particular combination of mRNAs now claimed among the large number of competing possibilities. See Novozymes A/S v. DuPont Nutrition Biosciences. 107 USPQ2d 1457 (Fed. Cir. 2013).
Regarding B), in paragraph 88 the specification discloses methods for enhancing function of antigen presenting cells by contacting with one or more mRNAs encoding one or more of CD70, CD80, CD86, CD40L, 4-1BBL, OX40L, CITRL or ICOSL. However, nowhere does the specification contemplate choosing CD80 from the list as a “third” mRNA combined with a first mRNA encoding CD62L and/or CCR7 and a second mRNA encoding membrane bound IL-2, IL-12a, or IL-12b.
Regarding C), in paragraph 78 the specification discloses that mRNA encoding CD62L or CCR7 can enhance homing to a site for T cell activation, such as the lymph node, and that homing to the site for T cell activation is increased by about 2 fold, 3 fold,… or 1000 fold. However, the present claims encompass 2 fold “or more” which has no upper limit. For example, the present claims would encompass 10,000 fold more. Regarding the limitation that the second mRNA encoding membrane bound IL-2, membrane bound IL-12a, or membrane bound IL-12b increases an antigen specific T cell response by 2 fold, Applicant cites paragraphs 505 and 508 as support. Paragraph 505 discloses that BMDCs loaded with OVA and IL-12 mRNA, wherein the OVA specific response was 4 fold higher with IL-12 as compared to OVA alone, and wherein IL-2 did not significantly change the antigen specific response. Paragraph 508 discloses a 2 fold increase in IFN-gamma from CD8 T cells with IL-12 mRNA. This is not adequate support for the present claims for several reasons. For example, the claims encompass “about” 2 fold, and encompass any type of T cell response. The present claims are not limited to BMDC, but encompass any APC. The present claims encompass a 2 fold increase with IL-2, which was not increased in the example cited by Applicant. The present claims require membrane bound IL-2, IL-12a, or IL-12b, which is also not disclosed in the example cited by Applicant. It is noted that the claims also recite that “the antigen” and the first mRNA enhances homing, and the specification does not disclose antigens that enhance homing, as claimed.
Regarding D), Applicant cites paragraphs 76-78 as support. In paragraph 76, the specification discloses enhancing homing of antigen presenting cells by introducing an mRNA encoding CD62L or CCR7, and that in some embodiments the homing of an antigen presenting cell to a site for T cell activation is increased by any one of 5%, 10%, 20%, 30%... or 100%. However, the claims do not recite an increase in homing to a site of T cell activation, but rather that tumor homing is enhanced. The specification in paragraph 78 discloses increasing tumor cell homing with other agents (mRNA encoding CXCR3, CCR5, VLA-4 or LFA-1), but not with CD62L or CCR7. Furthermore, the disclosure of 5% does not provide support for the limitation “or more” which has no upper limit. For example, the present claims encompass a 200% increase.
Applicant’s arguments filed 5/13/26 have been fully considered, but they are not persuasive.
Regarding A), Applicant argues that paragraph 75 and 99 describes using agents that enhance function of an APC as an agent that modulates immune activity and/or an agent that enhances homing of the APC, and that the specification clearly points toward an APC comprising an mRNA encoding a cytokine and an mRNA encoded homing factor.
Paragraph 99 discloses that in some embodiments according to any of the methods for enhancing the viability and/or function of an antigen presenting cell described herein, two or more agents that enhance the viability and/or function of the antigen presenting cell is delivered to the antigen presenting cell. In further embodiments, according to the modified antigen presenting cells described above, the two or more agents that enhance the viability and/or function of the antigen presenting cell are chosen from one or more of a tumor homing agent, an anti-apoptotic agent, a T cell activating agent, an antigen processing agent, an immune activity modulating agent, a homing receptor, or an agent that downregulates T cell inhibition. This generic statement does not point to a specific combination of a cytokine and a homing factor, as argued by Applicant.
The specification discloses long lists of each agent. The disclosure fails to provide sufficient blaze marks that would lead the ordinary artisan toward the particular combination of mRNAs now claimed among the large number of competing possibilities. See Novozymes A/S v. DuPont Nutrition Biosciences. 107 USPQ2d 1457 (Fed. Cir. 2013). For example, even if paragraph 99 would be understood to support combining an immune activity modulating agent and a homing receptor, said immune activity modulating agents are disclosed in paragraph 75 or 154 to include agents that upregulate IL-2, IL-7, IL12a, IL-12b, IL-15, IL-18, IL-21, IRF3, IRF6, TLR4, TLR8, PPRs, STING, RIG-1, AIM2, LRRFIFp1, NLPR3, type I interferon, type II interferon, type III interferon, Shp2, or an agent that downregulates express of interferon-beta . Homing receptors disclosed include CD62L, CCR2, CCR7, CX3CR1, CXCR5, CXCR3, CCR5, VLA-4, LFA-1, and CCL2 There are no blaze marks toward combining CCR7 or CD62L with membrane bound IL-2, membrane bound Il-12a, or membrane bound IL-12b, in particular, among the large number of competing possibilities.
Applicant further argues that examples 4, 5, and 7 provide blaze marks towards the claimed combination.
Examples 4 and 5 involve loading with mRNA encoding IL-2 or IL-12, wherein IL-12 increased antigen specific T cell responses to OVA, but IL-2, surprisingly, did not. Example 7 discloses with mRNA encoding CCR7 or CD62L. Nothing provides blaze marks to combination of elements claimed, wherein a first mRNA encodes CD62L and/or CCR7 and a second mRNA encodes a membrane bound IL-2, a membrane bound IL-12a, or a membrane bound IL-12b.
Regarding B), Applicant argues that example 4 discusses introducing an mRNA encoding IL-2 or IL-12, which increases antigen specific response by 4-fol,d which encompass 2-fold, and that example 5 disclose a 2-fold increase.
As noted above, the examples are not sufficient support for several reasons. For example, they do not employ membrane bound cytokines. Furthermore, Example 4 discloses that IL-2 does not enhance antigen specific T cell responses, and therefore does not support the present claims which encompass a 2 fold increase with membrane bound IL-2.
Regarding claim 126, Applicant argues that the specification discloses an agent that enhances activation of antigen presenting cells modulates expression of CD80 and/or CD86, and in example 1 discloses delivery an antigen and CD86 mRNA.
The specification does not contemplate choosing CD80 from the list as a “third” mRNA combined with a first mRNA encoding CD62L and/or CCR7 and a second mRNA encoding membrane bound IL-2, IL-12a, or IL-12b.
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.
Claim(s) 1, 21, 34, 82-84, 88, 90, 92-93, 98-103, is/are rejected under 35 U.S.C. 103 as being unpatentable over US2010/0215674, in view of WO2016/070136 (of record), Weinstein-Marom, 2016 (all of record) and WO 99/61051 (of record).
The ‘674 publication teaches a method of enhancing immunostimulatory capacity of APCs comprising introducing at least two different mRNA encoding proteins that modify the functionality of the APCs (see page 1, in particular). The ‘674 publication teaches that the at least two different mRNA encoding functional proteins are selected from a group comprising CD40L, CD40, caTLR4, IL-12p70, EL-select, CCR7 and/or 4-1BBL(see paragraph 7, in particular). This would render obvious selecting all of the mRNAs which would include a first mRNA encoding CCR7 and a second mRNA encoding IL-12p70 (i.e. IL-12a and IL-12b) as well as an “adjuvant”. The ‘674 publication teaches that the proteins are expressed at the cell surface (i.e. increasing homing, see abstract, Fig. 1, in particular). The ‘674 publication teaches further introducing said mRNA in combination with a tumor specific antigen (see abstract in particular). The ‘674 publication teaches introducing the mRNA via electroporation (see page 1, in particular). The ‘674 publication teaches that the tumor antigen can be introduced in one step using co-electroporation with an mRNA encoding the antigen, or by loading the cells with the antigen, and that the antigen can comprise total mRNA isolated from the tumor cells, or proteins lysates of the tumor cells (See page 1-2, in particular). The ‘674 publication teaches that the antigens can be processed and presented on MHC class I and class II molecules (see pages 2-3, in particular). The ‘674 publication teaches APCs are from PBMC, that the APCs can be dendritic cells, and that the cell populations comprise both CD83+ and CD83- cell subsets, i.e. a “mixed” population (see page 10 and Fig 5B, in particular). The ‘674 publication teaches that introducing the mRNA enhances the T cell stimulatory capacity of the APC and that they elicit a high T cell immune responses (see abstract in particular). See also the drawings which depict at least two fold increase in T cell simulation after introduction of mRNA.
The reference differs from the claimed invention in that it does not explicitly teach introducing the mRNA by passing a cell suspension through a cell deforming constriction cause a perturbation or using membrane bound IL-12.
WO 2016/070136 teaches a method, termed cell squeezing, for preferentially delivering a compound, such as mRNA, to the cytosol of immune cells, such as dendritic cells, comprising passing a cell suspension comprising said immune cell with said compound through a microfluidic device, wherein said device comprises a constriction of diameter of 2 um-10 um (see claim 1, 4 and the specification, particularly pages 1-3, 11, 14-16 and 20-21). WO 2016/070136 explains that the cell membrane is disrupted by passing the immune cell through constriction, and results in cell squeezing and cell deformation/perturbations to enable delivery of the compound (see page 4-5, in particular). WO 2016/070136 teaches that the constriction point is about 50% less than the diameter of the cells to be treated (see page 41, in particular). WO 2016/070136 teaches using the method to confer a homing phenotype of the cell (See page 23, in particular). WO 2016/070136 teaches that the method is more specific, with less off target effects and less toxicity as compared to electroporation or nucleotransfection methods (See pages 8-9, and 12, in particular).
WO 99/61051 teaches engineering cells to express membrane bound cytokines, such as membrane bound IL-2 and IL-12, which is advantageous since the close juxtaposition of the membrane bound cytokine, as compared to a soluble cytokine, permits greater modulating of an immune response to an antigen comprised by the cell (See pages 6 and 17, in particular).
Weinstein-Marom teach transfecting immune cells with mRNA encoding membrane bound IL-2 or membrane bound IL-12, wherein the cytokines act as potent adjuvants, while avoiding adverse systemic dissemination and consumption by competing suppressor cells.
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 the cell squeezing technique of WO 2016/070136, as the method of introducing the mRNA and antigen in the method of the ‘674 publication. The ordinary artisan would be motivated to do so with a reasonable expectation of success since WO 2016/070136 teaches that the method is suitable for use in introducing a wide variety of compounds, including mRNA into immune cells, such as dendritic cells, and that method is more specific, with less off target effects and less toxicity as compared to electroporation.
Furthermore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use membrane bound IL-2 or membrane bound IL-12, as taught by WO 99/610051 and Weinstein-Marom, as the IL-2 or IL-12 in the method made obvious above. The ordinary artisan would be motivated to do so since Weinstein-Marom and WO 99/610051 teach advantages of membrane bound forms of Il-2 and IL-12 such as avoiding adverse systemic dissemination and consumption by competing suppressor cells, and providing close juxtaposition of the membrane bound cytokine as compared to soluble cytokines which permits greater modulating of an immune response to an antigen.
Regarding the limitation that an antigen specific T cell response is enhanced at least 2-fold, this would be expected based on the teachings of the cited references. For example, the ‘674 publication teaches that introducing the mRNA enhances the T cell stimulatory capacity of the APC and that they elicit an high T cell immune responses (see abstract in particular). See also the drawings which depict at least two fold increase in T cell simulation. Furthermore, WO 99/610051 teaches engineering cells to express membrane bound cytokines permits greater modulating of an immune response to an antigen comprised by the cell. Thus, achieving at least two fold enhanced antigen specific T cell response would be well within the purview of the ordinary artisan. The ‘674 publication teaches that introduction of CCR7 into the dendritic cells promotes in vivo migration towards the lymph nodes, i.e. a site for T cell activation (see paragraph 56, in particular). Thus, the ordinary artisan would expect to increase homing by 2 fold, and additionally this would flow naturally from increasing CCR7 expression. Regarding the limitation of 5% more tumor homing, this would be a latent property of CCR7 expression.
Applicant’s arguments filed 5/13/26 have been fully considered, but they are not persuasive.
Regarding claim 1, Applicant argues that none of the cited references teach enhancing tumor homing, but rather teach homing to the lymph node. Applicant cites post-filing data demonstrating the CCR7 induces homing to lymph nodes but also tumors.
The property of also enhancing tumor cell homing would be an inherent or latent property of CCR7 expression. In other words, the references teach expression of CCR7, and therefore tumor homing would naturally flow from the expression of CCR7 which inherently induces homing to tumors and lymph nodes.
Regarding claims 21 and 34, Applicant argues that none of the cited references explicitly disclose enhancing homing by 2 fold or more, as presently claimed.
The ‘674 publication teaches that introduction of CCR7 into the dendritic cells promotes in vivo migration towards the lymph nodes, i.e. a site for T cell activation (see paragraph 56, in particular). Thus, the ordinary artisan would expect to increase homing by 2 fold, and additionally this would flow naturally from increasing CCR7 expression.
Applicant further argues that the ‘674 publication only suggests introducing IL-12 as an additional cytokine with three immunostimulatory molecules CD40L, CD70, and caTLR4, and there would be no expectation that IL-12 alone could increase T cell response compared to an antigen alone.
References may be relied upon for all that they suggest to the ordinary artisan. The ‘674 publication teaches that the at least two different mRNA encoding functional proteins are selected from a group comprising CD40L, CD40, caTLR4, IL-12p70, EL-select, CCR7 and/or 4-1BBL(see paragraph 7, in particular). For example, this would render obvious selecting any two, such as IL-12p70 and CCR7, or even all of the mRNA. The present claims are directed to a method “comprising” the recited steps and specifically encompass “two or more” mRNAs and do not exclude mRNAs encoding additional immunostimulatory proteins. The references teach that IL-12 acts as an adjuvant to increase antigen specific T cell responses.
Claim(s) 1, 21, 34, 82-84, 88, 90, 92-93, 98-103, and 126 is/are rejected under 35 U.S.C. 103 as being unpatentable over US2006/0188490, in view of WO 2016/070136, Dorrie, 2008, Weinstein-Marom, 2016 (all of record), and WO 99/61051.
The ‘490 publication teaches delivery of at least one mRNA, wherein the at least one mRNA codes for at least one tumor antigen, to PBMCs (see abstract and pages 1-2 and 4, in particular). The ’490 publication teaches a method comprising transfecting PBMC with at least one mRNA to produce an immune stimulating pharmaceutical composition (see page 1 and 4, in particular). The ‘490 publication teaches that the mRNA can also include at least one other functional segment coding for a cytokine, such as IL-2 or IL-12, and additionally coding for at least one costimulatory molecule such as CD86, and also encoding for at least one homing receptor such as CCR7, which directs the transfected cell into the lymph nodes (i.e. increases homing, see page 4, in particular). The ‘490 publication teaches that the transfected cells are further subjected to stimulation with CPG (See page 5, in particular). The ‘490 publication teaches that the antigen is MUC1, NY-ESO, or a polyepitope, i.e. an antigen capable of being processed into MHC-I and/or II restricted peptides (see page 2, in particular). Regarding the limitation of a lysate, an mRNA antigen is structurally identical whether it is in vitro transcribed or isolated from a lysate. The ‘490 publication teaches that the PBMC contain APCs and comprise a mixed population comprising T cells, B cells and dendritic cells (see page 1 and 8, in particular). The ‘490 publication teaches that the mRNA encoding the cytokine co-stimulator molecule, and homing receptor function to promote immune response and co-stimulate the immune response (See paragraph 38, in particular).
Although the ‘490 publication does not explicitly teach using three different mRNAs, as taught by Dorrie multiple immune stimulatory proteins and an antigen can be expressed in cells using a mixture of multiple different mRNAs encoding the protein and the antigen (see page 470). Dorrie teach that the method provides for high transduction efficiency and good cell survival (see page 470, in particular). Therefore, based on Dorrie, it would be obvious to use a mixture of multiple different mRNAs encoding the antigen, CCR7, CD86 and IL-2 or IL-12, as the one or more mRNA in the method of transfecting PBMC of the ‘490 publication. Selecting from the specifically discloses functional immune stimulating molecule for use in mRNA transfection, which include IL-12, CD86, and CCR7 using separate mRNAs would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385).
The references above differ from the claimed invention in that they do not explicitly teach introducing the mRNA by passing a cell suspension through a cell deforming constriction cause a perturbation or membrane bound IL-2 or membrane bound Il-12.
WO 2016/070136 teaches a method, termed cell squeezing, for preferentially delivering a compound, such as mRNA, to the cytosol of immune cells, comprising passing a cell suspension comprising said immune cell with said compound through a microfluidic device, wherein said device comprises a constriction of diameter of 2 um-10 um (see claim 1, 4 and the specification, particularly pages 1-3, 11, 14-16 and 20-21). WO 2016/070136 explains that the cell membrane is disrupted by passing the immune cell through constriction, and results in cell squeezing and cell deformation/perturbations to enable delivery of the compound (see page 4-5, in particular). WO 2016/070136 teaches that the constriction point is about 50% less than the diameter of the cells to be treated (see page 41, in particular). WO 2016/070136 teaches using the method to confer a homing phenotype of the cell (See page 23, in particular). WO 2016/070136 teaches that the method is more specific, with less off target effects and less toxicity as compared to electroporation or nucleotransfection methods (See pages 8-9, and 12, in particular).
Weinstein-Marom teach transfecting immune cells with mRNA encoding membrane bound IL-2 or membrane bound IL-12, wherein the cytokines act as potent adjuvants, while avoiding adverse systemic dissemination and consumption by competing suppressor cells.
WO 99/61051 teaches engineering cells to express membrane bound cytokines, such as membrane bound IL-2 and IL-12, which is advantageous since the close juxtaposition of the membrane bound cytokine, as compared to a soluble cytokine, permits greater modulating of an immune response to an antigen comprised by the cell (See pages 6 and 17, 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 the cells squeezing technique of WO 2016/070136, as the method of introducing the mRNA in the method of the ‘674 publication and Dorrie. The ordinary artisan would be motivated to do so with a reasonable expectation of success since WO 2016/070136 teaches that the method is suitable for use in introducing a wide variety of compounds, including mRNA into immune cells, and that method is more specific, with less off target effects and less toxicity as compared to electroporation.
Furthermore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use membrane bound IL-2 or membrane bound IL-12, as taught by WO 99/610051 and Weinstein-Marom, as the IL-2 or IL-12 in the method made obvious above. The ordinary artisan would be motivated to do so since Weinstein-Marom and WO 99/610051 teach advantages of membrane bound forms of Il-2 and IL-12 such as avoiding adverse systemic dissemination and consumption by competing suppressor cells, and providing close juxtaposition of the membrane bound cytokine as compared to soluble cytokines which permits greater modulating of an immune response to an antigen.
Regarding the limitation that an antigen specific T cell response is enhanced at least 2-fold, this would be expected based on the teachings of the cite references. For example, the ‘490 publication teaches that the mRNA encoding the cytokine co-stimulator molecule, and homing receptor function to promote immune response and co-stimulate the immune response (See paragraph 38, in particular). Furthermore, WO 99/610051 teaches engineering cells to express membrane bound cytokines permits greater modulating of an immune response to an antigen comprised by the cell. Thus, achieving at least two fold enhanced antigen specific T cell response would be well within the purview of the ordinary artisan. Regarding the limitation of 5% more tumor homing, this would be a latent property of CCR7 expression.
Applicant argues that the ‘490 publication teaches using one mRNA encoding multiple polypeptides, and although Dorrie teaches separate mRNAs, one would not be motivated to use separate mRNAs since it would increase time and costs.
Applicant’s arguments filed 5/13/26 have been fully considered, but they are not persuasive.
Applicant argues that the claims are not obvious for the same reasons set forth above.
The claims stand rejected for the reasons set forth above.
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 1, 21, 34, 82-84, 88, 90, 92-93, 98-103, and 126 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-113 of U.S. Patent No. 11,111,472 (of record), in view of US2010/0215674, (of record), Dorie, 2008, Weinstein-Marom, 2016, US 2006/0188490 and WO 99/610051.
The ‘472 patent claims a method for engineering of immune cell function in an immune cell comprising intracellular delivery of an RNA encoding a protein or a compound that confers homing or enhanced immune function, by passing a suspension comprising said immune cell through a microfluidic device comprising a constriction and contacting the immune cell with said compound to deliver said compound into the cytosol of said immune cell, wherein the constriction has a diameter of 2 μm to 10 μm (i.e. causing perturbations to allow the compound to pass into the immune cell) The ‘472 application claims that the immune cell is a T cell or a dendritic cell (i.e. antigen presenting cells). The ‘472 patent claims that the compound is an mRNA. The ‘472 patent claims that delivery of compound increases the expression of one or more markers including CD80, CCR7 and/or CD62L. The ‘472 patent also claims that the immune cells can be PBMC and that the compound can be a tumor antigen that is presented via MHC-I or MHC-II or a tumor cell lysate.
The patent differs from the claimed invention in that it does not explicitly claim two or more mRNA encoding CCR7, CD80, and IL-12.
However, it would be obvious to use a mixture of three different mRNA encoding CCR7, CD80, and IL-2 or IL-12 to increase homing and immunostimulatory function of PBMC or dendritic cells, as taught by the ‘490 publication, Dorrie, and the ‘674 publication for the reasons set forth above. Furthermore, expressing said IL-2 or IL-12 in membrane bound form would be obvious based on Weinstein-Marom and WO 99/610051 for the reasons set forth above.
Claims 1, 21, 34, 82-84, 88, 90, 92-93, 98-103, and 126 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-67 of U.S. Patent No. 10,696,944, in view of US2010/0215674, Dorie, 2008, US 2006/0188490 Weinstein-Marom and WO 99/610051.
The ‘944 patent claims a method for delivering a payload, such as RNA into immune cells, the method comprising: providing the cells in a suspension solution; passing the solution through a microfluidic channel that includes a cell-deforming constriction, wherein a diameter of the constriction is 20-99% of a diameter of the cell in the suspension solution such that a deforming force is applied to the cell as it passes through the constriction thereby causing perturbations of the cell large enough for a payload to pass through; and incubating the cell in a payload-containing solution for a predetermined time after it passes through the constriction.
The patent differs from the claimed invention in that it does not explicitly claim two or more RNA encoding CCR7, membrane bound IL-12 and CD80.
However, it would be obvious to use a mixture of three different mRNA encoding CCR7, CD80, and IL-2 or IL-12 to increase homing and immunostimulatory function of PBMC or dendritic cells, as taught by the ‘490 publication, Dorrie, and the ‘674 publication for the reasons set forth above. Furthermore, expressing said IL-2 or IL-12 in membrane bound form would be obvious based on Weinstein-Marom and WO 99/610051 for the reasons set forth above.
Applicant’s statement that the rejection be held in abeyance until the time of allowance is acknowledged.
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.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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