DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claimed in claims 1-16 and 25-27 in the reply filed on 8/1/24 was previously acknowledged. Applicants elected 4-1BBL (first genetic element), IL-12 (second genetic element), MHCI/HLA (third genetic element), B5 (R), S3 (R’), E6 (R”), 1-30 (n) and B5-S3-E6.
Upon searching the elected species (first genetic element, second genetic element, R, R’ and R”), additional species were found. Accordingly, for purposes of compact prosecution, the election of species was modified only to the extent of examining this additional species. Otherwise the election of species requirement is still retained.
In the reply filed 11/7/25, Applicants amended claims 1, 14-15, 17, 25, 27 and added NEW claims 29-30. Claims 10-13 were cancelled.
Claims 1-9 and 14-30 are pending.
Claims 17-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 1-9, 14-16 and 25-30 are under consideration.
Please note this is a 2nd Non-Final rejection due to filing of a new application (19/455,150).
Claim Objections-Withdrawn
The objections to claim 12 and 25 are withdrawn due to cancelation of claim 12 and amendment of claim 25.
Claim Rejections -Withdrawn
The rejection of claim 27 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn due to amendment of claim.
The rejection of claims 1-12 and 25-26 under 35 U.S.C. 103 as being unpatentable over Quinones-Hinojosa et al. (US 2017/0216363, cited on IDS) in view of Riley et al. (WO2005/118788,cited on IDS) is withdrawn due to amendment of the claims.
The rejection of claims 1-12 and 25-27 under 35 U.S.C. 103 as being unpatentable over Quinones-Hinojosa et al. (US 2017/0216363) and Riley et al. (WO2005/118788) in view of Hardcastle et al. (Neuro Oncol. 2016; 19(4):493-502) is withdrawn due to amendment of the claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries 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.
The rejection of claims 1-9, 14-16, 25-26 and 29-30 under 35 U.S.C. 103 as being unpatentable over Quinones-Hinojosa et al. (US 2017/0216363) and Riley et al. (WO2005/118788) in view of Bhise et al. (International Journal of Neuromedicin 2013:8, 4641-4658, cited on IDS) is maintained.
Quinones-Hinojosa et al. teach nanoparticle formulations comprising biodegradable polymers self-assembled with nucleic acid molecules (DNA or RNA) [0008]. Quinones-Hinojosa et al. teach biodegradable polymer is PBAE [0008]. Quinones-Hinojosa et al. teach and claim the nanoparticle comprising one or more bioactive molecules, wherein the bioactive molecule comprises one or more anti-cancer agents, wherein the one or more anti-cancer agents is selected from IL-2, IL-12, IL-1, IFN-alpha and IFN-beta (claims 6-7 and [0010, 0013, 0057, 0085], meeting the limitation of “genetic element that encodes a signal 3 protein” of claim 1 and the limitations of claims 5-8. Quinones-Hinojosa et al. teach the anti-cancer agents can be encapsulated in the nanoparticle [0051, 0088, 0128]. Quinones-Hinojosa et al. teach the nanoparticles can be added to process AMSCs for treating brain tumors [0012].
Quinones-Hinojosa et al. do not teach the composition comprising a first genetic element encoding a signal 2 protein. However, the teachings of Riley et al. cure this deficiency.
Riley et al. teach artificial antigen presenting cells (aAPCs). The aAPCs comprise at least one stimulatory ligand and at least one co-stimulatory ligand, where in the ligands specifically bind with a cognate molecule on a T-cell of interest, thereby mediating expansion of the T-cell (Abstract). Riley et al. teach and claim the stimulatory ligand is selected from MHC class I and the costimulatory ligand is selected from CD80, CD86, 4-1BBL and OX40L (claims 2-3, p. 5, lines 24-32). MHC class I meets the limitation of “a third genetic element that encodes a signal 1 protein” of claims 2 and 9. The costimulatory ligand selected from CD80, CD86, 4-1BBL and OX40L meets the limitation of “a first genetic element that encodes a signal 2 protein” of claim 1 and the limitations of claims 3-4. In addition, Riley teaches the aAPC also comprises a cytokine selected from the group consisting of IL-2, IL-12, IL-15, IL-21, IFN-alpha and IFN-beta (p. 6, lines 22-27). Riley teaches the invention includes methods for inducing proliferation of a T-cell expressing a known co-stimulatory molecule said method comprising contacting the T cell with an aAPC of the invention, wherein the co-stimulatory ligand binds with said known co-stimulatory molecule, thereby specifically inducing proliferation of said T-cells (last para of p. 6).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the nanoparticle of Quinones-Hinojosa et al. which discloses nanoparticles comprising signal 3 proteins to further include a genetic element encoding a signal 2 protein (e.g. CD80, CD86, 4-1BBL, OX40L) and signal 1 proteins (e.g. MHC class I) as taught by Riley et al. teach aAPCs that co-express signal 1, signal 2 and signal 3 proteins to stimulate antigen presenting T-cell responses, including T cell activation and proliferation. Given that Quinones-Hinojosa et al. already teaches a PBAE nanoparticle systems suitable for encapsulating genetic material for therapeutic use, particularly in cancer therapy, it would have been routine and a predictable design choice for a skilled artisan to co-deliver the genetic elements encoding all three types of immune signals in order to recapitulate the full spectrum of T cell activation within a single delivery vehicle. A person of ordinary skill in the art would understand that delivering the signal 1, 2 and 3 components from a single nanoparticle would ensure delivery of the signals to the same immune cell population. There is a reasonable expectation of success given that the combination is a predictable use of known immune stimulatory elements in a known delivery system.
With respect to claim 25, Riley et al. teach the active ingredients and pharmaceutically acceptable carrier (top of p. 37).
With respect to claim 26, Riley et al. teach kits comprising the aAPC and nucleic acids encoding the various proteins (p. 44).
With respect to claims 29-30, Quinones-Hinojosa et al. teach the PBAE nanoparticles can be used for non-viral gene delivery [0113, 0117, 0118]. Quinones-Hinojosa et al. teach regulatory elements such as promoters for expression control elements for gene expression [0056].
The teachings of Quinones-Hinojosa et al. and Riley et al. are presented in detail above. The references do not teach the PBAE comprises Formula I.
Bhise et al. teach that a challenge of many gene delivery applications is having a safe and effective delivery method. Bhise et al. evaluated the biodegradable PBAE and designed a polymer library to screen for polymers most promising for gene delivery (Abstract). Bhise et al. teach that PBAEs complex with DNA and promote cellular uptake, facilitated endosomal escape and allow for DNA release in the cytoplasm and subsequent transport to the nucleus (p. 4642, bottom of 1st col.).
With respect to claims 1 and 14-15, Bhise et al. teach the scheme and structure of monomers for PBAE (Fig. 1). The top structure of Fig. 1 meets the limitations of Formula I, wherein R is B3, B4, B5 or B6, wherein R’ is S3, S4 or S5 and R” is E1, E3, E4, E5, E6, E7, E8 or E9. Bhise et al. also teach Fig. 2 which discloses different combination of monomers, such as B5S3E6 (elected species), B5S3E7 and B4S5E6 (p. 4644). Bhise et al. teach the base polymer B4S4 was synthesized at a molar ratio of 1.2:1. A 1M solution of E7 amine end capping group was added to the base polymer. Fig. 2 discloses different ratios of the monomeric units.
It would have been obvious to a person of ordinary skill in the art to pick specific monomeric components used in the claimed PBAE monomers for nanoparticle formation comprising the genetic elements of Quinones-Hinojosa et al. and Riley et al. A person of ordinary skill in the art would look to the teachings of Bhise et al. disclosure of a structure function relationship analysis of various PBAE formulations and have a motivation to optimize the combination in order to optimize cellular uptake of the nanoparticles. There is a reasonable expectation of success given that Bhise et al. test multiple combination of monomers at different ratios.
With respect to claim 16, Bhise et al. teach B4S4E7 nanoparticles of approximately 100 nm (Fig. 5A).
Response to Arguments
Applicant's arguments filed 11/7/25 have been fully considered but they are not persuasive. Please note that the arguments pertaining to the Declaration will be addressed in the response to the Declaration. Applicants argue that the invention is fundamentally different from that disclosed in the cited references. Applicants argue that the Office has not made a prima facie case of obviousness for the following reasons: 1. PHOSITA would not be motivated to combine or modify Quinones-Hinojosa and Riley in v view of Bhise in a way to arrive at the claimed composition. Applicants argue that the references provide no basis for modifying the methods to arrive at the claimed invention and to do so would render Quinones-Hinojosa and Riley unsuitable for their intended purpose (killing the cancer cells), Applicants argue that the references teach away from the claimed invention. Applicants argue there is no reasonable expectation of success in combining or modifying the references to arrive at the present invention.
These arguments were considered but are not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e. reprogramming cancer cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In the instant case, the claims are product claims and not methods of use. Furthermore, as indicated above, It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the nanoparticle of Quinones-Hinojosa et al. which discloses nanoparticles comprising signal 3 proteins to further include a genetic element encoding a signal 2 protein (e.g. CD80, CD86, 4-1BBL, OX40L) and signal 1 proteins (e.g. MHC class I) as taught by Riley et al. teach aAPCs that co-express signal 1, signal 2 and signal 3 proteins to stimulate antigen presenting T-cell responses, including T cell activation and proliferation. Given that Quinones-Hinojosa et al. already teaches a PBAE nanoparticle systems suitable for encapsulating genetic material for therapeutic use, particularly in cancer therapy, it would have been routine and a predictable design choice for a skilled artisan to co-deliver the genetic elements encoding all three types of immune signals in order to recapitulate the full spectrum of T cell activation within a single delivery vehicle. A person of ordinary skill in the art would understand that delivering the signal 1, 2 and 3 components from a single nanoparticle would ensure delivery of the signals to the same immune cell population. There is a reasonable expectation of success given that the combination is a predictable use of known immune stimulatory elements in a known delivery system. The references do not teach away> MPEP 2145 teaches “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….”. In the instant case, the references do not criticize, discredit or otherwise discourage the solution claimed.
Claims 1-9, 14-16 and 25-30 are rejected under 35 U.S.C. 103 as being unpatentable over Quinones-Hinojosa et al. (US 2017/0216363), Riley et al. (WO2005/118788) and Bhise et al. (International Journal of Neuromedicin 2013:8, 4641-4658, cited on IDS) in view of Hardcastle et al. (Neuro Oncol. 2016; 19(4):493-502). This is a new rejection necessitated by amendment of the claims.
The teachings of Quinones-Hinojosa et al., Riley et al. and Bhise et al. are presented above in detail. The references do not teach the composition of claim 1 used in combination with one or more anti-cancer checkpoint inhibitor molecules, such as anti-PD-1 antibody. However, the teachings of Hardcastle et al. cure this deficiency.
Hardcastle et al. teach GBM is the most common malignant brain tumor and has a dismal prognosis. Hardcastle et al. teach that GBM is a promising strategy due to preclinical efficacy, excellent clinical safety and its ability to evoke antitumor inflammatory responses (Abstract). Hardcastle et al. teach combining anti-PD1 blockade and MV therapy can overcome immunosuppression and enhance immune effector cell responses against GBM, thereby improving therapeutic outcome (Abstract). Hardcastle et al. teach anti-PD1 antibody in combination with MV-EGFR significantly enhanced survival of mice bearing orthotopic GL261 gliomas and increased T cell influx into their brains (Fig. 3). Hardcastle et al. teach the GBM is immunosuppressive and reversal of this status by using an immune checkpoint blockade could lead to improvement outcome.
With respect to claims 27 and 28, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to combine an anti-PD1 antibody with the composition of Quinones-Hinojosa et al., Riley et al. and Bhise et al. A person of ordinary skill would look to the teachings of Quinones-Hinojosa et al. and have a motivation to include anti-PD1 because they are both for treating the same condition: brain tumors. 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.” Furthermore, a person of ordinary skill in the art would be motivated to use anti-PD1 in combination with the composition of Quinones-Hinojosa et al., Riley et al. and Bhise et al. because the teachings of Hardcastle et al. suggest combining therapies can improve therapeutic output. A reasonable expectation of success is expected given that each component is a potential treatment for brain tumors. Moreover, there is a reasonable expectation of success given incorporating an anti-PD1 antibody in the nanoparticle formulation would potentiate the immune response against the tumor, leading to improved efficacy.
Response to Arguments
Applicant's arguments filed 11/7/25 have been fully considered but they are not persuasive. Applicants argue that Hardcastle does not cure the defects of Quinones-Hinojosa and Riley.
This argument is not persuasive for the reasons presented above.
Response to Amendment
The Declaration under 37 CFR 1.132 filed 11/7/25 is insufficient to overcome the rejection of the claims as set forth in the last Office action. The Declaration stares that the invention involves methods for programming a cancer cell. The key aspect of the invention is fundamentally different from what was known in the art and taught by Quinones-Hinojosa and Riley is the need to preserve the reprogrammed cancer cell viability, not to kill the cancer cell. In contrast, the methods of the prior art involves direct killing of cancer cells (the very cancer cells that the present approach keeps alive). The Declaration states that Riley teaches that the viral transduction needs to take place ex vivo outside of the body to construct the artificial antigen presenting cell. The Declaration states that viruses are required to achieve sufficient levels of transgene expression in cancer cells in vivo, especially when involving the expression of multiple genes concurrently. The Declaration also states that Riley teaches the T cells must be extracted from a mammal, added to the aAPCs made by viruses ex vivo and then adoptively transferred back into the mammal to have a therapeutic effect. The Declaration states that Quinones-Hinojosa was based on inducing adipose derived mesenchymal stem cells ex vivo to secrete protein to directly kill cancer cells. The Declaration states that Quinones-Hinojosa does not teach or suggest the concept of a cancer antigen presenting cell. The Declaration states in contrast to the methods taught by Riley and what is known in the art, the present invention uses non-viral biodegradable materials engineers to be highly effective and to have the reprogramming happen in situ within the body without necessitating adoptive cell transfer. This is a different strategy to what was known in the art at the time. The Declaration states that the consensus at the time of filings was that cancer therapy approaches or oncolytic based necessitated designing a therapy that directly kills cancer cells rather than our invention that necessitates designing a therapy that maintains the viability of the transferred cancer cells. The Declaration states that the mere disclosure of MV therapy plus anti-PD-1 to treat glioblastoma does not necessarily mean that there will be strong synergy between PBAE cancer programming strategy. The current invention is drawn to reprogramming cancer cells into functioning as antigen presenting cells in vivo/in situ. The Declaration states the invention focuses on the essentialness of having both signal 1 and signal 2 expressed on the surface of living cancer cells, which is different from having the genetic factors delivered to the body in general or delivered to a different cell type. The Declaration states the nanoparticles disclosed and claimed in the Application also lead to increased signal 1 on the surface of the reprogramed antigen presenting cells. MHCI and II are overexpressed on the surface of the cancer cells following PBAE reprogramming and without requiring signal 2 to be genetically encoded in the NPs. The Declaration states that the approach preserves the transfected cancer cells alive to function as tAPCs resulting in stimulation of infiltrating cytotoxic CD8+ cells that recognize the tumor and strong anti-cancer effects throughout the body as shown in animal experiments on an assortment of solid tumors and IL-12. The Declaration states that the art did not contemplate non-viral reprogramming in vivo delivery systems that preserve the viability of the transfected cancer cells to antigen presenting cells as disclosed in the instant specification. Bhise et al. shows that PBAE nanoparticles can be used for partial in vitro (not in vivo) reprogramming of fibroblasts to induced pluripotent stem cell-like cells, albeit with gross karyotypic abnormalities. Bhise concluded that the PBAE nanoparticle "non-viral reprogramming methods may pose safety risks and be less efficacious than viral approaches." The Declaration states that Bhise teaches away from the use of PBAE nanoparticles, in favor of the more traditional viruses for nucleic acid gene transfer. Bhise also demonstrates the difficulty of programming cells in vitro using PBAE NPs, which is yet much easier to do than the challenges of reprogramming cells in vivo. Bhise does not suggest reprogramming of cancer cells into tumor-derived antigen-presenting cells, a concept unknown at the time. The Declaration states the art cited in the Office Action is based on inducing direct killing of cancer cells. The art neither teaches nor suggests having the target cancer cell NOT being killed, but instead preserve its viability + reprogramming it to have a phenotype of an immune cell, an antigen presenting cell. The present invention necessarily relies on the reprogrammed cancer cell not dying and remaining alive to function as an antigen presenting cell to then stimulate other immune cells through cellular contacts with itself, particularly to stimulate specific cytotoxic CD8+ T cells that have a T Cell Receptor that binds to antigens presented by the reprogrammed cancer antigen-presenting cell.
The Declaration was considered but is not persuasive. First, the claims are product claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The instant claims are not drawn to a method of reprogramming cancer cells. Nothing in the claim language requires reprogramming cancer cells. The Riley reference is used to make obvious addition of a signal 2 protein in the nanoparticle of Quinones-Hinojosa. The Riley reference is not used to make obvious viral or non-viral delivery of the nanoparticles. With respect to the argument regarding viral delivery, Quinones-Hinojosa expressly teaches biodegradable polymers such as PBAE for delivery of nucleic acids, demonstrating that non-viral delivery systems were known and used for therapeutic delivery. The argument that Bhise teaches away from PBAE is not persuasive as the references states that “…with further development the B4S3E7 bases nanoparticles may potentially be used for programming studies to different these target population…” (top of 2nd column of p. 4656). Even assuming the declaration established that the applicants used the claimed composition for reprogramming cancer cells, the use is not a required part of the claim as recited. Therefore, these arguments do not distinguish if over the prior art. Furthermore, the arguments regarding the strong anti-cancer effects throughout the body with OS-001 is not persuasive because the data is not commensurate in scope with the claims. OS-001 is a PBAE NP encapsulating DNA encoding 4-IBB: and IL-12. However, the instant claims are broadly drawn to a composition comprising at least one first genetic element that encodes a signal 2 protein and a second genetic element that encodes a signal 3 protein encapsulated in a nanoparticle comprising formula I (see MPEP 2145). For the reasons above, the Declaration is not persuasive to overcome the rejections of record.
Double Patenting-Maintained
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.
The rejection of claims 1-9, 14-16, 25-26 and 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 58-69 of copending Application No. 18/741,056 (reference application) in view of Quinones-Hinojosa et al. (US 2017/0216363) in view of Riley et al. (WO2005/118788) is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other.
The copending Application claims a PBAE that meets the limitations of claim 1 and a nanoparticle comprising the formula and a nucleic acid (claims 58-65). The copending Application claims the method for delivering the nucleic acid to the cell for treating GBM and other cancers.
The copending Application does not teach the nucleic acid is a signal 1, 2 and 3 protein. However, the teachings of Quinones-Hinojosa et al. and Riley et al. cure this deficiency (the teachings are presented above in detail).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the nanoparticle of the copending application with the a signal 3 protein as taught by Quinones-Hinojosa et al. to further include a genetic element encoding a signal 2 protein (e.g. CD80, CD86, 4-1BBL, OX40L) and signal 1 proteins (e.g. MHC class I) as taught by Riley et al. because Riley et al. each aAPCs that co-express signal 1, signal 2 and signal 3 proteins to stimulate antigen presenting T-cell responses, including T cell activation and proliferation. Given that Quinones-Hinojosa et al. already teaches a PBAE nanoparticle systems suitable for encapsulating genetic material for therapeutic use, particularly in cancer therapy, it would have been routine and a predictable design choice for a skilled artisan to co-deliver the genetic elements encoding all three types of immune signals in order to recapitulate the full spectrum of T cell activation within a single delivery vehicle. A person of ordinary skill in the art would understand that delivering the signal 1, 2 and 3 components from a single nanoparticle would ensure delivery of the signals to the same immune cell population. There is a reasonable expectation of success given that the combination is a predictable use of known immune stimulatory elements in a known delivery system and Quinones-Hinojosa et al. teach treatment of brain tumors.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejection of claims 1-9, 14-16 and 25-30 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 58-69 of copending Application No. 18/741,056 (reference application) in view of Quinones-Hinojosa et al. (US 2017/0216363), Riley et al. (WO2005/118788) and Hardcastle et al. is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other.
The copending Application does not teach the composition in combination with an anti-PD-1 antibody. However, the teachings of Hardcastle et al. cure this deficiency (presented in detail above).
With respect to claim 27, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to combine an anti-PD1 antibody in the nanoparticle comprising PBAE as taught by the copending application, Quinones-Hinojosa et al. and Riley et al. A person of ordinary skill would look to the teachings of Quinones-Hinojosa et al. and have a motivation to include anti-PD1 as taught by Hardcastle et al. because they are both for treating the same condition: brain tumors. 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.” Furthermore, a person of ordinary skill in the art would be motivated to use anti-PD1 in combination with the composition of Quinones-Hinojosa et al. and Riley et al. because the teachings of Hardcastle et al. suggest combining therapies can improve therapeutic output. A reasonable expectation of success is expected given that each component are potential treatments for brain tumors. Moreover, there is a reasonable expectation of success given incorporating an anti-PD1 antibody in the nanoparticle formulation would potentiate the immune response against the tumor, leading to improved efficacy.
Response to Arguments
Applicant's arguments filed 11/7/25 have been fully considered but they are not persuasive. Applicants argue that the ‘056 application neither teaches or suggest PBAE compositions suitable for reprogramming in vivo one or more cancer cells into one or more tAPCs by non-virally introducing one or more nucleic acids into the cancer cells.
This argument was considered but is not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e. reprogramming cancer cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In the instant case, the claims are product claims and not methods of use. The rejection is maintained.
The rejection of claims 1-9, 14-16, 25-26 and 29-30 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-13, 15, 17-19, 21-22, 40-41, 44-48, 50-51 of copending Application No. 18/274,133 (reference application) in view of Quinones-Hinojosa et al. (US 2017/0216363) in view of Riley et al. (WO2005/118788) is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other.
The copending Application claims a PBAE that meets the limitations of claims 13-15 and a nanoparticle comprising the formula and a nucleic acid. The copending Application claims the method for treating glioblastoma and other cancers.
The copending Application does not teach the nucleic acid is a signal 1, 2 and 3 protein. However, the teachings of Quinones-Hinojosa et al. and Riley et al. cure this deficiency (the teachings are presented above in detail).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the nanoparticle of the copending application with the a signal 3 protein as taught by Quinones-Hinojosa et al. to further include a genetic element encoding a signal 2 protein (e.g. CD80, CD86, 4-1BBL, OX40L) and signal 1 proteins (e.g. MHC class I) as taught by Riley et al. because Riley et al. each aAPCs that co-express signal 1, signal 2 and signal 3 proteins to stimulate antigen presenting T-cell responses, including T cell activation and proliferation. Given that Quinones-Hinojosa et al. already teaches a PBAE nanoparticle systems suitable for encapsulating genetic material for therapeutic use, particularly in cancer therapy, it would have been routine and a predictable design choice for a skilled artisan to co-deliver the genetic elements encoding all three types of immune signals in order to recapitulate the full spectrum of T cell activation within a single delivery vehicle. A person of ordinary skill in the art would understand that delivering the signal 1, 2 and 3 components from a single nanoparticle would ensure delivery of the signals to the same immune cell population. There is a reasonable expectation of success given that the combination is a predictable use of known immune stimulatory elements in a known delivery system and Quinones-Hinojosa et al. teach treatment of brain tumors.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejection of claims 1-9, 14-16 and 25-30 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-13, 15, 17-19, 21-22, 40-41, 44-48, 50-51 of copending Application No. 18/274,133 (reference application) in view of Quinones-Hinojosa et al. (US 2017/0216363), Riley et al. (WO2005/118788) and Hardcastle et al. is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other.
The copending Application does not teach the composition in combination with an anti-PD-1 antibody. However, the teachings of Hardcastle et al. cure this deficiency (presented in detail above).
With respect to claim 27, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to combine an anti-PD1 antibody in the nanoparticle comprising PBAE as taught by the copending application, Quinones-Hinojosa et al. and Riley et al. A person of ordinary skill would look to the teachings of Quinones-Hinojosa et al. and have a motivation to include anti-PD1 as taught by Hardcastle et al. because they are both for treating the same condition: brain tumors. 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.” Furthermore, a person of ordinary skill in the art would be motivated to use anti-PD1 in combination with the composition of Quinones-Hinojosa et al. and Riley et al. because the teachings of Hardcastle et al. suggest combining therapies can improve therapeutic output. A reasonable expectation of success is expected given that each component are potential treatments for brain tumors. Moreover, there is a reasonable expectation of success given incorporating an anti-PD1 antibody in the nanoparticle formulation would potentiate the immune response against the tumor, leading to improved efficacy.
Response to Arguments
Applicant's arguments filed 11/7/25 have been fully considered but they are not persuasive. Applicants argue that the instant application has he earlier filing date and should be withdrawn according to MPEP 1490.
This argument is not persuasive as the double patenting rejection is not the only remaining rejection of record. The rejection is maintained for the reasons above.
The rejection of claims 1-9, 14-16, 25-26 and 29-30 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of USPN 12,059,476 is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other.
The USPN claims a particle comprising PBAE that meets the limitations of claims 13-16. The USPN claims the particle comprises MHC class I or II, wherein the particle further comprises CD80 and CD86, wherein the particle comprises an immune checkpoint blocking molecule such as anti-PD1, wherein the particle encapsulates a cytokine.
The USPN does not claim a signal 3 protein or the MHC class I, CD80 or CD86 are encapsulated in the nanoparticle. However, the teachings of Quinones-Hinojosa et al. cure this deficiency (the teachings are presented above in detail).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the nanoparticle of the USPN with the signal 3 protein as taught by Quinones-Hinojosa et al. Given that Quinones-Hinojosa et al. already teaches a PBAE nanoparticle systems suitable for encapsulating genetic material for therapeutic use, particularly in cancer therapy, it would have been routine and a predictable design choice for a skilled artisan to co-deliver the genetic elements encoding all three types of immune signals in order to recapitulate the full spectrum of T cell activation within a single delivery vehicle. A person of ordinary skill in the art would understand that delivering the signal 1, 2 and 3 components from a single nanoparticle would ensure delivery of the signals to the same immune cell population. There is a reasonable expectation of success given that the combination is a predictable use of known immune stimulatory elements in a known delivery system and Quinones-Hinojosa et al. teach treatment of brain tumors.
Response to Arguments
Applicant's arguments filed 11/7/25 have been fully considered but they are not persuasive. Applicants argue that the USPN neither teaches or suggest PBAE compositions suitable for reprogramming in vivo one or more cancer cells into one or more tAPCs by non-virally introducing one or more nucleic acids into the cancer cells.
This argument was considered but is not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e. reprogramming cancer cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In the instant case, the claims are product claims and not methods of use. The rejection is maintained.
The rejection of claims 1-9, 14-16, 25-30 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application 17/602,932 in view of Quinones-Hinojosa et al., Bhise et al. and Hardcastle et al. is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other.
The copending Application claims a particle comprising PBAE. The copending Application claims the particle comprises a signal 1, 2 and 3 protein on the surface, wherein the signal 1 is MHC class I, wherein the signal 2 is 4-1BBL, CD80, CD86 and OX40L, wherein the signal 3 is an interleukin or cytokine (claims 1-9). The copending application claims the nanoparticle is 50 nm to 1000 nm (claim 12). The copending application does not teach the PBAE of claims 13-16 or the use of an immune check point inhibitor. However, the teachings of Quinones-Hinojosa et al., Bhise et al. and Hardcastle et al. cure this deficiency.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the nanoparticle of the copending application by encapsulating the signal proteins given that Quinones-Hinojosa et al. already teaches a PBAE nanoparticle systems suitable for encapsulating genetic material for therapeutic use, particularly in cancer therapy, it would have been routine and a predictable design choice for a skilled artisan to co-deliver the genetic elements encoding all three types of immune signals in order to recapitulate the full spectrum of T cell activation within a single delivery vehicle. A person of ordinary skill in the art would understand that delivering the signal 1, 2 and 3 components from a single nanoparticle would ensure delivery of the signals to the same immune cell population. There is a reasonable expectation of success given that the combination is a predictable use of known immune stimulatory elements in a known delivery system and Quinones-Hinojosa et al. teach treatment of brain tumors.
It would have been obvious to a person of ordinary skill in the art to pick specific monomeric components used in the claimed PBAE monomers for nanoparticle formation comprising the genetic elements of the copending application and Quinones-Hinojosa et al. A person of ordinary skill in the art would look to the teachings of Bhise et al. disclosure of a structure function relationship analysis of various PBAE formulations and have a motivation to optimize the combination in order to optimize cellular uptake of the nanoparticles. There is a reasonable expectation of success given that Bhise et al. test multiple combination of monomers at different ratios.
With respect to claim 27, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to combine an anti-PD1 antibody in the nanoparticle comprising PBAE as taught by the copending application, Quinones-Hinojosa et al. and Bhise et al. A person of ordinary skill would look to the teachings Quinones-Hinojosa et al. and have a motivation to include anti-PD1 as taught by Hardcastle et al. because they are both for treating the same condition: brain tumors. 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.” Furthermore, a person of ordinary skill in the art would be motivated to use anti-PD1 in combination with the composition of Quinones-Hinojosa et al. and Riley et al. because the teachings of Hardcastle et al. suggest combining therapies can improve therapeutic output. A reasonable expectation of success is expected given that each component are potential treatments for brain tumors. Moreover, there is a reasonable expectation of success given incorporating an anti-PD1 antibody in the nanoparticle formulation would potentiate the immune response against the tumor, leading to improved efficacy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 11/7/25 have been fully considered but they are not persuasive. Applicants argue that the instant application has he earlier filing date and should be withdrawn according to MPEP 1490.
This argument is not persuasive as the double patenting rejection is not the only remaining rejection of record. The rejection is maintained for the reasons above.
Claims 1-9, 14-16 and 25-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-51 of copending Application 19/455,150 in view of Bhise et al. Although the claims at issue are not identical, they are not patentably distinct from each other. This is a NEW rejection due to filing of a new application (1/21/26) after mailing of the non-final rejection (5/8/25).
The copending application claims a composition comprising a nucleic acid encoding a signal 2 polypeptide and second nucleotide encoding a signal 3 polypeptide, wherein the signal 2 polypeptide is a cell surface bound protein that regulates immune cells, wherein the signal 3 polypeptide is a secreted protein that regulates immune cells, wherein the signal 3 polypeptide comprises a cytokine, wherein the cytokine is an interleukin, wherein the first nucleotide encodes 4-IBBL, CD28, CD80, CD86, OX40L or GITRL, wherein the second nucleic acid encodes TGF-beta 1…or IFN-beta, wherein the biomaterial comprises a cationic biodegradable polymer, wherein the polymer is PBAE, is in the form of nanoparticles. The copending application also claims a method for treating cancer, including brain cancer and use of the composition in combination with one or more checkpoint inhibitors, wherein the checkpoint inhibitors is an ant-PD-1 antibody (claims 1-51).
The copending application does not teach the PBAE of formula 1. However, the teachings of Bhise et al. cure this deficiency.
The teachings of Bhise et al. are presented above in detail.
It would have been obvious to a person of ordinary skill in the art to pick specific monomeric components used in the claimed PBAE monomers for nanoparticle formation comprising the genetic elements of copending application. A person of ordinary skill in the art would look to the teachings of Bhise et al. disclosure of a structure function relationship analysis of various PBAE formulations and have a motivation to optimize the combination in order to optimize cellular uptake of the nanoparticles. There is a reasonable expectation of success given that Bhise et al. test multiple combination of monomers at different ratios.
Conclusion
No claims are allowed.
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/TARA L MARTINEZ/Examiner, Art Unit 1654