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 .
This action is in response to the amendment filed 07/24/2026, in which claims 1, 7, 8, 15 and 19 were amended, claims 2 and 9 are canceled and claims 3-6, 10-14, 16-18 and 20 were previously presented. Claims 1, 3-8 and 10-20 are currently pending.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the
reasons that follow. Any rejection and objections not reiterated in this action have been
withdrawn. This action is FINAL.
Nucleotide and/or Amino Acid Sequence Disclosures
The previous objection to the sequence disclosure has been withdrawnin view of Applicant’s amendments to the claims filed on 07/24/2026.
Response to Amendment - Claim Rejections - 35 USC § 112
The previous rejection of claims 1 and 3-20 under 35 U.S.C. 112(a) for written
description has been withdrawn in view of Applicant’s amendments to the claims filed on 07/24/2026.
The previous rejection of claims 1 and 3-20 under 35 U.S.C. 112(a) for scope of enablement has been withdrawn in view of Applicant’s amendments to the claims filed on 07/24/2026.
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.
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 1, 3-8 and 10-20 are rejected under 35 U.S.C. 103 as being unpatentable by Levitzki et al (WO 2015/173824 A1, cited as reference FP2 ono the IDS filed 5/12/2023) in view of Langut et al (Oncotarget. 2017 Apr 11;8(15):24046-24062, available online February 25, 2017). This is a Rejection made in a prior Office Action mailed on 01/27/2026 and re-written to address the amendments to the claims filed on 07/24/2026.
Levitzki teaches the treatment of a patient with prostate cancer by the administration of a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen [0008 and 0039]. Levitzki teaches the dsRNA is polyinosinic-polycytidylic acid double stranded RNA (poly I:C), the polymeric conjugate consists of LPEI covalently linked to one PEG moiety (LPEI-PEG 1:1) or to three PEG moieties (LPEI-PEG 1:3), and the cancer antigen is prostate surface membrane antigen (PSMA) [0041]. Levitzki teaches the prostate surface membrane antigen (PSMA) is overexpressed metastatic prostate cancer [00125]. Levitzki teaches the targeting moiety is HOOC(CH2)2-CH(COOH)-NHCO-NH-CH(COOH)-(CH 2)2-CO- (DUPA residue), and the polymeric conjugate is of the formula (vii) [0050-0051]. Below shows the structure of formula (vii):
PNG
media_image1.png
232
359
media_image1.png
Greyscale
PNG
media_image2.png
233
486
media_image2.png
Greyscale
(Page 11-12).
Levitzki does not teach the specific treatment of castration resistant prostate cancer.
Langut teaches using synthetic dsRNA polyIC (polyinosinic/polycytidylic acid) for the treatment of androgen-resistant prostate cancer where the polyIC is complexed to a delivery vector capable of targeting the overexpressed prostate specific membrane antigen present on the surface of prostate cancer cells (Page 24046, Abstract and Page 24055, Column 2, Paragraph 3). Langut teaches that PSMA is the target of choice for targeted treatment of prostate cancer in general and castration resistant prostate cancer (CPRC) tumors in particular (Page 24054, Column 1, Paragraph 2). Langut teaches that the targeted delivery of polyIC directly kills cells that overexpress PSMA and activates direct and immune-cell-mediated bystander effects to eradicate heterogenous tumors (Page 24054, Column 1, Paragraph 2). Langut teaches the use of polyIC for the treatment of androgen-resistant prostate cancer (also referred to as castration-resistant prostate cancer) due to the high effectiveness and low toxicity and for preferred use for patient that are immune compromised (Page 24055, Column 2, Paragraph 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Levitzki to specifically include the treatment of castration resistant prostate cancer as the type of prostate cancer treated, because Levitzki teaches the treatment of prostate cancer with a complex comprising polyIC, and Langut specifically teaches the suitability of polyIC for the treatment of castration resistant prostate cancer. Levitzki teaches it is within the ordinary skill in the art to use a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen and Langut teaches the use of polyIC for the successful treatment of castration-resistant prostate cancer. Therefore, one would have had a reasonable expectation of success in using polyIC within the polyplex composition for the treatment of CRPC.
Regarding claim 3, Levitzki teaches the dsRNA is polyinosinic-polycytidylic acid double
stranded RNA (poly I:C), the polymeric conjugate consists of LPEI covalently linked to one
PEG moiety (LPEI-PEG 1:1) or to three PEG moieties (LPEI-PEG 1:3), and the cancer
antigen is prostate surface membrane antigen (PSMA) [0041].
Regarding claims 4-6, Levitzki teaches the use of the peptide moiety is -(NH-(CH2)7-CO)-Phe-GlyTrp-Trp-Gly-Cys- (SEQ ID NO: 2) or -(NH-(CH2)7-CO)-Phe-Phe-(NH-CH2-CH(NH2)-CO) Asp-Cys- (SEQ ID NO: 3) [0049]. In the instant case, instant SEQ ID NO: 1 is 100% identical to SEQ ID NO: 2 of Levitzki as well as instant SEQ ID NO: 2 is 100% identical to SEQ ID NO: 3 of Levitzki.
Regarding claim 7, Levitzki teaches the polymeric conjugate is -(NH-(CH2)7-CO)-Phe-Gly-Trp-Trp-Gly-Cys-PEG2k-LPEI and linked to a targeting moiety [0050].
Regarding claim 8, Levitzki teaches the targeting moiety is HOOC(CH2)2-CH(COOH)-NHCO-NH-CH(COOH)-(CH 2)2-CO- (DUPA residue), and the polymeric conjugate is of the formula (vii) [0050-0051]. Below shows the structure of formula (vii):
PNG
media_image1.png
232
359
media_image1.png
Greyscale
PNG
media_image2.png
233
486
media_image2.png
Greyscale
(Page 11-12).
Regarding claims 10 and 16, Levitzki teaches the prostate surface membrane antigen (PSMA) is overexpressed metastatic prostate cancer [00125].
Levitzki does not teach the specific treatment of castration resistant prostate cancer.
Langut teaches using synthetic dsRNA polyIC (polyinosinic/polycytidylic acid) for the treatment of androgen-resistant prostate cancer where the polyIC is complexed to a delivery vector capable of targeting the overexpressed prostate specific membrane antigen present on the surface of prostate cancer cells (Page 24046, Abstract and Page 24055, Column 2, Paragraph 3). Langut teaches that PSMA is the target of choice for targeted treatment of prostate cancer in general and castration resistant prostate cancer (CPRC) tumors in particular (Page 24054, Column 1, Paragraph 2). Langut teaches that the targeted delivery of polyIC directly kills cells that overexpress PSMA and activates direct and immune-cell-mediated bystander effects to eradicate heterogenous tumors (Page 24054, Column 1, Paragraph 2). Langut teaches the use of polyIC for the treatment of androgen-resistant prostate cancer (also referred to as castration-resistant prostate cancer) due to the high effectiveness and low toxicity and for preferred use for patient that are immune compromised (Page 24055, Column 2, Paragraph 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Levitzki to specifically include the treatment of castration resistant prostate cancer as the type of prostate cancer treated, because Levitzki teaches the treatment of prostate cancer with a complex comprising polyIC, and Langut specifically teaches the suitability of polyIC for the treatment of castration resistant prostate cancer. Levitzki teaches it is within the ordinary skill in the art to use a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen and Langut teaches the use of polyIC for the successful treatment of castration-resistant prostate cancer. Therefore, one would have had a reasonable expectation of success in using polyIC within the polyplex composition for the treatment of CRPC.
Regarding claims 11, 12 and 17, the term “androgen receptor (AR) independent CRPC” is defined as neuroendocrine prostate cancer as taught in the instant specification (Page 8, line 34 bridging Page 9, line 1). The instant specification defines AR independent CRPC as resistant (i. e. sensitive) to androgen treatment (Page 9, Lines 5-6).
Levitzki does not teach the CRPC is androgen receptor (AR) independent CRPC such as neuroendocrine prostate cancer.
Langut teaches using synthetic dsRNA polyIC (polyinosinic/polycytidylic acid) for the treatment of androgen-resistant prostate cancer where the polyIC is complexed to a delivery vector capable of targeting the overexpressed prostate specific membrane antigen present on the surface of prostate cancer cells (Page 24046, Abstract and Page 24055, Column 2, Paragraph 3). Langut teaches that PSMA is the target of choice for targeted treatment of prostate cancer in general and castration resistant prostate cancer (CPRC) tumors in particular (Page 24054, Column 1, Paragraph 2). Langut teaches that the targeted delivery of polyIC directly kills cells that overexpress PSMA and activates direct and immune-cell-mediated bystander effects to eradicate heterogenous tumors (Page 24054, Column 1, Paragraph 2). Langut teaches the use of polyIC for the treatment of androgen-resistant prostate cancer (also referred to as castration-resistant prostate cancer) due to the high effectiveness and low toxicity and for preferred use for patient that are immune compromised (Page 24055, Column 2, Paragraph 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Levitzki to specifically include the treatment of castration resistant prostate cancer as the type of prostate cancer treated, because Levitzki teaches the treatment of prostate cancer with a complex comprising polyIC, and Langut specifically teaches the suitability of polyIC for the treatment of castration resistant prostate cancer. Levitzki teaches it is within the ordinary skill in the art to use a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen and Langut teaches the use of polyIC for the successful treatment of castration-resistant prostate cancer. Therefore, one would have had a reasonable expectation of success in using polyIC within the polyplex composition for the treatment of CRPC.
Regarding claims 13 and 14, Levitzki teaches the immune cells are tumor-infiltrating T-cells (T-TILs), tumor specific engineered T-cells, or peripheral blood mononuclear cells (PBMCs) [0065].
Regarding claim 15, Levitzki teaches the treatment of a patient with prostate cancer by the administration of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the polyplex composition comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen [0009 and 0039]. Levitzki teaches the dsRNA is polyinosinic-polycytidylic acid double stranded RNA (poly I:C), the polymeric conjugate consists of LPEI covalently linked to one PEG moiety (LPEI-PEG 1:1) or to three PEG moieties (LPEI-PEG 1:3), and the cancer antigen is prostate surface membrane antigen (PSMA) [0041]. Levitzki teaches the targeting moiety is HOOC(CH2)2-CH(COOH)-NHCO-NH-CH(COOH)-(CH 2)2-CO- (DUPA residue), and the polymeric conjugate is of the formula (vii) [0050-0051]. Below shows the structure of formula (vii):
PNG
media_image1.png
232
359
media_image1.png
Greyscale
PNG
media_image2.png
233
486
media_image2.png
Greyscale
(Page 11-12).
Levitzki does not teach the specific treatment of castration resistant prostate cancer.
Langut teaches using synthetic dsRNA polyIC (polyinosinic/polycytidylic acid) for the treatment of androgen-resistant prostate cancer where the polyIC is complexed to a delivery vector capable of targeting the overexpressed prostate specific membrane antigen present on the surface of prostate cancer cells (Page 24046, Abstract and Page 24055, Column 2, Paragraph 3). Langut teaches that PSMA is the target of choice for targeted treatment of prostate cancer in general and castration resistant prostate cancer (CPRC) tumors in particular (Page 24054, Column 1, Paragraph 2). Langut teaches that the targeted delivery of polyIC directly kills cells that overexpress PSMA and activates direct and immune-cell-mediated bystander effects to eradicate heterogenous tumors (Page 24054, Column 1, Paragraph 2). Langut teaches the use of polyIC for the treatment of androgen-resistant prostate cancer (also referred to as castration-resistant prostate cancer) due to the high effectiveness and low toxicity and for preferred use for patient that are immune compromised (Page 24055, Column 2, Paragraph 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Levitzki to specifically include the treatment of castration resistant prostate cancer as the type of prostate cancer treated, because Levitzki teaches the treatment of prostate cancer with a complex comprising polyIC, and Langut specifically teaches the suitability of polyIC for the treatment of castration resistant prostate cancer. Levitzki teaches it is within the ordinary skill in the art to use a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen and Langut teaches the use of polyIC for the successful treatment of castration-resistant prostate cancer. Therefore, one would have had a reasonable expectation of success in using polyIC within the polyplex composition for the treatment of CRPC.
Regarding claim 18, Levitzki teaches the use of the peptide moiety is -(NH-(CH2)7-CO)-Phe-GlyTrp-Trp-Gly-Cys- (SEQ ID NO: 2) [0049]. In the instant case, instant SEQ ID NO: 1 is 100% identical to SEQ ID NO: 2 of Levitzki.
Regarding claim 19, Levitzki teaches the polymeric conjugate is -(NH-(CH2)7-CO)-Phe-Gly-Trp-Trp-Gly-Cys-PEG2k-LPEI and linked to a targeting moiety [0050].
Regarding claim 20, Levitzki teaches the polymeric conjugate is a diconjugate of the formula (i), linked to the targeting moiety/moieties [0050]. Below shows the structure of formula (i):
PNG
media_image3.png
255
461
media_image3.png
Greyscale
(Page 10)
Below shows the structure of the peptide moiety attached to the structure of formula (i) at the sulfur bond (referenced in Levitzki as R7):
PNG
media_image4.png
242
564
media_image4.png
Greyscale
(Page 12)
Claims 1, 3-8 and 10-20 are rejected under 35 U.S.C. 103 as being unpatentable by Levitzki et al (WO 2015/173824 A1) in view of Palchetti et al (RSC Adv., 2013, 3, 24597-24604). This is a Rejection made in a prior Office Action mailed on 01/27/2026 and re-written to address the amendments to the claims filed on 07/24/2026.
Regarding claim 1, Levitzki teaches the treatment of a patient with prostate cancer by the administration of a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen [0008 and 0039]. Levitzki teaches the dsRNA is polyinosinic-polycytidylic acid double stranded RNA (poly I:C), the polymeric conjugate consists of LPEI covalently linked to one PEG moiety (LPEI-PEG 1:1) or to three PEG moieties (LPEI-PEG 1:3), and the cancer antigen is prostate surface membrane antigen (PSMA) [0041]. Levitzki teaches the prostate surface membrane antigen (PSMA) is overexpressed metastatic prostate cancer [00125]. Levitzki teaches the targeting moiety is HOOC(CH2)2-CH(COOH)-NHCO-NH-CH(COOH)-(CH 2)2-CO- (DUPA residue), and the polymeric conjugate is of the formula (vii) [0050-0051]. Below shows the structure of formula (vii):
PNG
media_image1.png
232
359
media_image1.png
Greyscale
PNG
media_image2.png
233
486
media_image2.png
Greyscale
(Page 11-12).
Levitzki does not teach the specific treatment of castration resistant prostate cancer.
Palchetti teaches that previously polyI:C has shown significant apoptosis effects in androgen-dependent prostate cancer, this is prostate cancer that is sensitive to androgen treatments, therefore polyI:C is being looked at for the more aggressive prostate cancer known as androgen-independent prostate cancer (Page 24598, Column 1). Palchetti teaches that the use of polyI:C, a synthetic dsRNA, was more efficient in inducing apoptosis in aggressive androgen-independent prostate cancer cells compared to other free drugs (Page 24600, Column 2 and Page 24602, Column 1), thereby showing a strong reduction of castration-resistant prostate cancer cell viability (Page 24600, Column 2 and Page 24602, Column 1). Palchetti teaches that the observed results were in good agreement with those of other researchers who have reported the induction of apoptosis by poly(I:C) and cationic liposomes in murine melanoma and hepatoma cells (Page 24600, Column 2 and Page 24602, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Levitzki to specifically include the treatment of castration resistant prostate cancer as the type of prostate cancer treated, because Levitzki teaches the treatment of prostate cancer with a complex comprising polyIC, and Palchetti specifically teaches the suitability of polyIC for the treatment of castration resistant prostate cancer. Levitzki teaches it is within the ordinary skill in the art to use a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen and Palchetti teaches the use of polyIC to for the successful treatment of castration-resistant prostate cancer among other types of cancers. Therefore, one would have had a reasonable expectation of success in using polyIC within the polyplex composition for the treatment of CRPC.
Regarding claim 3, Levitzki teaches the dsRNA is polyinosinic-polycytidylic acid double
stranded RNA (poly I:C), the polymeric conjugate consists of LPEI covalently linked to one
PEG moiety (LPEI-PEG 1:1) or to three PEG moieties (LPEI-PEG 1:3), and the cancer
antigen is prostate surface membrane antigen (PSMA) [0041].
Regarding claims 4-6, Levitzki teaches the use of the peptide moiety is -(NH-(CH2)7-CO)-Phe-GlyTrp-Trp-Gly-Cys- (SEQ ID NO: 2) or -(NH-(CH2)7-CO)-Phe-Phe-(NH-CH2-CH(NH2)-CO) Asp-Cys- (SEQ ID NO: 3) [0049]. In the instant case, instant SEQ ID NO: 1 is 100% identical to SEQ ID NO: 2 of Levitzki as well as instant SEQ ID NO: 2 is 100% identical to SEQ ID NO: 3 of Levitzki.
Regarding claim 7, Levitzki teaches the polymeric conjugate is -(NH-(CH2)7-CO)-Phe-Gly-Trp-Trp-Gly-Cys-PEG2k-LPEI and linked to a targeting moiety [0050].
Regarding claim 8, Levitzki teaches the targeting moiety is HOOC(CH2)2-CH(COOH)-NHCO-NH-CH(COOH)-(CH 2)2-CO- (DUPA residue), and the polymeric conjugate is of the formula (vii) [0050-0051]. Below shows the structure of formula (vii):
PNG
media_image1.png
232
359
media_image1.png
Greyscale
PNG
media_image2.png
233
486
media_image2.png
Greyscale
(Page 11-12)
Regarding claims 10 and 16, Levitzki teaches the prostate surface membrane antigen (PSMA) is overexpressed metastatic prostate cancer [00125].
Levitzki does not teach the specific treatment of castration resistant prostate cancer.
Palchetti teaches that previously polyI:C has shown significant apoptosis effects in androgen-dependent prostate cancer, this is prostate cancer that is sensitive to androgen treatments, therefore polyI:C is being looked at for the more aggressive prostate cancer known as androgen-independent prostate cancer (Page 24598, Column 1). Palchetti teaches that the use of polyI:C, a synthetic dsRNA, was more efficient in inducing apoptosis in aggressive androgen-independent prostate cancer cells compared to other free drugs (Page 24600, Column 2 and Page 24602, Column 1), thereby showing a strong reduction of castration-resistant prostate cancer cell viability (Page 24600, Column 2 and Page 24602, Column 1). Palchetti teaches that the observed results were in good agreement with those of other researchers who have reported the induction of apoptosis by poly(I:C) and cationic liposomes in murine melanoma and hepatoma cells (Page 24600, Column 2 and Page 24602, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Levitzki to specifically include the treatment of castration resistant prostate cancer as the type of prostate cancer treated, because Levitzki teaches the treatment of prostate cancer with a complex comprising polyIC, and Palchetti specifically teaches the suitability of polyIC for the treatment of castration resistant prostate cancer. Levitzki teaches it is within the ordinary skill in the art to use a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen and Palchetti teaches the use of polyIC to for the successful treatment of castration-resistant prostate cancer among other types of cancers. Therefore, one would have had a reasonable expectation of success in using polyIC within the polyplex composition for the treatment of CRPC.
Regarding claims 11, 12 and 17, the term “androgen receptor (AR) independent CRPC” is defined as neuroendocrine prostate cancer as taught in the instant specification (Page 8, line 34 bridging Page 9, line 1). The instant specification defines AR independent CRPC as resistant (i. e. sensitive) to androgen treatment (Page 9, Lines 5-6).
Levitzki does not teach the CRPC is androgen receptor (AR) independent CRPC such as neuroendocrine prostate cancer.
Palchetti teaches that previously polyI:C has shown significant apoptosis effects in androgen-dependent prostate cancer, this is prostate cancer that is sensitive to androgen treatments, therefore polyI:C is being looked at for the more aggressive prostate cancer known as androgen-independent prostate cancer (Page 24598, Column 1). Palchetti teaches that the use of polyI:C, a synthetic dsRNA, was more efficient in inducing apoptosis in aggressive androgen-independent prostate cancer cells compared to other free drugs (Page 24600, Column 2 and Page 24602, Column 1), thereby showing a strong reduction of castration-resistant prostate cancer cell viability (Page 24600, Column 2 and Page 24602, Column 1). Palchetti teaches that the observed results were in good agreement with those of other researchers who have reported the induction of apoptosis by poly(I:C) and cationic liposomes in murine melanoma and hepatoma cells (Page 24600, Column 2 and Page 24602, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Levitzki to specifically include the treatment of castration resistant prostate cancer as the type of prostate cancer treated, because Levitzki teaches the treatment of prostate cancer with a complex comprising polyIC, and Palchetti specifically teaches the suitability of polyIC for the treatment of castration resistant prostate cancer. Levitzki teaches it is within the ordinary skill in the art to use a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen and Palchetti teaches the use of polyIC to for the successful treatment of castration-resistant prostate cancer among other types of cancers. Therefore, one would have had a reasonable expectation of success in using polyIC within the polyplex composition for the treatment of CRPC.
Regarding claims 13 and 14, Levitzki teaches the immune cells are tumor-infiltrating T-cells (T-TILs), tumor specific engineered T-cells, or peripheral blood mononuclear cells (PBMCs) [0065].
Regarding claim 15, Levitzki teaches the treatment of a patient with prostate cancer by the administration of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the polyplex composition comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen [0009 and 0039]. Levitzki teaches the dsRNA is polyinosinic-polycytidylic acid double stranded RNA (poly I:C), the polymeric conjugate consists of LPEI covalently linked to one PEG moiety (LPEI-PEG 1:1) or to three PEG moieties (LPEI-PEG 1:3), and the cancer antigen is prostate surface membrane antigen (PSMA) [0041]. Levitzki teaches the targeting moiety is HOOC(CH2)2-CH(COOH)-NHCO-NH-CH(COOH)-(CH 2)2-CO- (DUPA residue), and the polymeric conjugate is of the formula (vii) [0050-0051]. Below shows the structure of formula (vii):
PNG
media_image1.png
232
359
media_image1.png
Greyscale
PNG
media_image2.png
233
486
media_image2.png
Greyscale
(Page 11-12).
Levitzki does not teach the specific treatment of castration resistant prostate cancer.
Palchetti teaches that previously polyI:C has shown significant apoptosis effects in androgen-dependent prostate cancer, this is prostate cancer that is sensitive to androgen treatments, therefore polyI:C is being looked at for the more aggressive prostate cancer known as androgen-independent prostate cancer (Page 24598, Column 1). Palchetti teaches that the use of polyI:C, a synthetic dsRNA, was more efficient in inducing apoptosis in aggressive androgen-independent prostate cancer cells compared to other free drugs (Page 24600, Column 2 and Page 24602, Column 1), thereby showing a strong reduction of castration-resistant prostate cancer cell viability (Page 24600, Column 2 and Page 24602, Column 1). Palchetti teaches that the observed results were in good agreement with those of other researchers who have reported the induction of apoptosis by poly(I:C) and cationic liposomes in murine melanoma and hepatoma cells (Page 24600, Column 2 and Page 24602, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Levitzki to specifically include the treatment of castration resistant prostate cancer as the type of prostate cancer treated, because Levitzki teaches the treatment of prostate cancer with a complex comprising polyIC, and Palchetti specifically teaches the suitability of polyIC for the treatment of castration resistant prostate cancer. Levitzki teaches it is within the ordinary skill in the art to use a polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI) covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen and Palchetti teaches the use of polyIC to for the successful treatment of castration-resistant prostate cancer among other types of cancers. Therefore, one would have had a reasonable expectation of success in using polyIC within the polyplex composition for the treatment of CRPC.
Regarding claim 18, Levitzki teaches the use of the peptide moiety is -(NH-(CH2)7-CO)-Phe-GlyTrp-Trp-Gly-Cys- (SEQ ID NO: 2) [0049]. In the instant case, instant SEQ ID NO: 1 is 100% identical to SEQ ID NO: 2 of Levitzki.
Regarding claim 19, Levitzki teaches the polymeric conjugate is -(NH-(CH2)7-CO)-Phe-Gly-Trp-Trp-Gly-Cys-PEG2k-LPEI and linked to a targeting moiety [0050].
Regarding claim 20, Levitzki teaches the polymeric conjugate is a diconjugate of the formula (i), linked to the targeting moiety/moieties [0050]. Below shows the structure of formula (i):
PNG
media_image3.png
255
461
media_image3.png
Greyscale
(Page 10)
Below shows the structure of the peptide moiety attached to the structure of formula (i) at the sulfur bond (referenced in Levitzki as R7):
PNG
media_image4.png
242
564
media_image4.png
Greyscale
(Page 12).
Response to Arguments - Claim Rejections - 35 USC § 103
The previous rejection of claims 1, 3-8 and 10-20 under 35 U.S.C. 103 over Levitzki et al (WO 2015/173824 A1, cited as reference FP2 ono the IDS filed 5/12/2023) in view of Langut et al (Oncotarget. 2017 Apr 11;8(15):24046-24062, available online February 25, 2017) has been maintained in view of Applicant’s arguments filed on 07/24/2026. Applicant’s arguments have been fully considered but have not been found to be persuasive.
The previous rejection of claims 1, 3-8 and 10-20 under 35 U.S.C. 103 over Levitzki et al (WO 2015/173824 A1) in view of Palchetti et al (RSC Adv., 2013, 3, 24597-24604) has been maintained in view of Applicant’s arguments filed on 07/24/2026. Applicant’s arguments have been fully considered but have not been found to be persuasive.
Applicant argues that none of Levitzki, Langut or Palchetti, alone or in combination, discloses or suggests, the claimed methods. Therefore, Applicant requests the withdrawal of the rejection.
Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
Therefore, Applicant’s arguments are not persuasive as they do not clearly argue how the prior art references differ from the instantly claimed prior art as well as how the current claim amendments overcome the previous rejection of the claims. Thus, the rejection of the claims as established above is maintained.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention, so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1, 3-8 and 10-20 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-20 of prior U.S. Patent No. 11,679,160 B2 (herein referred to as ‘160). This is a statutory double patenting rejection.
Claims 1-20 of the ‘160 patent are identical in wording and scope to instant claim 1, 3-8 and 10-20, respectively. Claim 1 of ‘160 recites, “A method of treating castration resistant prostate cancer (CRPC) comprising administering to a patient in need thereof, an effective amount of a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI), one or more polyethylene glycol (PEG) moieties, one or more linkers and one or more targeting moieties, wherein said LPEI is covalently bound to one or more PEG moieties and each of said one or more PEG moieties is conjugated via one of said one or more linkers to one of said one or more targeting moieties, wherein each of said one or more targeting moieties is capable of binding to a cancer antigen, and wherein said cancer antigen is prostate surface membrane antigen (PSMA)”; Claim 2 of ‘160 recites “The method according to claim 1, wherein said dsRNA is polyinosinic-polycytidylic acid double stranded RNA (polyIC)”; and Claim 9 of ‘160 recites “The method according to claim 1, wherein said targeting moiety is HOOC(CH2)2-CH(COOH)-NH-CO-NH-CH(COOH)-(CH2)2-CO- (DUPA moiety)”. In comparison, Claim 1 of the instant application recites “A method of treating castration resistant prostate cancer (CRPC) comprising administering to a patient in need thereof, an effective amount of a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said dsRNA is polyinosinic-polycytidylic acid double stranded RNA (polyIC), wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI), one or more polyethylene glycol (PEG) moieties, one or more linkers and one or more targeting moieties, wherein said LPEI is covalently bound to one or more PEG moieties and each of said one or more PEG moieties is conjugated via one of said one or more linkers to one of said one or more targeting moieties, wherein said targeting moiety is HOOC(CH2)2-CH(COOH)-NH-CO-NH-CH(COOH)-(CH2)2-CO- (DUPA moiety), wherein each of said one or more targeting moieties is capable of binding to a cancer antigen, and wherein said cancer antigen is prostate surface membrane antigen (PSMA)”. The two independent claims recite the same scope and limitations and therefore claim the same invention.
Claim 3 of ‘160 recites “The method according to claim 1, wherein said LPEI is covalently bound to one PEG moiety (LPEI-PEG 1:1) or to three PEG moieties (LPEI-PEG 1:3)” whereas claim 3 of the instant application recites “The method according to claim 1, wherein said LPEI is covalently bound to one PEG moiety (LPEI-PEG 1:1) or to three PEG moieties (LPEI-PEG 1:3)”. The two dependent claims recite the same scope and limitations and therefore claim the same invention.
Claim 4 of ‘160 recites “The method according to claim 1, wherein said linker is a peptide moiety and wherein said peptide moiety consists of 3 to 7 amino acid residues” whereas claim 4 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 5 of ‘160 recites “The method according to claim 4, wherein said peptide moiety comprises the amino acid residue -(NH-(CH2)7-CO)-” whereas claim 5 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 6 of ‘160 recites “The method according to claim 5, wherein said peptide moiety is: -(NH-(CH2)7-CO)-Phe-GlyTrp-Trp-Gly-Cys- (SEQ ID NO: 1) or -(NH-(CH2)7-CO)-Phe-Phe-(NH-CH2-CH(NH2)-CO)-Asp-Cys- (SEQ ID NO: 2)” whereas claim 6 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 7 of ‘160 recites “The method according to claim 1, wherein said polymeric conjugate is selected from formula (a), (b), (c) or (d):(a) T-(NH-(CH2)7-CO)-Phe-Phe-(NH-CH2-CH(NH2)-CO)-Asp-Cys-PEG-LPEI (SEQ ID NO:17); (b) T-(NH-(CH2)7-CO)-Phe-Gly-Trp-Trp-Gly-Cys-PEG-LPEI(SEQ ID NO:18);(c) [T-(NH-(CH2)7-CO)-Phe-Phe-(NH-CH2-CH(NH2)-CO)-Asp-Cys-PEG]3-LPEI (SEQID NO:31); or (d) [T-(NH-(CH2)7-CO)-Phe-Gly-Trp-Trp-Gly-Cys-PEG]3-LPEI (SEQ ID NO:32); and wherein said T represents said targeting moiety” whereas claim 7 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 8 of ‘160 recites “The method according to claim 1, wherein said polymeric conjugate is selected from the group consisting of formula (i), (ii), (iii) and (iv):
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wherein said T represents said targeting moiety; and wherein n is 40-45” and whereas claim 8 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 10 of ‘160 recites “The method according to claim 1, wherein CRPC is non-metastatic CRPC or metastatic CRPC” and whereas claim 10 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 11 of ‘160 recites “The method according to claim 1, wherein said CRPC is androgen receptor (AR) independent CRPC” and whereas claim 11 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 12 of ‘160 recites “The method according to claim 11, wherein said androgen receptor (AR) independent CRPC is neuroendocrine prostate cancer” and whereas claim 12 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 13 of ‘160 recites “The method according to claim 1, wherein said polyplex is used in combination with immune cells” and whereas claim 13 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 14 of ‘160 recites “The method according to claim 13, wherein said immune cells are selected from the group consisting of tumor-infiltrating T-cells (T-TILs), tumor specific engineered T-cells and peripheral blood mononuclear cells (PBMCs)” and whereas claim 14 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 15 of ‘160 recites “A method of treating castration resistant prostate cancer (CRPC) comprising administering to a patient in need thereof, an effective amount of apharmaceutical composition, wherein said pharmaceutical composition comprises a pharmaceutically acceptable carrier and a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI), one or more polyethylene glycol (PEG) moieties, one or more linkers and one or more targeting moieties, wherein said LPEI is covalently bound to one or more PEG moieties and each of said one or more PEG moieties is conjugated via one of said one or more linkers to one of said one or more targeting moieties, wherein each of said one or more targeting moieties is capable of binding to a cancer antigen, and wherein said cancer antigen is prostate surface membrane antigen (PSMA)” and whereas claim 15 of the instant application recites the exact same scope and limitations and therefore renders the claims not patentably distinct.
Claim 16 of ‘160 recites “The method according to claim 1, wherein CRPC is metastatic CRPC” and whereas claim 16 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 17 of ‘160 recites “The method according to claim 1, wherein said CRPC is androgen receptor (AR) dependent” and whereas claim 17 of the instant application recites the exact same scope and limitations and therefore renders the claims not patentably distinct.
Claim 18 of ‘160 recites “The method according to claim 5, wherein said peptide moiety is -(NH-(CH2)7-CO)-Phe-Gly-Trp-Trp-Gly-Cys- (SEQ ID NO: 1)” and whereas claim 18 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 19 of ‘160 recites “The method according to claim I, wherein said polymeric conjugate is formula (b) T-(NH-(CH2)7-CO)-Phe-Gly-Trp-Trp-Gly-Cys-PEG-LPEI (SEQ ID NO: 18), wherein said T represents said targeting moiety” and whereas claim 19 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Claim 20 of ‘160 recites “The method according to claim 1, wherein said polymeric conjugate is of formula (ii):
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” and whereas claim 20 of the instant application recites the exact same scope and limitations and therefore claim the same invention.
Response to Arguments - Double Patenting
The previous rejection of claims 1, 3-8 and 10-20 under 35 U.S.C. 101 has been maintained in view of Applicant’s amendments to the claims filed on 07/24/2026.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
