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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a foreign application filed as EP17193577.8 on 09/27/2017.
All claims are given the priority date of 09/27/2017.
Application Status
Receipt is acknowledged of amendment, filed 10/18/2023. Claims 1-20 are currently pending.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statements filed on 05/12/2023 and 10/18/2023 have been received and all references have been considered.
Specification
The substitute specification filed on 10/18/2023 has been entered as it meets the requirements of 37 CFR 1.125.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Claims 7, 8 and 19 contain sequence with four or more specifically defined amino acids. Linear regions of 4 or more specifically defined amino acids are required to be in the sequence listing as well as identified by sequence identifiers within the claims (See 37 CFR 1.831(b) and 1.831(j)).
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located at pages 18-26 and 34-39 of the substitute specification and refers to SEQ ID NOS: 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30. However, the current sequence listing only has 16 sequences and do not contain the sequences identified as SEQ ID NOs: 17-30, respectively.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 3-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 3-20 are drawn to a genus of dsRNA. The dsRNA of the claims belongs to a general class of compounds. The rejected claims thus comprise a genus of dsRNA that encompass the ability to treat Castration Resistant Prostate Cancer (CRPC) within a patient.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes that the PPD/polyIC complex resulted in a strong retardation of tumor growth and the combined treatment with PPD/polyIC and PBMCs reduced size of the tumors or even led to tumor eradication (Page 50, Lines 24-27). No description is provided of any other dsRNA capable of treating CRPC within a patient.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of using polyIC as the dsRNA within the PEI/PEG/DUPA and polyIC polyplex complex for successful in vitro and in vivo treatment of CRPC cells. The results are not necessarily predictive of using any dsRNA complexed with the PEI/PEG/DUPA polyplex for in vitro and/or in vivo treatment of CRPC cells. Thus, it is impossible for one to extrapolate from the few examples described herein those dsRNA molecules that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe any other dsRNA, other than polyIC, capable of successful treatment of CRPC cells. As recently as 2020, Zhang et al (Am J Transl Res. 2020 Aug 15;12(8):4175-4188) teaches that little is known about which dsRNA have an inhibitory effect on prostate cancer (Page 4175, Abstract). Zhang teaches that there have been multiple studies reporting several miRNAs or dsRNA that could influence the proliferation and metastasis of PCa cells (Page 4175, Column 2). Zhang teaches that they transfected four dsRNAs (dsP21-242, dsP21-243, dsP21- 244, and dsP21-245) corresponding to the miR-1236-3p target sequence to PCa cells and found that only dsP21-245 could activate p21 expression; However, dsP21-245 had no effect on AKT pathway while activating p21 in PCa cells (Page 4176, Column 2). Thus, showing unpredictability in that not all dsRNAs are capable of binding and targeting the specific antigens and/or targets for treating prostate cancer.
Place et al (Mol Ther Nucleic Acids. 2012 Mar 27;1(3):e15; Pages 1-12) teaches that small activating dsRNAs showed inducible expression with variable strength depending on sequences and delivery for in vivo prostate tumor inhibition (Page 2, Column 1). Thus, the capability of the dsRNA is variable depending on the other additions to the complex and target for the treatment of prostate cancer.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1 and 3-20.
Claims 1 and 3-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating castration resistant prostate cancer (CRPR) 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 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) does not reasonably provide enablement for any dsRNA for the treatment castration resistant prostate cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: The claims are drawn to 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. The method comprises targeting a cancer antigen, specified as prostate surface membrane antigen (PSMA), for the binding and subsequent treatment of the castration resistant prostate cancer within a patient with a complexed dsRNA. The nature of the invention is complex in that the function of the dsRNA is specific to the disease being treated such that not any dsRNA is capable of targeting, binding and subsequently, treating castration resistant prostate cancer within a patient.
Breadth of the claims: The claims broadly encompass any dsRNA for use in a composition to treat castration resistant prostate cancer. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The instant specification defines the term "dsRNA" typically and preferably refers to double stranded ribonucleotide polymers of any length in which one or more ribonucleotides can be chemical analogues or modified derivatives of a corresponding naturally-occurring ribonucleotide (Page 9, Lines 30-32). The dsRNA is not limited to a specific dsRNA with a specific function or structure in order to successfully target and bind to the PSMA in order for treatment of the castration resistant prostate cancer.
Guidance of the specification and existence of working examples: The specification teaches the dsRNA is polyinosinic-polycytidylic acid double stranded RNA (polyIC) (Page 9, line 34 bridging to Page 10, Line 1).
Working example 1 teaches the preparation of the polyplex including the formation of the PEI-PEG-DUPA polyplex complexed with the polyIC dsRNA for the final complex formation (Pages 40-43).
Working example 2 teaches the assays completed for the structure and functions of the polyplex formula such assays include confocal microscopy, cell survival, western blot analysis, quantification of IP-10 and RANTES cytokines by ELISA and quantification of IFN-β, IFN-γ, IL-2 and TNF-α by qRT-PCR (Pages 43-45).
Working example 3 teaches in vitro and in vivo tests including in vitro analysis of bystander effects induced by PPD/polyIC treatment, Co-culture systems of LNCaP-Luc/GFP-PBMC, Co-culture system of LNCaP-PMBC-PC3-Luc/GFP, Co-culture system of PC3-PSMA-PBMC-MCF7-Luc/GFP and finally androgen-resistant prostate cancer xenograft model with reconstituted immune system (Pages 45-46).
Working example 4 teaches the results of the in vitro tests specifically showing that the PSMA ligand DUPA coupled to the polyplex comprising the PEI/PEG/PolyIC was capable to selectively target PSMA-overexpressing cancer cells (LNCaP cells) and delivers the polyplex composition of the invention to these cells (Page 46, Lines 19-22). The working example continues to teach the PEI/PEG/DUPA/polyIC complex was capable of selectively eradicates prostate cancer cells overexpressing PSMA (Page 47, Lines 9-13). Specifically, working example 4 teaches PPD/polyIC was tested for potency and selectivity; PSMA overexpressmg cells, LNCaP, VCaP and PC3-PSMA and PSMA non-overexpressing cells MCF7 and PC3 were treated for 4 days with PPD/polyIC, which efficiently killed 80-95% of PSMA overexpressing cells LNCaP, VCaP and PC3-PSMA cells, while leaving MCF7 and PC3 cells intact (Page 47, Lines 14-18). Working example 4 continues that the treatment with PPD/polyIC substantially increased cytokine secretion, induced chemotaxis, PBMC activation and induced bystander effects (Pages 47-49).
Working example 5 teaches results of the in vivo tests including systemic administration of a combination of PPD/polyIC with PBMCs induces regression of prostate tumor xenografts. The working example teaches the effect of PPD/polyIC on CrPC was investigated in an animal model for androgen resistant prostate cancer by using male NOD-SCID mice that were subcutaneously injected with PC3-PSMA cells (Page 50, Lines 6-8). The results show in the working example showed that the PPD/polyIC complex resulted in a strong retardation of tumor growth and the combined treatment with PPD/polyIC and PBMCs reduced size of the tumors or even led to tumor eradication (Page 50, Lines 24-27).
Working example 6 simply provides the protocols and guidelines for the cell cultures used within the experimentation (Page 51, Lines 4-17).
The working examples are only indicative of the polyIC as the dsRNA capable of targeting and binding the polyplex to the PSMA cells for the successful treatment of CRPC.
Predictability and state of the art:
For some relevant background, Wang et al (Cancer Letters 387 (Feb. 2017) Pgs. 77-83) teaches that the off-targeting gene silencing after siRNA administration underscores the importance of improved strategies for assessing RNAi but more stringent standards need to be introduced to not only siRNA design but also the design of negative controls (Page 81, Column 2). Wang teaches siRNA-based therapy still faces challenges in pharmaceutical manufacturing but still proves to be one of the most promising and rapidly advancing frontiers in current biomedicine and drug development (Page 82, Column 1).
Zhang et al (Am J Transl Res. 2020 Aug 15;12(8):4175-4188) teaches that little is known about which dsRNA have an inhibitory effect on prostate cancer (Page 4175, Abstract). Zhang teaches that there have been multiple studies reporting several miRNAs or dsRNA that could influence the proliferation and metastasis of PCa cells (Page 4175, Column 2). Zhang teaches that they transfected four dsRNAs (dsP21-242, dsP21-243, dsP21- 244, and dsP21-245) corresponding to the miR-1236-3p target sequence to PCa cells and found that only dsP21-245 could activate p21 expression; However, dsP21-245 had no effect on AKT pathway while activating p21 in PCa cells (Page 4176, Column 2). Thus, showing unpredictability in that not all dsRNAs are capable of binding and targeting the specific antigens and/or targets for treating prostate cancer.
Place et al (Mol Ther Nucleic Acids. 2012 Mar 27;1(3):e15; Pages 1-12) teaches that small activating dsRNAs showed inducible expression with variable strength depending on sequences and delivery for in vivo prostate tumor inhibition (Page 2, Column 1). Thus, the capability of the dsRNA is variable depending on the other additions to the complex and target for the treatment of prostate cancer.
Amount of experimentation necessary: In order to practice the claimed invention, an immense amount of experimentation would be required. As disclosed above, the specification itself provides description of the dsRNA as a polyIC dsRNA which has been shown capable of binding and targeting the PSMA for the subsequent treatment of CRPC. No description is provided of any other dsRNA that would be capable of the specific function of targeting and binding the PSMA for the subsequent selective treatment of CRPC tumor cells. Therefore, experiment could be conducted, but in view of the specification there does not appear to be any amount of experimentation that would be sufficient to reliably produce the exact product of the invention. Therefore, it would require immense amount of unpredictable experimentation to practice the claimed invention with such variants in the possible result.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 1 and 3-20 are not considered to be fully enabled by the instant disclosure.
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 1-20 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).
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 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 2, Levitzki teaches the dsRNA is polyinosinic-polycytidylic acid double
stranded RNA (poly I:C) [0041].
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 claims 8 and 9, 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):
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232
359
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233
486
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(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 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):
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Below shows the structure of the peptide moiety attached to the structure of formula (i) at the sulfur bond (referenced in Levitzki as R7):
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Claims 1-20 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).
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 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 2, Levitzki teaches the dsRNA is polyinosinic-polycytidylic acid double
stranded RNA (poly I:C) [0041].
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 claims 8 and 9, 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):
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(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 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):
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Below shows the structure of the peptide moiety attached to the structure of formula (i) at the sulfur bond (referenced in Levitzki as R7):
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(Page 12)
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 1-20 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 1-20, 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)” and 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 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)”. The two independent claims recite the same scope and limitations and therefore claim the same invention.
Claim 2 of ‘160 recites “The method according to claim 1, wherein said dsRNA is polyinosinic-polycytidylic acid double stranded RNA (polyIC)” whereas claim 2 of the instant application recites “The method according to claim 1, wherein said dsRNA is polyinosinic-polycytidylic acid double stranded RNA (polyIC)”. The two dependent 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 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)” and whereas claim 9 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.
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
/PATRICIA MALLARI/Director, Technology Center 1600