DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
In the official action filed 28 August 2025, claim 7 was inadvertently excluded from Group 1, claims 1-3 and 10-20. The claims included in Group 1 are 1-3, 7, and 10-20.
Claims 4-6 and 8-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 14 October 2025.
Claim Status
Claims 4-6 and 8-9 have been withdrawn, withdrawn claims 4-5 have been amended, claims 1-2, 7, 11, 13-14, and 18-20 have been amended, and claims 1-3, 7, and 10-20 have been considered on their merits.
Withdrawn Objections/Rejections
The claim objections directed to claims 13, 14, 18, 19, and 20 have been withdrawn due to Applicant’s amendment to the claims. However, not all objections were withdrawn because the corrections to claims 15 and 17 were not completed.
The claim rejections under 35 U.S.C. 112(b) have been withdrawn due to Applicant’s amendment to the claim.
The claim rejections under 35 U.S.C. 103 have been withdrawn due to Applicant’s amendments to the claims. However, upon further consideration, a new ground of rejection is made in view of Yan as evidenced by Lazear and Odendall.
Claim Objections
This is a new objection with regard to claim 7.
Claim 7 is objected to because of the following informalities: While the abbreviations of the symmetric phospholipids have been spelled out upon their first instance in the claims, the abbreviations should be enclosed within parentheses so as to avoid confusion with other options which may appear in the claims.
The objections with regard to claims 15 and 17 are repeated for the same reasons of record as set forth in the Official Action mailed 29 December 2025.
Claim 15 and 17 are objected to because of the following informalities: The phrase “claims 2” is grammatically incorrect. The word “claims” in the first line of the claim should read as “claim”.
Appropriate correction is required.
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 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Yan et al. (Biomedicine & Pharmacotherapy 88, published 2017, of record) as evidenced by Lazear et al. (Immunity 43, 21 July 2015, IDS ref.) and Odendall et al. (J Immunol. 01 November 2017; 199(9): 3270–3279).
This is a new rejection, necessitated by Applicant’s amendment to the claims. A response to Applicant’s traversal follows the new rejection below.
Regarding claim 1, Yan teaches use of IFN-λ3 as an adjuvant treatment with sorafenib in hepatocellular carcinoma (HCC) (Abstract). Yan teaches treatment with a combination of IFN-λ3 and sorafenib suppresses the viability of HepG2 and SMMC7721 liver cancer cell lines more than treatment with either alone (Abstract). Yan teaches Sorafenib is a small molecule multikinase inhibitor that is active in several cancer cell lines through its ability to inhibit cell proliferation, induce cell apoptosis, and suppress angiogenesis (p. 395, Introduction). Yan teaches sorafenib has gained acceptance as a first-line treatment for advanced and metastatic HCC (p. 396, 1st column). Yan teaches treatment with a combination of sorafenib and IFN-λ3 had a synergistic effect on tumor cell growth suppression (p. 398, Results). Yan teaches IFN-λ3 up-regulate IFN stimulated genes (ISGs) by binding to heterodimeric class II cytokine receptors through the Janus kinase/signal transducer and activator of transcription (Jak-STAT) intracellular signaling pathway (p. 399). Yan teaches non-tumoral hepatocytes lack sensitive response to sorafenib and IFN-λ3 co-treatment (p. 400). Yan teaches treatment with a combination of IFN-λ3 and sorafenib induced production of ROS in HepG2 and SMMC7721 liver cancer cell lines (Fig. 5).
Yan does not specifically point to IFN-λ3 tightening epithelial junctions, however, the effect of INF- λ3 on barrier cells of major organ tissues was known in the art, as evidenced by Lazear and Odendall.
Lazear teaches IFN-λ not only stimulates expression of antiviral interferon-stimulated genes (ISGs) preferentially in cells of epithelial origin, but additionally there have been additional mechanisms in other cell types and tissues (Abstract). Lazear teaches a specialized role for IFN-λ in providing antiviral activity at anatomic barriers, including epithelial surfaces and the blood-brain barrier (BBB) without activating a systemic pro-inflammatory immune response (p. 15, Introduction). While Lazear describes this effect as antiviral, the affect remains, IFN-λ provides protection at anatomic barriers, such as those found in major organ tissues. Lazear teaches epithelial cells are the predominant IFN-λ-responsive cell type in the gastrointestinal tract (p. 19, IFN-λ in the Gastrointestinal Tract). Lazear teaches IFN-λ stimulation at the BBB creates endothelial tightening (p. 21, IFN-λ at the BBB and Fig. 2D), and the BBB protects the brain, a major organ. Lazear teaches the tightening of the endothelial cells of the BBB restricts viral neuroinvasion and reduces viral titers of the CNS (p. 21, IFN-λ at the BBB). Additionally, Lazear teaches IFN-λ could have a prominent barrier effect in epithelial tissues where IFNLR expression is higher, such as in the skin where the IFN-λ receptor, IFNLR, is expressed predominantly on keratinocytes (p. 21, IFN-λ and Autoimmunity). Lazear teaches since IFN-λ can alter tumorigenesis directly and indirectly, it might have utility as an adjunctive anti-cancer therapy (p. 22, IFN-λ in Cancer).
Odendall teaches recombinant IFN-λs enhanced epithelial barriers in vitro (Abstract). Odendall teaches functionally, IFN-λs are particularly important at barrier surfaces, which are locations rich in epithelial cells that express high levels of IFN-λ receptors (p. 1, Introduction). Odendall teaches recombinant IFN-λs increased the barrier functions of polarized human intestinal epithelial cell lines (p. 3, Introduction). Odendall teaches IFN-λs appear to play an important role of reinforcing epithelial and endothelial barriers (p. 11, Discussion).
Yan as evidenced by Lazear and Odendall teach administering both the composition to induce tightening of epithelial and/or endothelial junctions in non-tumor tissues (IFN-λ) and administering an anti-cancer agent (sorafenib); however, is silent to the order in which the composition and anti-cancer agent are administered.
However, the order of administration of the composition to induce tightening of epithelial junctions in non-tumor tissues and administering an anti-cancer agent would have been readily optimizable by one having ordinary skill in the art by routine experimentation in order to achieve optimal results. MPEP2144.04(IV)(C). Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).
Since the effects of both IFN-λ and sorafenib were known in the art, there would have been a reasonable expectation of success in administering the IFN-λ prior to the sorafenib because Yan proposed adding IFN-λ3 to traditional sorafenib therapy may provide increased benefit to patients with HCC (p. 396, 1st column) and Lazear teaches since IFN-λ can alter tumorigenesis directly and indirectly, therefore may have utility as an adjunctive anti-cancer therapy (p. 22, IFN-λ in Cancer). There being a finite order of administration; IFN-λ first, sorafenib first, or IFN-λ and sorafenib simultaneously; one would be able to discover the optimal order to achieve ideal results via routine experimentation.
Regarding the limitation “wherein the predosing reduces uptake or accumulation of the anti-cancer agent in nontumor major organ tissue by at least 8% compared to uptake or accumulation of the anti-cancer agent in the absence of pre-dosing.”, in the last three lines of the claim, are considered intended results. MPEP 2111.04(I) states, “The court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. Therefore, because the method steps are recited by the prior art, the intended results would necessarily occur.
Regarding claim 18, the wherein clause of the claim, “wherein said predosing reduces uptake or accumulation of an anti-cancer agent in nontumor major organ tissues for a duration of from 3 hours to about 28 days after predosing.”, are considered intended results. MPEP 2111.04(I) states, “The court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. Therefore, because the method steps are recited by the prior art, the intended results would necessarily occur.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Traversal
Applicant’s arguments, see Remarks, filed 26 March 2026, with respect to the rejections of claims 1-3, 7, and 10-20 under 35 USC 103 have been fully considered and are persuasive. Specifically, the rejections of record did not address the newly added limitation directed to nontumor major organ tissue.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Yan teaches both administration of both IFN-λ (predosing element) and sorafenib (the anti-cancer agent). The evidentiary references were included in the rejection because they teach the inherent properties of the IFN-λ, which includes tightening of epithelial and endothelial junctions of nontumor major organ tissues, to include brain, intestine, and skin.
In response to applicant's argument on page 10 of the remarks, that the invention in the claims is directed to reduction of accumulation of a tumor agent in non-tumor organs and the method in the claims are directed to the tightening of the epithelium or endothelium junctions such that there is reduced uptake are considered intended results, a recitation of the intended results of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Additionally, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Claims 2-3, 10-14, 16-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Yan et al. (Biomedicine & Pharmacotherapy 88, published 2017, of record) as evidenced by Lazear et al. (Immunity 43, 21 July 2015, IDS ref.) and Odendall et al. (J Immunol. 01 November 2017; 199(9): 3270–3279) as applied to claims 1 and 18 above, and further in view of Liang et al. (Oncotarget, Vol. 7, No. 32, published 11 July 2016, of record).
This is a new rejection, necessitated by Applicant’s amendment to the claims. A response to Applicant’s traversal follows the new rejection below.
Regarding claims 2 and 10, the composition of Yan as evidenced by Lazear and Odendall reads as a composition comprising IFN-λ.
Yan as evidenced by Lazear and Odendall do not teach wherein the composition comprises a nucleic acid (claim 2), wherein the nucleic acid is double stranded DNA (claim 10).
Liang teaches lipoplex delivery of a recombinant cytokine for immunotherapy for colon cancer (Abstract). Liang teaches DNA-liposome complexes (lipoplexes) are formed by electrostatic interaction between DNA and two or more cationic liposomes resulting in a DNA-liposome complex (p. 52208, Results). Liang teaches the plasmid DNA (double stranded DNA) (claim 10) encoding IL-15 in the folate-modified PEGylation liposome (F-PLP/IL15) provided increased stability compared to naked pIL15 when exposed to DNase I (p. 52208, Results).
It would have been obvious to one of ordinary skill in the art to deliver the IFN-λ of Yan with the lipoplex of Liang with a reasonable expectation of success because Liang teaches lipoplexes comprising cytokines can be used in a method of treating cancer and the use of the lipoplexes taught by Liang provide increased stability of the cytokine compared to naked pIL15. One would be motivated to deliver the IFN-λ of Yan with the lipoplex of Liang because Liang teaches lipoplexes can be used for delivering cytokines as part of cancer immunotherapy and Yan teaches IFN-λ can be utilized as part of cancer treatment. Additionally, lipoplexes offer simple production methods as well as the ability to be readily modified, such as PEGylation or targeting ligands as taught by Liang, which could result in increased circulation time or specific cell targeting.
Regarding claim 3, Liang teaches the DNA-liposome complexes have a size of 250-300 nm, therefore, the liposome reads as comprising a lipid nanoparticle (p. 52208, Results). According to the instant specification at para. [0108], which identifies a lipid nanoparticle having a diameter from about 10 nm up to greater than 1000 nm.
Regarding claim 11, Yan teaches in a tumorigenicity assay in a mouse model, IFN-λ3 was administered via tail vein injection (p. 397, section 2.13). Tail vein injection reads as administered parenterally.
Regarding claim 12, Yan teaches the anti-cancer agent is sorafenib, a small molecule multikinase inhibitor that is active in several cancer cell lines through its ability to inhibit cell proliferation, induce cell apoptosis, and suppress angiogenesis (p. 395, Introduction). Sorafenib reads as an anti-cancer agent which lacks nucleic acids. The limitations of claim 12 are listed in the alternative, therefore, sorafenib reads on the limitations of the claim.
Regarding claim 13, Yan teaches a tumorigenicity assay in a mouse model utilizing tumors formed by SMMC7721 cells (p. 397, section 2.13). Yan teaches treatment of human hepatocellular carcinoma (HHC) cells; HepG2, SMMC7721, SK-Hep-1, and BEL-7402 (p. 396, section 2.3). HHC cells are solid tumor forming cells.
Regarding claims 14 and 16, Yan teaches teach IFN-λ3 is injected into the tail vein every day (reads as repeated about 24 hours) (claim 16) for 28 days and the anti-cancer agent is administered every day for 28 days via intragastric administration (p. 397, section 2.13). Claim 14 is interpreted as requiring the predosing is repeated prior to each dose of the anti-cancer agent.
Regarding the order in which predosing and anti-cancer agent are administered, as discussed in the rejection of claim 1, Yan does not indicate the order in which the composition and anti-cancer agent are administered, however, the order in which the predosing composition and the anti-cancer agent would have been readily optimizable by one having ordinary skill in the art by routine experimentation in order to achieve optimal results. The order of administration of the composition to induce tightening of epithelial junctions in non-tumor major organ tissues and administering an anti-cancer agent would have been readily optimizable by one having ordinary skill in the art by routine experimentation in order to achieve optimal results. MPEP2144.04(IV)(C). Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).
Regarding claim 17 directed to the predosing is administered from 5-120 minutes prior to administration of the anti-cancer agent, Yan as evidenced by Lazear and Odendall in view of Liang are silent to the timing of the predosing and anti-cancer agent administration. However, the timing of doses in a method for treating cancer would have been readily optimizable by one having ordinary skill in the art by routine experimentation in order to achieve optimal cancer treatment. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05. MPEP2144.04(IV)(C). Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).
Regarding claim 19, Yan teaches administration of IFN-λ3, which was shown to provide the tightening of epithelial junctions as evidenced by Lazear and Odendall, see the rejection of claim 1. Yan as evidenced by Lazear and Odendall do not teach a method comprising selectively reducing uptake or off-target accumulation of an agent in nontumor tissue of a subject and do not teach wherein the composition comprises a nucleic acid.
Liang teaches the alpha isoform of the folate receptor (FRα) is associated with tumor cell proliferation, migration, and invasion, with FRα overexpressed in approximately 30-40% of human colorectal carcinoma tissues (p. 52208, Introduction). Liang teaches FRα-targeted non-viral vectors potentially having a place in colon cancer immunogene therapy (p. 52208, Introduction). Liang teaches the lipoplex comprising the plasmid DNA encoding IL-15 in the folate-modified PEGylation liposome (F-PLP/IL15) (a target specific lipoplex) provided increased stability compared to naked pIL15 when exposed to DNase I (p. 52208, Results).
It would have been obvious to one of ordinary skill in the art to deliver the IFN-λ of Yan with the targeted lipoplex of Liang with a reasonable expectation of success because Liang teach targeted lipoplexes comprising cytokines can be used in a method of treating cancer and the use of the lipoplexes taught by Liang provide increased stability of the cytokine compared to naked pIL15 and Yan teaches IFN-λ3 was shown to provide the tightening of epithelial junctions. One would be motivated to deliver the IFN-λ of Yan with the targeted lipoplex of Liang because Liang teaches lipoplexes can be used for delivering cytokines to a selected group of cells via the ability to design a lipoplex with a specific targeting moiety and Yan teaches IFN-λ can be utilized as part of cancer treatment, which would provide the tightening of epithelial junctions. Additionally, lipoplexes offer simple production methods as well as the ability to be readily modified, such as PEGylation or targeting ligands as taught by Liang, which could result in increased circulation time or specific cell targeting.
Regarding claim 20, Liang et al. teach the DNA-liposome complexes have a size of 250-300 nm, therefore, the liposome reads as comprising a lipid nanoparticle (p. 52208, Results). According to the instant specification at para. [0108], which identifies a lipid nanoparticle having a diameter from about 10 nm up to greater than 1000 nm.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Traversal
Applicant argues Liang do not cure the deficiencies of Yan. This argument is merely the argument of counsel and is unsupported by evidence or declarations of those skilled in the art. Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See M.P.E.P. § 2129 and § 2144.03 for a discussion of admissions as prior art. Counsel's arguments cannot take the place of objective evidence. In re Schulze, 145 USPQ 716 (CCPA 1965); In re Cole, 140 USPQ 230 (CCPA 1964); and especially In re Langer, 183 USPQ 288 (CCPA 1974). See M.P.E.P. § 716.01(c) for examples of attorney statements that are not evidence and that must be supported by an appropriate affidavit or declaration.
Claims 7 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Yan et al. (Biomedicine & Pharmacotherapy 88, published 2017, of record) as evidenced by Lazear et al. (Immunity 43, 21 July 2015, IDS ref.) and Odendall et al. (J Immunol. 01 November 2017; 199(9): 3270–3279) in view of Liang et al. (Oncotarget, Vol. 7, No. 32, published 11 July 2016, of record), as applied to claims 2-3, 10-14, 16-17, and 19-20 above, and further in view of Betker et al. (Journal of Pharmaceutical Sciences 106 (2017), published 22 November 2016, IDS ref., of record).
This is a new rejection, necessitated by Applicant’s amendment to the claims. A response to Applicant’s traversal follows the new rejection below.
Regarding claim 7, Liang teaches DOTAP, Cholesterol, and F-PEG-suc-Chol were used to prepare the folate-modified PEGylation liposome (F-PLP) (p. 52214, 1st column).
Yan as evidenced by Lazear and Odendall in view of Liang et al. do not teach wherein the lipid NP is formulated with asymmetric phospholipid: structural lipid: symmetric phospholipid.
However, Betker teaches sphingosine (asymmetric phospholipid), 1,2-diarachidoyl-sn-glycero-3-phosphocholine (DAPC) (symmetric phospholipid), and cholesterol (structural lipid) where used to prepare liposomes at a 3:2:5 mole ratio (p. 873, Materials and Methods). Betker teaches these liposomes were mixed with a modified pSelect-LucSh plasmid encoding luciferase, thereby, forming the lipoplex (p. 873, Materials and Methods). Betker teaches their lipoplexes composed of naturally occurring lipids (i.e., phosphatidylcholine, cholesterol, sphingosine) greatly reduce their toxicity and potential immunogenicity, as compared to other gene delivery vehicles (p. 877, Discussion). Betker teaches lipoplex formulations comprising DOTAP, PEG, or lipofectamine elicited elevation of a large number of cytokines and chemokines (Fig. 2 and Table 1), which can lead to IgM production and subsequent accelerated blood clearance (ABC) (p. 877, Discussion).
Therefore, it would have been obvious to one of ordinary skill in the art to utilize the lipoplex composition of Betker in the method of Yan in view of Liang with a reasonable expectation of success because Betker teaches their lipoplexes composed of naturally occurring lipids (i.e., phosphatidylcholine, cholesterol, sphingosine) greatly reduce their toxicity and potential immunogenicity, as compared to other gene delivery vehicles. One would be motivated to utilize the lipoplex of Betker in the method of Yan in view of Liang because Betker teaches the benefits of the lipoplex formulation comprising phosphatidylcholine, cholesterol, sphingosine in comparison to the formulations comprising DOTAP and PEG as taught by Liang.
Regarding claim 15, Yan as evidenced by Lazear and Odendall in view of Liang do not teach predosing is repeated four times prior to receiving a dose of the anti-cancer agent.
However, Betker teaches repeated administration of the lipoplex composition resulted in both plasmid levels (26-fold) and luciferase (plasmid) expression (10-fold) in the tumor are enhanced by more than 4-fold after the fourth dose as compared to that after a single administration (p. 876, Tumor Accumulation and Expression). Betker teaches repetitive administration enhances delivery is consistent with previous studies with both plasmid DNA and siRNA, suggesting delivery is increased beyond that seen after the initial administration, which was observed by successive injections 3 days apart (p. 878, 1st column). Betker teaches plasmid delivered to nontumor cells exhibit delayed expression due to reduced rates of cell division, and this contributes to the much larger enhancement of expression observed at later times, i.e., after 4 injections (p. 878, 2nd column).
Therefore, it would have been obvious to one of ordinary skill in the art to repeat predosing four times prior to receiving a dose of the anti-cancer agent in the method of Yan as evidenced by Lazear and Odendall in view of Liang with a reasonable expectation of success because Betker teaches an enhancement of expression in nontumor cells following multiple injections. This finding suggests prolonged epithelial junction tightening in the nontumor cells surrounding the tumor cells. One would have been motivated to repeat predosing up to four times prior to receiving a dose of the anti-cancer agent in the method of Yan as evidenced by Lazear and Odendall in view of Liang because enhanced expression, as indicated by Betker, of the lipoplex predosing composition could lead to increased uptake or accumulation of the anti-cancer agent in the tumor tissue compared to nontumor tissue.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Traversal
Applicant argues Betker do not cure the deficiencies of Yan. This argument is merely the argument of counsel and is unsupported by evidence or declarations of those skilled in the art. Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See M.P.E.P. § 2129 and § 2144.03 for a discussion of admissions as prior art. Counsel's arguments cannot take the place of objective evidence. In re Schulze, 145 USPQ 716 (CCPA 1965); In re Cole, 140 USPQ 230 (CCPA 1964); and especially In re Langer, 183 USPQ 288 (CCPA 1974). See M.P.E.P. § 716.01(c) for examples of attorney statements that are not evidence and that must be supported by an appropriate affidavit or declaration.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICHOLAS A. HUMPHRIES whose telephone number is (703)756-5556. The examiner can normally be reached Monday - Friday, 7:30am - 4:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
Prosecution Insights