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 .
The amendments and remarks filed 2/19/26 are acknowledged. Claims 24, 26, 31, 44, and 49 have been amended. Claims 56-63 have been added. Claims 1-23, 25, 27, 32-43, 50-55 have been canceled. Claims 24, 26, 28-31, 44-49, and 56-63 are pending and under examination.
Withdrawn Rejections
The rejection of claims 49-55 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, is withdrawn in light of Applicant’s amendment thereto. See paragraph 5, page 2 of the previous Office action.
The rejection of claim 26 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in light of Applicant’s amendment thereto. See paragraph 7, page 11 of the previous Office action.
The rejection of claims 47 and 48 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in light of Applicant’s persuasive arguments. See paragraph 7, page 11 of the previous Office action.
The rejection of claims 24, 27, 30, and 45-46 under 35 U.S.C. 102(a)(1) as being anticipated Corti et al. (J. Nanobiotechnol, 2021, 19:128), is withdrawn in light of Applicant’s amendment thereto. See paragraph 10, page 12 of the previous Office action.
The provisional rejection of claims 24-31, 44, 49-50, and 53 on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 18/358,510 (reference application), is withdrawn in light of Applicant’s cancelation of the copending claims. See paragraph 12, page 14 of the previous Office action.
New Rejections Necessitated by Applicant’s Amendment
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.
Claim(s) 24, 26, 28, 30, 31, 44-47, 49, and 56-63 is/are rejected under 35 U.S.C. 103 as being unpatentable over Paciotti et al. (Cancer Res (2005) 65 (9_Supplement): 337–338; herein referred to as Paciotti 2005) in view of Tamarkin et al. (WO 2009/039502 A1, published March 26, 2009).
The instant claims are drawn to a composition comprising a gold nanoparticle bound to a first cytokine and a second cytokine, wherein the first cytokine comprises Tumor Necrosis Factor alpha (TNFa), and the second cytokine comprises interferon λ (IFNλ).
Paciotti 2005 teach AuriTax, a multivalent drug, assembled on 25 nm colloidal gold (cAu) particles and designed to deliver TNF and paclitaxel to solid tumors (See page 1). Paciotti 2005 teach that the drug is manufactured by covalently binding TNF, a thio-pyridyl derivative of paclitaxel, and thiolated polyethylene glycol (PEG-THIOL) onto the surface of cAu particles (See page 1). Paciotti 2005 teach that each component of the drug serves a specific function to achieve tumor targeted drug delivery. Paciotti 2005 teach the cAu particles limit the biodistribution of the drug by preferential extravasation of the leaky tumor neovasculature (See page 1). Paciotti 2005 teach the PEG-THIOL moiety hydrates the cAu particles and shields them from detection and clearance by the RES (See page 1). Paciotti 2005 teach TNF not only acts as one of the anti-tumor therapeutics delivered by AuriTax, but also as a targeting ligand, that binds to cell-surface receptors in and around the solid tumor (See page 1). Paciotti 2005 teach the paclitaxel derivative acts as a second therapeutic (See page 1). Paciotti 2005 teach that the gold nanoparticle comprising TNF and paclitaxel localized within solid tumors and sequences ten times the amount of TNF and paclitaxel compared to native drug treatment in the B16F10 melanoma mouse model (See page 2). Paciotti 2005 teach that the formulation also improved anti-tumor efficacy in vivo since it prevented the progression of B16F10 tumors in vivo, compared to animals receiving the native treatment, in which tumors continued to grow (See page 2).
Paciotti 2005 does not teach wherein the gold nanoparticle comprises IFNλ.
Tamarkin et al. teach a composition comprising a gold nanoparticle, a targeting agent, and one stealth agent, and at least one therapeutic agent (See claims 1-2 and pages 10 and 12). Tamarkin et al. teach that the one or more agents are associated with or bound directly or indirectly with the colloidal metal and binding includes covalent or ionic bonds, and other weaker or stronger associations that allow for long term or short term association of the derivatized-PEG, agents, and other components with each other and with the metal sol particles (See page 11). Tamarkin et al. teach that the targeting agent is IFN gamma and TNF alpha (See page 14). Tamarkin et al. teach that the PEG comprises a thiol and the molecular weight of the PEG is 5-40 kDa (See page 17).
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 gold nanoparticle of Paciotti 2005 by covalently adhering IFN-γ to the gold nanoparticle to have prepared a gold nanoparticle functionalized with TNFα, IFN-γ, PEG-THIOL, and paclitaxel for targeted delivery of the agents to tumors for treating cancer. Paciotti 2005 has established that gold nanoparticle functionalized with TNFα, PEG-THIOL, and paclitaxel enhance the anti-tumor response in melanoma. Similarly, Tamrkin et al. teach that gold nanoparticles can be functionalized with IFN-γ for targeted delivery of IFN-γ to tumors and enhanced immune response to the tumor. One of ordinary skill in the art would be motivated to prepare a gold nanoparticle comprising TNFα, IFN-γ, PEG-THIOL, and paclitaxel for the benefit of improving the delivery of the agents to tumor and improving the anti-tumor response of each of the agents. One of ordinary skill in the art would have a reasonable expectation of success because both Paciotti 2005 and Tamarkin et al. teach that gold nanoparticles can be functionalized with multiple agents.
Regarding the ratio of TNFα to IFN-γ, Tamarkin et al. teach the skilled artisan is able to control the amount of biologically-active factor delivered by varying the amount of biologically- active factor initially bound to the colloidal metal. Thus, the art recognizes that the amount of TNFα and IFN-γ bound to the gold nanoparticle is a result effective variable that can be optimized by one of ordinary skill in the art. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Although Kakkar et al. teach a dose range that does not overlap, but is close, with the claimed dose range, Applicant has not demonstrated criticality of the claimed dose, and determining the optimal concentration COR-001 would be well within the knowledge of the skilled artisan.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claim(s) 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Paciotti et al. (Cancer Res (2005) 65 (9_Supplement): 337–338; herein referred to as Paciotti 2005) in view of Tamarkin et al. (WO 2009/039502 A1, published March 26, 2009) as applied to claims 24, 26, 28, 30, 31, 44-47, 49, and 56-63 above, and further in view of Lu et al. (Chem Sci. 2017 Jun 22;8(9):6182–6187).
Claim 29 adds the limitation wherein the gold nanoparticle is covalently bound to the first cytokine via a first thiol group and the gold nanoparticle is covalently bound to the second cytokine via a second thiol group.
Paciotti 2005 teach AuriTax, a multivalent drug, assembled on 25 nm colloidal gold (cAu) particles and designed to deliver TNF and paclitaxel to solid tumors (See page 1). Paciotti 2005 teach that the drug is manufactured by covalently binding TNF, a thio-pyridyl derivative of paclitaxel, and thiolated polyethylene glycol (PEG-THIOL) onto the surface of cAu particles (See page 1). Paciotti 2005 teach that each component of the drug serves a specific function to achieve tumor targeted drug delivery. Paciotti 2005 teach the cAu particles limit the biodistribution of the drug by preferential extravasation of the leaky tumor neovasculature (See page 1). Paciotti 2005 teach the PEG-THIOL moiety hydrates the cAu particles and shields them from detection and clearance by the RES (See page 1). Paciotti 2005 teach TNF not only acts as one of the anti-tumor therapeutics delivered by AuriTax, but also as a targeting ligand, that binds to cell-surface receptors in and around the solid tumor (See page 1). Paciotti 2005 teach the paclitaxel derivative acts as a second therapeutic (See page 1). Paciotti 2005 teach that the gold nanoparticle comprising TNF and paclitaxel localized within solid tumors and sequences ten times the amount of TNF and paclitaxel compared to native drug treatment in the B16F10 melanoma mouse model (See page 2). Paciotti 2005 teach that the formulation also improved anti-tumor efficacy in vivo since it prevented the progression of B16F10 tumors in vivo, compared to animals receiving the native treatment, in which tumors continued to grow (See page 2).
Paciotti 2005 does not teach wherein the gold nanoparticle comprises IFNλ.
Tamarkin et al. teach a composition comprising a gold nanoparticle, a targeting agent, and one stealth agent, and at least one therapeutic agent (See claims 1-2 and pages 10 and 12). Tamarkin et al. teach that the one or more agents are associated with or bound directly or indirectly with the colloidal metal and binding includes covalent or ionic bonds, and other weaker or stronger associations that allow for long term or short term association of the derivatized-PEG, agents, and other components with each other and with the metal sol particles (See page 11). Tamarkin et al. teach that the targeting agent is IFN gamma and TNF alpha (See page 14). Tamarkin et al. teach that the PEG comprises a thiol and the molecular weight of the PEG is 5-40 kDa (See page 17).
Paciotti and Tamarkin do not teach wherein the gold nanoparticle is covalently bound to the first cytokine via a first thiol group and the gold nanoparticle is covalently bound to the second cytokine via a second thiol group.
Liu et al. teach a thiol-ene crosslinker for bioconjugation of colloidal materials (See page 6183 and scheme 1). Liu et al. teach that cysteine is an ideal residue for the chemical modification of proteins based on the unique reactivity of the thiol group and low abundance of cysteine residues in natural proteins (See page 6185). Liu et al. teach that therefore, cysteine selective conjugation for bionanoconjugates is desired (See page 6185). Liu et al. teach that the thiol-ene linkage is stable (See page 6186). Liu et al. teach that the superior selectivity and stability of the thiol–ene adduct will enable engineering of multifunctional nanomaterial bioconjugates, making this a powerful tool with broad applications in bio sensing, bioanalysis, bioimaging, drug delivery, and theranostics (See page 6186).
It would be prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Paciotti and Tamarkin by using the thiol-ene reaction to conjugate the TNFα and IFNγ to the gold nanoparticle because Liu et al. teach that the method allows for the stable bioconjugation of any thiol containing biomolecule to colloidal nanoparticles. One of ordinary skill in the art would be motivated to covalently bind the TNFα and IFNγ to the gold nanoparticle via a thiol linker because doing so would provide a stable and robust mechanism for attaching the TNFα and IFNγ to the gold nanoparticle. One of ordinary skill in the art would have a reasonable expectation of success because both TNFα and IFNγ contain cysteine residues and the art has demonstrated that gold nanoparticle can be functionalized with proteins in a cysteine-selective manner via a thiol-linkage.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one product, and a person of ordinary skill would recognize that it would be used in similar products in the same way, using the technique is obvious unless its application is beyond that person’s skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that “The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results”.
Thus, the combination of prior art references to arrive at the claimed invention provided a prima facie case of obviousness, absent evidence to the contrary.
Claim(s) 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Paciotti et al. (Cancer Res (2005) 65 (9_Supplement): 337–338; herein referred to as Paciotti 2005) in view of Tamarkin et al. (WO 2009/039502 A1, published March 26, 2009) as applied to claims 24, 26, 28, 30, 31, 44-47, 49, and 56-63 above, and further in view of Praveen et al. (WO 2012/039685 A1, published March 29, 2012).
Claim 48 adds the limitation wherein the first cytokine and/or second cytokine are bound to the gold nanoparticle using hydrophobic interactions.
Paciotti 2005 teach AuriTax, a multivalent drug, assembled on 25 nm colloidal gold (cAu) particles and designed to deliver TNF and paclitaxel to solid tumors (See page 1). Paciotti 2005 teach that the drug is manufactured by covalently binding TNF, a thio-pyridyl derivative of paclitaxel, and thiolated polyethylene glycol (PEG-THIOL) onto the surface of cAu particles (See page 1). Paciotti 2005 teach that each component of the drug serves a specific function to achieve tumor targeted drug delivery. Paciotti 2005 teach the cAu particles limit the biodistribution of the drug by preferential extravasation of the leaky tumor neovasculature (See page 1). Paciotti 2005 teach the PEG-THIOL moiety hydrates the cAu particles and shields them from detection and clearance by the RES (See page 1). Paciotti 2005 teach TNF not only acts as one of the anti-tumor therapeutics delivered by AuriTax, but also as a targeting ligand, that binds to cell-surface receptors in and around the solid tumor (See page 1). Paciotti 2005 teach the paclitaxel derivative acts as a second therapeutic (See page 1). Paciotti 2005 teach that the gold nanoparticle comprising TNF and paclitaxel localized within solid tumors and sequences ten times the amount of TNF and paclitaxel compared to native drug treatment in the B16F10 melanoma mouse model (See page 2). Paciotti 2005 teach that the formulation also improved anti-tumor efficacy in vivo since it prevented the progression of B16F10 tumors in vivo, compared to animals receiving the native treatment, in which tumors continued to grow (See page 2).
Paciotti 2005 does not teach wherein the gold nanoparticle comprises IFNλ.
Tamarkin et al. teach a composition comprising a gold nanoparticle, a targeting agent, and one stealth agent, and at least one therapeutic agent (See claims 1-2 and pages 10 and 12). Tamarkin et al. teach that the one or more agents are associated with or bound directly or indirectly with the colloidal metal and binding includes covalent or ionic bonds, and other weaker or stronger associations that allow for long term or short term association of the derivatized-PEG, agents, and other components with each other and with the metal sol particles (See page 11). Tamarkin et al. teach that the targeting agent is IFN gamma and TNF alpha (See page 14). Tamarkin et al. teach that the PEG comprises a thiol and the molecular weight of the PEG is 5-40 kDa (See page 17).
Paciotti and Tamarkin do not teach wherein the gold nanoparticle is covalently bound to the first cytokine via a first thiol group and the gold nanoparticle is covalently bound to the second cytokine via a second thiol group.
Praveen et al. teach a gold nanoparticle comprising a molecule non-covalently adsorbed to the surface of the nanoparticle (See claim 1). Praveen et al. teach that the non-covalent interaction is a hydrophobic interaction (See claim 2). Praveen et al. teach that hydrophobic interactions do not alter the structure of the agent attached to the gold nanoparticle, as there is no structural change involved in the adsorption process (See paragraph 0047).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined gold nanoparticle of Paciotti and Tamarkin by binding the first cytokine and/or second cytokine to the gold nanoparticle using hydrophobic interactions because Praveen et al. teach that hydrophobic interactions can also be used to attach agents to gold nanoparticle. Given that Tamarkin et al. teach that agents may be attached to the gold nanoparticle via weaker associations, it would be obvious to one of ordinary skill in the art that alternative interactions, such a hydrophobic interactions, can be used to bind the TNFα and IFNγ to the gold nanoparticle. One of ordinary skill in the art would be motivated to use hydrophobic interactions to bind the TNFα and IFNγ to the gold nanoparticle because doing so would provide an alternative means for functionalizing the gold nanoparticle, without any structural changes involved in the adsorption process, and with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one product, and a person of ordinary skill would recognize that it would be used in similar products in the same way, using the technique is obvious unless its application is beyond that person’s skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that “The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results”.
Thus, the combination of prior art references to arrive at the claimed invention provided a prima facie case of obviousness, absent evidence to the contrary.
Claim Status
No claims are allowed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SANDRA CARTER/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674