FINAL 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 .
Status of the Claims
This action is in response to papers filed 10/23/2025 in which claims 2-4 and 7-14 were withdrawn; claims 20-24 were withdrawn; claims 1 and 20 were amended; and claims 25-29 were newly added . All the amendments have been thoroughly reviewed and entered.
Claims 1, 5-6, 15-19, and 25-29 are under examination.
Withdrawn Objections/Rejections
The Examiner has re-weighted all the evidence of record. Any rejection and/or objection not specifically addressed below is hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Interpretation
Claims 27-29 are structured as a product-by-process. Thus, claims 27-29 will be interpreted and examined for art rejections purposes (103 rejections) as product-by-process type claims. MPEP 2113 (I) states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Thus, while the structure implied by the process steps should be consider when assessing patentability of product-by-process claims over the prior art; however, burden of proof is placed upon Applicant to show that the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). Also see MPEP § 2113.
New Rejections
Necessitated by Applicant’s Claim Amendments
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 15-18 and 25-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kreuter et al (22 October 2009; US 2009/0263491 A1) in view of Chitkara et al (Pharm Res., 2013, 30: 2396-2409), Wang et al (AAPS PharmSciTech, December 2009, 10(4): 1263-1267), and Wu (US 2016/0310426 A1; PCT filed date: 4 December 2013).
The product-by-process Claim Interpretation applies here.
Regarding claims 1 and 27, Kreuter teaches a polymeric nanoparticle comprising an aqueous core enclosed in polymeric shell, wherein the aqueous core contains a hydrophilic therapeutic agent and the polymeric shell is formed from polymer such as PLGA-COOH (Abstract; [0012], [0015], [0017]-[0019], [0029], [0035]-[0047], [0107]-[0134] and [0145]). Kreuter teaches the polymer is solubilized in an organic solvent such as dichloromethane or chloroform ([0082] and [0095]-[0096]). Kreuter teaches the polymeric nanoparticle has a particle size of between 130 and 160 nm ([0041], [0107]-[0134]). Kreuter teaches the polymeric nanoparticles is produced by double emulsion technique ([0035], [0110], [0112], [0114]-[0118], [0120], [0122] and [0126]) and has high drug loading ([0110], [0112], [0114]-[0118], [0120], [0122] and [0126]).
However, Kreuter does not teach the polymeric shell has a thickness less than 25 nm; the polymeric nanoparticle is free of a surfactant; and the polymeric nanoparticle is formed in the presence of a polar aqueous solution containing phosphate, bicarbonate, Tris or a combination thereof, of claims 1 and 27, respectively.
Regarding the polymeric shell has a thickness less than 25 nm of claim 1, Chitkara teaches PLGA nanoparticle containing an aqueous core containing a hydrophilic drug (Abstract; page 2397, right column; page 2398, left column; page 2399 and Table 1; page 2400, right column; page 2401 and Fig. I; pages 2402-2403; page 2406, right column). Chitkara teaches the nanoparticles are produced by double emulsion technique and has high drug loading (page 1398, left column and pages 2401-2403). Chitkara teaches the thickness of the outer shell of the PLGA nanoparticle is 5-10 nm (page 2401, left column).
It would have been obvious to one of ordinary skill in the art to routinely optimize the thickness of the shell of the polymeric nanoparticle of Kreuter to a thickness of 5-10 nm, per guidance from Chitkara, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Chitkara provided the guidance to do so by teaching that the shell of the PLGA nanoparticles encapsulating a hydrophilic drug/compound which are produced by a double emulsion of water-in-oil-in-water, can be controlled or optimize to have a thickness of 5-10 nm, and such resultant polymeric nanoparticles have increased encapsulation efficiency of hydrophilic substances (Chitkara: left column; page 2399 and Table 1; page 2400, right column; page 2401 and Fig. I; pages 2402-2403; page 2406, right column), which is also the objective of Kreuter, to provide a PLGA nanoparticle with an increase encapsulation efficiency of the hydrophilic active ingredient (Kreuter: [0110], [0112], [0114]-[0118], [0120], [0122] and [0126]).
Regarding polymeric nanoparticle is free of a surfactant of claims 1 and 27, Wang teaches a surfactant free-formulation of PLGA nanoparticles encapsulating a therapeutic protein or polypeptide (Title; page 1263, Introduction; pages 1264-1266). Wang teaches that polyvinyl alcohol (PVA) is widely used polymeric surfactant in the exterior aqueous phase as an emulsifier, but the safety of PVA still appears to be a concern from literature reports due to possible side effects (page 1263, Introduction). Wang address this the problem of polymeric surfactant by introducing a surfactant-free method to prepare PLGA nanoparticles by double-emulsion-solvent evaporation method by using sucrose as the stabilizer of the exterior aqueous phase to prevent aggregation of PLGA nanoparticles during formulation process (page 1263, Introduction; pages 1264-1266).
It would have been obvious to one of ordinary skill in the art to formulate the PLGA nanoparticles of Kreuter and Chitkara without the use of surfactant by replacing the surfactant (PVA) in process of producing the PLGA nanoparticle with sucrose, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Wang provided the guidance to do so by teaching the method to prepare PLGA nanoparticles by double-emulsion-solvent evaporation method of Kreuter and Chitkara can be modified such that the PLGA nanoparticle can be produce without the use of surfactant such as PVA by replacing the PVA in the outer aqueous phase with sucrose, and such replacement provides a surfactant-free surfactant free-formulation of PLGA nanoparticles in which the sucrose does the same function as the PVA to stabilize the exterior aqueous phase and prevent aggregation of PLGA nanoparticles during formulation process. Wang further teaches that this surfactant-free method not only produce PLGA nanoparticles that is less toxic, but also maintains the high encapsulation efficiency (Wang: page 1263, Introduction; page 1266). Thus, an ordinary artisan knowing the drawback of PVA surfactant and seeking to produce PLGA nanoparticles of Kreuter and Chitkara that is less toxic and more biocompatible, yet maintains high encapsulation efficiency, would have looked to replacing the PVA with sucrose as the stabilizer in the outer aqueous phase of the nanoparticles preparation of Kreuter and Chitkara, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding the polymeric nanoparticle is formed in the presence of a polar aqueous solution containing phosphate, bicarbonate, Tris or a combination thereof, of claims 1 and 27, Wu teaches the preparation of a high negatively charged carboxylated PLGA nanoparticles using the w/o/w emulsion process in which a base such as sodium bicarbonate is used to adjust pH of the aqueous solution such that it promotes ionization of the PLGA polymer (Abstract, [0005]-[0010], [0017]-[0021], [0025], [0030]-[0036], [0060], [0064]-[0066], [0071], [0080], [0084], [0087] and [0140]). Wu teaches the high negatively charged carboxylated PLGA nanoparticles is more biocompatible and safer for use on humans and animals, as well as, enhanced therapeutic properties ([0005] and [0006]).
It would have been obvious to one of ordinary skill in art to modify the process of producing the PLGA nanoparticles of Kreuter and Chitkara by including a base such as sodium bicarbonate to the PLGA solution so as produce a high negatively charged carboxylated PLGA nanoparticles, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Wu provided the guidance to do so by teaching that a base such as sodium bicarbonate can be added to PLGA solution during the process of producing the PLGA nanoparticles of Kreuter and Chitkara so as to produce high negatively charged carboxylated PLGA nanoparticles that is more biocompatible and safer for use on humans and animals. Thus, ordinary artisan seeking to produce a high negatively charged carboxylated PLGA nanoparticles that is more biocompatible and safer for use on humans and animals, as well as, enhanced therapeutic properties, would have looked to modify the process of producing the PLGA nanoparticles of Kreuter and Chitkara by including a base such as sodium bicarbonate to the PLGA solution, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claim 15, as discussed above, Kreuter and Chitkara teaches the structural limitations of a polymeric nanoparticle comprising a polymeric shell formed of a polymer containing a non-polar segment and a polar terminal group (i.e., PLGA-COOH) that impermeable to water and an aqueous core containing a hydrophilic drug/compound, and thus, the claimed property of “the polymeric nanoparticle has an osmotic resistance of 840 mOsm/kg or higher” would have been implicit in the structurally similar polymeric nanoparticle of Kreuter and Chitkara. It is noted that [w]here the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
Regarding claim 16, Kreuter teaches the hydrophilic therapeutic agent is small molecule drug or diagnostic agent ([0043]-[0045] and [0107]-[0134]).
Regarding claims 17 and 18, Kreuter teaches the hydrophilic therapeutic agent has a high encapsulation efficiency of greater than 40% ([0107]-[0134]).
Regarding claim 25, as discussed above, Wu provided the guidance to do so by teaching that a base such as sodium bicarbonate can be added to PLGA solution during the process of producing the PLGA nanoparticles of Kreuter and Chitkara so as to produce high negatively charged carboxylated PLGA nanoparticles that is more biocompatible and safer for use on humans and animals.
Regarding claim 26, as discussed above, Kreuter teaches the aqueous core contains a hydrophilic therapeutic agent.
Regarding claim 28, as discussed above, Wu provided the guidance to do so by teaching that a base such as sodium bicarbonate can be added to PLGA solution during the process of producing the PLGA nanoparticles of Kreuter and Chitkara so as to produce high negatively charged carboxylated PLGA nanoparticles that is more biocompatible and safer for use on humans and animals.
Regarding claim 29, as discussed above, Kreuter teaches the polymer is solubilized in an organic solvent such as dichloromethane or chloroform ([0082] and [0095]-[0096]).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant's invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 5 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kreuter et al (22 October 2009; US 2009/0263491 A1) in view of Chitkara et al (Pharm Res., 2013, 30: 2396-2409), Wang et al (AAPS PharmSciTech, December 2009, 10(4): 1263-1267), and Wu (US 2016/0310426 A1; PCT filed date: 4 December 2013), as applied to claim 1 above, and further in view of Lien et al (8 February 2007; US 2007/0031504 A1; previously cited).
The polymeric nanoparticle of claim 1 is discussed and said discussion are incorporated herein in its entirety.
Kreuter, Chitkara, Wang and Wu do not expressly teach the diameter of the core of claims 5 and 6.
Regarding claims 5 and 6, Lien teaches polymeric nanocapsules (nanoparticles) having a thin outer hydrophobic shell and an inner liquid core, wherein the liquid core can be optimized such the total mass of the liquid core in the nanoparticles greater 80% by weight and Lien showed the diameter of the liquid core relative to the shell being greater than 80% that of the outer diameter (shell) of the nanoparticle ([0006], [0007], [0015], [0024], [0028], [0031]-[0034] and Figure 1).
It would have been obvious to one of ordinary skill in the art to optimize the aqueous core in the polymeric nanoparticle of Kreuter in view of Chitkara, Wang and Wu such that the aqueous core has a diameter greater than 70% or 80% that of the outer diameter of the polymeric nanoparticle, per guidance from Lien, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do because Lien provide the guidance and showed that the diameter of the aqueous core can be optimize to have a diameter of greater than 80% that of the shell of the nanoparticles by teaching that total mass of the core can be as high as 95% weight percent (Lien: [0032] and Figure 1). Thus, an ordinary artisan provided the guidance from Lien, would have reasonable expectation that the aqueous core of Kreuter and Chitkara can be made to have a diameter of greater than 70 or 80% that of the outer coating (shell) of the polymeric nanoparticle because Fig 1 of Chitkara relatively showed that the diameter of the aqueous core is much greater than the outer diameter of the polymeric nanoparticle (Chitkara: page 2401).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant's invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kreuter et al (22 October 2009; US 2009/0263491 A1) in view of Chitkara et al (Pharm Res., 2013, 30: 2396-2409), Wang et al (AAPS PharmSciTech, December 2009, 10(4): 1263-1267), and Wu (US 2016/0310426 A1; PCT filed date: 4 December 2013), as applied to claims 1 and 16 above, and further in view of Jiang et al (21 August 2014; US 2014/0235803 A1; previously cited).
The polymeric nanoparticle of claims 1 and 16 are discussed above, and said discussion are incorporated herein in its entirety.
Kreuter, Chitkara, Wang and Wu do not expressly teach the bioactive agent of claim 20.
Regarding claim 19, Jiang teaches polymeric nanoparticles, wherein the polymeric nanoparticles encapsulates any therapeutic agent including nucleic acids such as siRNA using the emulsification technique (abstract; [0092]-[0096], [0182]-[0189], [0193], [0208], [0214]; claims 1-4). Jiang teaches the resultant nanoparticles provide high drug-loading capacity ([0182] and [0214]).
It would also have been obvious to one of ordinary skill in the art to incorporate nucleic acid such as siRNA as the therapeutic agent encapsulated in the polymeric nanoparticle of Kreuter in view of Chitkara, Wang and Wu, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Jiang provided the guidance for incorporating nucleic acid such as siRNA as the drug that can be encapsulated in a polymeric nanoparticle, and Kreuter and Chitkara have indicated that any hydrophilic drug is suitable for incorporating as the drug in the polymeric nanoparticle (Kreuter: [0042]-[0045]; Chitkara: Abstract and page 2408). Thus, it would have been merely simple substitution of one known therapeutic agent suitable for delivery from polymeric nanoparticle for another to achieve a predictable polymeric nanoparticle that provide delivery or release of the therapeutic agent to the desired environment. As such, [t]he selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant's invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 10/23/2025 have been fully considered but they are not persuasive.
Below is the Examiner’s response to Applicant’s arguments as they pertain to the pending 103 rejections.
Applicant argues that Kreuter does not teach or suggest a polymeric nanoparticle free of surfactant, the polymeric nanoparticles formed in the presence of an aqueous solution containing a phosphate, a bicarbonate, a Tris or a combination thereof, or a polymeric nanoparticle containing one or more aqueous cores, as required by claim 1. (Remarks, pages 7-8).
In response, the Examiner disagrees. It is noted that the polymeric nanoparticle containing one or more aqueous cores was taught by Kreuter. See 103 rejection, page 5 of this office action.
With respect to the polymeric nanoparticle being free of surfactant as recited in claim 1, as discussed above in the pending 103 rejection, Wang provided the guidance to do so by teaching the method to prepare PLGA nanoparticles by double-emulsion-solvent evaporation method of Kreuter and Chitkara can be modified such that the PLGA nanoparticle can be produce without the use of surfactant such as PVA by replacing the PVA in the outer aqueous phase with sucrose, and such replacement provides a surfactant-free surfactant free-formulation of PLGA nanoparticles in which the sucrose does the same function as the PVA to stabilize the exterior aqueous phase and prevent aggregation of PLGA nanoparticles during formulation process. See 103 rejection, pages 6-7 of this office action.
With respect to the polymeric nanoparticles formed in the presence of an aqueous solution containing a phosphate, a bicarbonate, a Tris or a combination thereof of claim1, as discussed above in the pending 103 rejection, Wu provided the guidance for modifying the process of producing the PLGA nanoparticles of Kreuter and Chitkara by including a base such as sodium bicarbonate to the PLGA solution so as produce a high negatively charged carboxylated PLGA nanoparticles. See 103 rejection, pages 8-9 of this office action.
Accordingly, the polymeric nanoparticle of claim 1 remained to be render obvious by the combined teachings of Kreuter, Chitkara, Wang, and Wu in the pending 103 rejection as set forth in this office action. See 103 rejection, pages 5-9 of this office action.
Applicant argues by alleging that the double emulsion technique does not necessarily yield polymeric nanoparticles containing an aqueous core. Applicant alleges that “the presence of an aqueous core cannot be assumed simply because a double emulsion process is used.” Applicant provided Declarations from Dr. Che-Ming Jack Hu under 37 CRF 1.132 and evidence provided therein (“Exhibit A” and “Exhibit B”) showing that “traditional double emulsion technique does not produce polymeric nanoparticles having an aqueous core.” Applicant alleges that the Declaration showed that “a double emulsion process without an anionic polymer such as PLGA-COOH or a modulator such as a phosphate, a bicarbonate, a Tris or a combination thereof fails to yield the nanoparticle of amended claim 1.” Applicant goes on to allege that “[t]he three sets of data described in the Declaration consistently demonstrate that a double emulsion process without an anionic polymer such as PLGA-COOH or a modulator recited in amended claim 1 does not produce a stable nanoparticle having an aqueous core. See the Declaration, paragraphs 6-9.” (Remarks, page 8).
In response, the Examiner disagrees. The Declaration from Dr. Che-Ming Jack Hu (hereafter “Hu Declaration”) under 37 CRF 1.132 filed 10/23/2025 is considered, but found insufficient to obviate the pending 103 rejections as set forth in this office action for the reasons discussed below.
First, it is noted that the Hu Declaration at paragraph 6 declared that on page 12 (right column) of Exhibit A (Tsai et al reference) the preparation of M2e Nanoshell was prepared using first and second aqueous solutions containing a phosphate, i.e., sodium phosphate. However, this statement is misplaced because the M2e Nanoshell preparation on page 12, right column of the Tsai reference used NaHCO3 (sodium bicarbonate) in both the first and second solutions, and not sodium phosphate as declared by the Hu Declaration. Furthermore, at paragraph 7 of the Hu Declaration, it was declared that “similar results were obtained with a bicarbonate and siRNA.” However, dissimilar to Exhibit A attached with the Hu Declaration, no objective evidence was provided that showed “similar results were obtained with a bicarbonate and siRNA.” Thus, no determination can be made whether “similar results” as shown in the Tsai reference were achieved from the declaration made at paragraph 7 of the Hu Declaration, as no objective evidence was provided.
Second, claims 1 and 27 are not commensurate in scope with the M2e Nanoshell preparation on page 12 (right column) of Exhibit A (Tsai et al reference). The polymeric nanoparticle of claim 1 and the product by process claim 27 are much broader than the nanoparticle prepared in Exhibit A. It is noted that the nanoparticle in Exhibit A used 200 mM of NaHCO3 in the inner aqueous phase and 10 mM of NaHCO3 in the outer aqueous phase. Neither claim 1 nor claim 27 recites 200 mM of NaHCO3 in the inner aqueous phase or 10 mM of NaHCO3 in the outer aqueous phase. Claims 1 and 27 are drawn to generically polar aqueous solution(s) containing broadly any phosphate, any bicarbonate, any Tris, or a combination thereof. While FIG. 1 in Exhibit B used 200 mM Tris-HCL, 200 mM sodium bicarbonate, or 200 mM sodium phosphate, the concentration of 200 mM nor the particularly buffer (Tris-HCL, sodium bicarbonate, and sodium phosphate) are captured in claim 1 or claim 27. There is no predictability if 2 mM potassium phosphate (which reads on the generically claimed “a phosphate”) would behave in the same manner when used as the buffer in the polar aqueous solution to achieve the same results shown in Exhibit A or Exhibit B of Applicant’s Hu Declaration.
Furthermore, carboxyl-terminated, 50:50 PLGA having a molecular weight (Mw) 7000-17000 was used as the polymer in Exhibit A. However, claims 1 and 27 are drawn to broadly a polymer containing a non-polar segment being poly(lactic-co-glycolic acid) and a polar terminal group being a carboxylic acid with no specificity to the ratio of PLGA or the molecular weight of PLGA. Thus, there is no predictability if a 75:25 PLGA having a molecular weight 66-107 kDa would have behave in the same manner to achieve the same results as shown in Exhibit A or Exhibit B of Applicant’s Hu Declaration.
In addition, in Exhibit A, M2e peptides and cdGMP were used as the active ingredients in the aqueous core. Claims 1 and 27 are drawn to generically any “bioactive agent” including hydrophobic active ingredients. There is no predictability if for example vitamin C or vitamin E which reads on the claimed “bioactive agent” would be stabilized in the aqueous core that is encapsulated in the polymer containing a non-polar segment being poly(lactic-co-glycolic acid) and a polar terminal group being a carboxylic acid of the claimed polymeric nanoparticle.
As such, MPEP §716.02 states: [w]hether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100°C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110°C and 130°C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60°C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100°C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.).
Lastly, while Declarant alleged in the Hu Declaration that “a typical double emulsion process without the anionic polymer PLGA-COOH or a modulator does not produce a stable nanoparticle having an aqueous core capable of efficient encapsulation of an agent,” the comparative evidence shown in Exhibits A and B from the Hu Declaration are specific to double emulsion preparation shown in Exhibit A and thus, cannot be used to extrapolate that all double emulsion preparations used in preparing polymeric nanoparticles including Kreuter and Chitkara “do[es] not produce a stable nanoparticle having an aqueous core capable of efficient encapsulation of an agent.” This is because Applicant’s comparative evidence did not show the PLGA nanoparticles prepared by the double emulsion preparation of Kreuter or Chitkara “do[es] not produce a stable nanoparticle having an aqueous core capable of efficient encapsulation of an agent.”
As discussed in the pending 103 rejection, at least paragraphs [0065], [0073], [0110], [0112], [0114]-[0118], [0120], [0122] and [0126] of Kreuter disclosed that the polymeric nanoparticles were prepared by double emulsion technique in which doxorubicin hydrochloride (HCl) (a hydrophilic drug) was dissolved in an aqueous solution. Likewise, Chitkara’s polymer nanoparticles were prepared by double emulsion technique in which Gemcitabine HCl (a hydrophilic drug) was dissolved in an aqueous solution (Chitkara: Abstract; page 2397, right column; page 2398, left column; page 2399 and Table 1; page 2400, right column; page 2401 and Fig. I; pages 2402-2403; page 2406, right column), and Chitkara confirms that the polymer of PLGA from Kreuter used in the double emulsion technique forms the shell that surrounded the hydrophilic core that was formed from Gemcitabine HCl (a hydrophilic drug) dissolved in the aqueous solution (Chitkara: Abstract; page 2397, right column; column 2398, left column; page 2401; Fig. 1b(ii); page 2406). Thus, the core of the polymeric nanoparticle of Kreuter is indeed an aqueous core.
Applicant argues that Chitkara does not cure the deficiencies of Kreuter, as Chitkara “also does not teach or suggest a surfactant-free nanoparticle or a nanoparticle formed in the presence of an aqueous solution containing a phosphate, a bicarbonate, a Tris or a combination thereof.” Applicant further alleges “Chitkara explicitly teaches nanoparticles having a core that is more electron dense than the shell, indicating that the nanoparticles have a solid rather than an aqueous core. See, page 2401, Figure 1 and the left column, first paragraph, lines 5-7; and the Declaration, paragraph 10.” (Remarks, page 8, last paragraph to page 9).
In response, the Examiner disagrees. The pending 103 rejection over independent claim 1 is based on the combined teachings of Kreuter, Chitkara, Wang, and Wu. As discussed in the pending 103 rejection, the combined teachings of Kreuter, Chitkara, Wang, and Wu do teach and render obvious Applicant’s claimed surfactant-free nanoparticle or a nanoparticle formed in the presence of an aqueous solution containing a phosphate, a bicarbonate, a Tris or a combination thereof.” See 103 rejection, pages 5-9 of this office action.
Applicant’s allegation that Chitkara’s nanoparticle does not have an aqueous core. However, as discussed above, it is reiterated that Kreuter taught the claimed polymeric nanoparticle having an aqueous core. As discussed above, at least paragraphs [0065], [0073], [0110], [0112], [0114]-[0118], [0120], [0122] and [0126] of Kreuter disclosed that the polymeric nanoparticles were prepared by double emulsion technique in which doxorubicin hydrochloride (HCl) (a hydrophilic drug) was dissolved in an aqueous solution. Likewise, Chitkara’s polymer nanoparticles were prepared by double emulsion technique in which Gemcitabine HCl (a hydrophilic drug) was dissolved in an aqueous solution (Chitkara: Abstract; page 2397, right column; page 2398, left column; page 2399 and Table 1; page 2400, right column; page 2401 and Fig. I; pages 2402-2403; page 2406, right column), and Chitkara confirms that the polymer of PLGA from Kreuter used in the double emulsion technique forms the shell that surrounded the hydrophilic core that was formed from Gemcitabine HCl (a hydrophilic drug) dissolved in the aqueous solution (Chitkara: Abstract; page 2397, right column; column 2398, left column; page 2401; Fig. 1b(ii); page 2406). Thus, the core of the polymeric nanoparticle of Kreuter is indeed an aqueous core.
As a result, for at least the reasons discussed above, claims 1, 5-6, 15-19, and 25-29 remain rejected as being obvious and unpatentable over the combined teachings of the cited prior arts in the pending 103 rejections as set forth in this office action.
Conclusion
No claim is 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.
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/DOAN T PHAN/Primary Examiner, Art Unit 1613