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 .
Claim Status
Applicants’ amendments and arguments filed 09/17/2025 have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claims 1-13, 17, 21, and 28 are canceled.
Claims 25-27 are withdrawn.
Claims 14, 19, 23, 25-27, and 30 are amended.
Claims 14-16, 18-20, 22-24, and 29-30 are examined on the merits.
Election/Restrictions
Claims 26 and 27 are now dependent upon claim 25 which is directed to an unelected group, Group 2 - claim 25. Therefore, claims 25-27 are not considered for being directed towards an unelected group.
Claim Interpretation
In regards to claim 14, as to the limitation of ‘provided that in an in vitro assay, the delivery system prevents release of more than 5 wt.-% of the one or more anticancer agents of component (a.2) for at least 2 hours into a liquid medium that does not contain the one or more anticancer agents of component (a.2), and the highest release rate of the one or more chemotherapeutic agents from the delivery system in the in vitro assay is not observed before 8 hours, wherein in the in vitro assay the delivery system is enveloped in a membrane when added into the liquid medium, the membrane being permeable to the liquid medium and to the one or more anticancer agents of component (a.2) but not permeable to other constituents of the delivery system’, it is noted that the instant claims are a method of treating cancer with an active delivery composition claims and future intended use, such as in an in vitro assay is not given patentable weight. Thus any method of treating cancer in a human subject comprising directly administering into the human subject’s abdomen or thorax an active substance delivery system using an assisting tool selected from a microneedle, a spray device, or an angio-injector and the composition comprising (a.1) 50-98% of one or more polymers selected from the group consisting of poly(lactic-co-glycolic acid) (PLGA), poly(lactide), poly(lactide-co-glycolide), poly(isobutylcyanoacrylate), poly(isohexylcyanoacrylate), poly(n-butylcyanoacrylate) poly(acrylate), poly(methacrylate), chitosan, alginate, gelatin, albumin, poly(methacrylate), poly(e-caprolactone), polylactic acid, poly(b hydroxyl butyrate), ethyl cellulose, polystyrene, poly(vinyl pyridine), poly(alkyl methacrylate), and poly(alkyl cyanoacrylate); (a.2) 0.25 to 20% of one or more anti-cancer agents; (a.5) 0.5 to 20% of one of more stabilizers wherein the average particle is from 100-5000nm, will meet this limitation. Further with regard to claim 14, the ‘provided that’ limitations of this claim is considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (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.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).).
Claims 14 and 25 recite the terms “optional” and “optionally”, which is interpreted by examiner to mean any component following these terms is not a required claim limitation.
New Rejections Necessitated by Claim Amendments
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.
Claims 14-16, 18-20, 22-23, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Au et al. (WO2004089291A2, published 10/21/2004, hereafter Au) in view of Hetzel et al. (US9511197B2, published 12/06/2016, hereafter Hetzel), and in view of Yueneng Yi (CN102232926A, found within ISR, published 11/09/2011, English google translate used, hereafter, Yi).
Au teaches administering drug-loaded gelatin and poly(lactide-co-glycolide) (PLGA) nanoparticles and microparticles to target drug delivery to tumors in the peritoneal cavity (abstract), wherein the invention is administered to mammals, e.g., humans having a disorder characterized by aberrant cell growth, e.g., a cancer (page 8, line 23-33; according to the claim limitations of the instant claim 14). Au also teaches one of the agents formulated in the gelatin and PLGA (i.e., natural and/or synthetic polymers) particles is paclitaxel (i.e., chemotherapeutic agent) (page 4, lines 22-23; according to the claim limitations of the instant claims 14 and 16). Claim 8 of Au further teaches the therapeutic agent is one or more of paclitaxel or doxorubicin (according to the claim limitations of the instant claim 16). Au teaches that gelatin refers to a denatured protein collagen in which the aggregates are stabilized by cross-linking the protein chains(page 10, lines 20-22; according to the claim limitations of the instant claim 14). Au further teaches that wherein said one or more of nanoparticles or microparticles are coated with a bioadhesive (claim 57) wherein the bioadhesive can be poly(lysine) polyacrylic acid polymers, polysaccharides, etc. (i.e., polymers or block co-polymers) (page 11, lines 2-7; according to the claim limitations of the instant claim 14). Au continues to teach nanoparticles refers to particles of about 0.1nm to about 1µm (page 9, lines 5-6; according to the claim limitations of the instant claim 14). Au further teaches in table 1 the actual loading % of paclitaxel in the range of 1.81-4.25% (i.e., chemotherapeutic agent) (page 29, table 1; according to the claim limitations of the instant claims 14 and 16). Au teaches a slow-release formulation of a tumor therapeutic agent wherein the drug is delivered to a site of interest for a sustained period of time and includes formulations which maintain release of its drug contents preferably for several day, several weeks or longer (page 9, lines 24-27; according to the claim limitations of the instant claims 18 and 30). Au teaches the dose were 120mg/kg paclitaxel-equivalents for the microparticles (page 35, line 20; according to the claim limitations of the instant claim 19). Au teaches that the microparticles are used to treat multiple types of cancer originate from organs located within the peritoneal cavity e.g. pancreatic, liver, colorectal, and ovarian, lung cancer, and then further teaches the microparticles treat multiple pelvic and abdominal surfaces to include intestinal mesenteries, bladder, omentum, diaphragm, lymph nodes, and liver (page 1, lines 25-32; according to the claim limitations of the instant claims 15 and 20). Au teaches the particles also can be combinations of two or more types of particles with at least one type releasing the drug rapidly while the remaining types release the drug more slowly (page 4, lines 8-10; according to the claim limitations of the instant claims 22-23). Au teaches the microparticles consisted of three formulations, one that released paclitaxel rapidly (Batch 8, 70.5% in 1 day) and two that released paclitaxel slowly (Batch 6, 72.6%o in 49 days, and Batch 4, 28.7% in 49 days) (page 35, lines 23-25; according to the claim limitations of the instant claim 29). Au teaches it is advantageous to add a release enhancer such as Tween 20 or Tween 80 in order to achieve a release rate as desired for the application (claim 73 and page 15, lines 18-20; according to the claim limitations of the instant claim 14). Au teaches Example 7, in which gelatin was dissolved in 10 ml water containing 2% Tween 20 then to this solution, 2ml of sodium sulfate solution, then 5.5-6ml of sodium sulfate solution, then 1ml water, then 0.4ml glutaraldehyde, and then 5ml of sodium metabisulfite solution (page 37, lines 5-18; according to the claim limitations of the instant claim 14). Lastly, Au teaches that the fast release the composition showed a drug release rate of ~70% in a day then the slow release demonstrates an initial burst drug release rate of ~5% in the first day followed by a slower release yielding a total cumulative release of 30% in seven weeks (page 15, lines 21-25 and 32-35 and page 16 lines 1-2; according to the claim limitations of the instant claim 14).
Although Au teaches administering into the abdominal cavity, it fails to teach administration using a microneedle, angio-injector, or spray device, such as the elected species of laparoscopic nebulizer. Additionally, although Au teaches PLGA being the basis of the particle, it fails to teach an exact concentration of PLGA as in the instant claim 14. Furthermore, although Au teaches the addition of gelatin, Tween 20 (also known as polysorbate 20), and Tween 80 (also known as polysorbate 80), it fails to teach the exact concentration range of a stabilizer as in instant claim 14.
Hetzel teaches a surgical laparoscopy device for applying a substance in a hollow space of a body cavity, the device comprising a trocar system with a trocar sleeve, wherein the trocar system comprises a gas connection to which an insufflation gas-supply line is connectable and a nozzle system which forms a lumen and is configured to apply substance (X) as an aerosol in the hollow space(title and claim 1; according to the claim limitations of the instant claim 14). Hetzel further teaches this device is well known to treat disease in the abdomen and thorax (column 1, lines 18-22; according to the claim limitations of the instant claim 14). Hetzel teaches the aerosol has medically active nanoparticles (column 2, line 26; according to the claim limitation of the instant claim 14). Hetzel teaches the substance may include particular drugs suitable for chemotherapy, such as doxorubicin (column 5, lines 4-6; according to the claim limitations of the instant claim 14). Lastly, in a further embodiment a pump, in particular a micro-pump, which is connected to the nozzle system in a fluid conductive manner so that substance (X) is atomized to a mist-like aerosol (columns 4-5, lines 63-67 and 1-2 respectively; according to the claim limitations of the instant claim 14).
Yi teaches a nanoparticle for oral administration containing paclitaxel, a polymer (specifically lactide-glycolide copolymer (PLGA)), and a membrane modification material (claim 1; according to the claim limitations of the instant claims 14 and 16). Furthermore, Yi teaches that paclitaxel also known as Taxol is an FDA approved anti-cancer drug (description-background technique; according to the claim limitations of the instant claims 14 and 16). Yi teaches the concentration of paclitaxel to be 1 parts by weight which calculates to a range of 1.4-8.3% (page 2, last paragraph; according to the claim limitations of the instant claim 14). Yi teaches the concentration of the polymer PLGA to be 8 parts by weight which calculates to a range of 11.6-66.6% (page 2, last paragraph; according to the claim limitations of the instant claim 14). Yi describes that the membrane modification material is used to improve the stability of the nanoparticles (page 3, paragraph (3)); according to the claim limitations of the instant claim 14). Furthermore, Yi teaches the concentration of the membrane modification material to be 1-20 parts by weight which calculates to a range of 2-64%(page 2, last paragraph; according to the claim limitations of the instant claim 14). Yi teaches the membrane modification material can be polyethylene glycol and chitosan (page 3, paragraph 2; according to the claim limitations of the instant claim 14). Yi teaches the membrane modifying material is coated on the surface of the PLGA (abstract; according to the claim limitations of the instant claim 14). Yi further outlines the desired concentration of the membrane modification material to be 1g/100mL to 5g/100ml or 1-5% (page 2, last paragraph; according to the claim limitations of the instant claim 14). Yi teaches a particle size of 100-300nm (description-background technique; according to the claim limitations of the instant claim 14). Yi teaches that paclitaxel has low bioavailability orally and the drug is mostly administered by injection presently (page 2, paragraph 8; according to the claim limitations of the instant claim 14). Yi teaches paclitaxel can be used with injection to treat ovarian cancer, gastric cancer, rectal cancer, and more (page 2, paragraph 11; according to the claim limitations of the instant claims 14-16 and 20). Lastly, Yi teaches that the preparation of chitosan and prepared medicine has tangible slow release apoptosis promoting effect to tumor cells (page 2, paragraph 8; according to the claim limitations of the instant claim 14). Furthermore, Yi teaches the addition of a surfactant, specifically polysorbate 80, at a ratio of 1 part paclitaxel to 1-20 parts surfactant (claim 1; according to the claim limitations of the instant claim 14). Lastly, Yi teaches that paclitaxel has poor oral bioavailability and is mostly administered by injection presently (page 2, paragraph 8; according to the claim limitations of the instant claim 14).
It would be obvious to one skilled in the art before the effective filing date of the claimed invention to claim the method of administering into a humans abdomen or thorax a particle comprising PLGA, paclitaxel, and gelatin as outline by Au with the ready for improvement with the known technique of using a laparoscopic device to aerosolize and insufflate a chemotherapeutic drug particle into the abdomen or thorax of a patient as outlined by Hetzel and with the known technique of adjusting the concentrations of stabilizer and PLGA as outlined by Yi . Adding the forementioned step and adjusting the concentrations in a method of administering a paclitaxel particle to the abdomen of a human as claimed by instant claim 14 would yield predictable results thus making them of obviousness as modification of a known product with a known technique is within the purview of the skilled artisan
Claims 24 is rejected under 35 U.S.C. 103 as being unpatentable over Au et al. (WO2004089291A2, published 10/21/2004, hereafter Au) in view of Hetzel et al. (US9511197B2, published 12/06/2016, hereafter Hetzel), in view of Yueneng Yi (CN102232926A, found within ISR, published 11/09/2011, English google translate used, hereafter, Yi), and in view of Liggins et al. (Liggins, R. T., D’Amours, S., Demetrick, J. S., Machan, L. S., & Burt, H. M. (2000). Paclitaxel loaded poly(l-lactic acid) microspheres for the prevention of intraperitoneal carcinomatosis after a surgical repair and tumor cell spill. Biomaterials, 21(19), 1959–1969. https://doi.org/10.1016/s0142-9612(00)00080-6, hereafter Liggins).
As outlined above, Au in view of Hetzel and Yi Au teaches administering drug-loaded gelatin and poly(lactide-co-glycolide) (PLGA) nanoparticles and microparticles to target drug delivery to tumors in the peritoneal cavity (abstract) using an aerosolizing laparoscopic device. However, Au in view of Hetzel and Yi does not teach wherein the method prevents or delays cancer recurrence after a surgical tumor removal. However this deficiency is cured by Liggins et al.
In the analogous art of a release delivery system, Liggins teaches a controlled release delivery system for paclitaxel was developed using poly(l-lactic acid) to provide local delivery to the peritoneal cavity (abstract). Liggins also teaches that the delivery of chemotherapeutic agents using polymeric microspheres has become a popular area of research because of the possibilities of achieving controlled release and of localizing the delivery of cytotoxic agents (page 1, third paragraph of introduction section). Liggins further teaches that paclitaxel-loaded microspheres may offer an effective therapy for the prevention of intraperitoneal carcinomatosis after a surgical repair with a tumor cell spill. The advantages of an intraperitoneal microsphere formulation of paclitaxel are as follows. Reduced systemic exposure of paclitaxel is expected due to intraperitoneal administration, localized delivery and the slow clearance of the drug from the peritoneal cavity. Prolonged exposure, which improves the efficacy of paclitaxel is achieved due to retention of microspheres at the site and prolonged release of the drug from the microspheres (page 9, Discussion section last paragraph).
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 have a method which prevents or delays cancer recurrence after a surgical tumor removal of Liggins et al in the method of treating cancer as outlined by Au in view of Yi and Hetzel. Au in view of Yi and Hetzel teaches paclitaxel loaded nanoparticles administered intraperitoneally to the peritoneal cavity. One would have understood in view of Liggins that that paclitaxel-loaded microspheres may offer an effective therapy for the prevention of intraperitoneal carcinomatosis after a surgical repair with a tumor cell spill. It would have been obvious to one of ordinary skill in the art to have a method which prevents or delays cancer recurrence after a surgical tumor removal in Au in view of Yi and Hetzel’s method of treating cancer because Liggins teaches that having a paclitaxel-loaded polymer microsphere helps in the prevention intraperitoneal carcinomatosis after a surgical repair.
Response to Applicant’s Arguments
Applicant’s arguments filed o 09/17/2025 have been considered by the examiner.
In regards to Applicant’s argument against second “35 USC § 112(d)” which Examiner interprets to mean “35 USC § 103” as Applicant references the 35 USC § 103 rejections of record below the title, Applicant first argues that Yi cannot be combined with Au, Hetzel, and Liggins because Yi is directed towards oral dosage forms while the remaining references are concerned with direct administration into the abdominal or thoracic cavity. Furthermore, Applicant argues the present claims are directed towards preventing release of more than 5wt% of the anticancer agent for at least 2 hours in vitro and does not reach its highest release rate before 8 hours. Applicant argues that Au teaches the opposite providing an example that Au releases at both a rapid and slow rate, while providing example 7 from Au’s disclosure.
In response to applicant's arguments against the references individually, specifically Yi and then AU, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In regards to Applicant’s argument that Yi cannot be combined with Au, Hetzel, and Liggins, it is noted that Yi is a secondary reference solely used to render the deficiencies of Au, specifically to adjust the concentrations of Au. Yi is directed towards administering a paclitaxel drug as an anti-cancer drug with the same components as Au (i.e. PLGA, polysorbate, etc.) (see above 103 rejection). Additionally, as Applicant mentions, Yi teaches that paclitaxel has poor oral bioavailability and is mostly administered by injection presently (page 2, paragraph 8) thus further providing motivation as Yi notes this technology is commonly used in injection methods.
In response to Applicant’s argument that Au does not teach the same release rate as the instant claims, it is first noted that the ‘provided that’ assay is both intended use and a result of the instantly claimed method as outlined in the claim interpretation above. Further, this is outlined by In re Best, 562 F.2d 1252, 1255 (ССРА 1977) which decided “Where, as here, the claimed and prior art products are identical or substantially identical,... the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product.... [The] fairness [of the burden-shifting] is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products.” As outlined in the 103 rejection above, Au in view Hetzel in view of Yi teaches the same composition with the same components (PLGA, paclitaxel, and stabilizer at the desired particle size), in the same or overlapping amounts with the ‘optimizing’ of the amount of PLGA, and method of delivering the composition to treat the cancer to include the instant claimed cancers. Therefore, the composition and method of Au in view of Hetzel in view of Yi would necessarily have the same or a similar delivery profile as the instantly claimed invention. Therefore, the burden falls on Applicant to demonstrate that ‘optimizing’ the amounts of PLGA and the stabilizer (Tween 20) would result in a delivery profile that differs from the instantly claimed.
Overall, the examiner is not persuaded by Applicant’s argument and the rejections of record are updated to account for amendments.
In regards to Applicant’s argument against the Double Patenting rejections, Applicant states that upon allowance, Applicant will assess the need for terminal disclaimer.
Applicant’s response fails to address the rejections of record or provide any reasoning for the rejections to be withdrawn. However, it light of the copending applications being abandoned, the rejections of record have been withdrawn.
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.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/A.N.I./ Examiner, Art Unit 1611