DETAILED ACTION
RESPONSE TO AMENDMENT
1. Receipt of Applicants’ amendments and arguments/remarks filed 3/6/2026 are acknowledged.
INFORMATION DISCLOSURE STATEMENT
2. No new Information Disclosure Statement has been submitted for review.
WITHDRAWN REJECTIONS
3. Rejections not reiterated from previous Office Actions are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections- 35 USC § 103
4. 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 12-16 and 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (US 20160220490), Carnevale et al. “Prostatic Artery Embolization as a Primary Treatment for Benign Prostatic Hyperplasia: Preliminary Results in Two Patients”, Altschul et al. (US Patent 9,314,473), Lennernans et al. (US 20080286205) and Hamisheckhar et al. “Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia”.
Zeng et al. (US 20160220490) (hereinafter Zeng et al.) disclose microspheres and embolic compositions to embolize and optionally deliver drug to any structure or region in which embolization and drug therapy is desired. They are used to embolize the prostate (para 0019). The PLGA microspheres may be used to embolize part or all of the prostate in order to treat benign prostatic hyperplasia (para 0019). The molar ratio of the PLGA can be 50:50 (claim 1 and paras 0023, 0025). The microspheres range from 50 to 250 micron (para 0023). This range overlaps with the claimed d90 of 40-500 microns because all the microspheres are the size of Zeng et al. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Zeng et al. disclose the PLGA microspheres degrade over intervals ranging from 1 month to 1 year and the drug is eluted ranging from 2-4 weeks to one or more months (para 0007). Zeng et al. disclose delivery to patients while “humans” is not mentioned it is obvious to one of ordinary skill in the art that the patient may be human given that the same conditions can be treated such as prostatic benign hyperplasia. Zeng et al. disclose microspheres and embolic compositions are used to embolize and optionally delivery drug to any structure or region in which embolization and drug therapy is desired. PLGA microspheres without any drug loading may be used to embolize part or all of the prostate for treating benign prostatic hyperplasia (para 0019). The microspheres are preferably loaded with a lipophilic drug and while the reference discloses paclitaxel as preferred and not flutamide (para 0007), Hamisheckhar et al. “Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia” demonstrates that flutamide is a lipophilic drug (see page 849-Entrapment efficiency and loading efficiency).
Zheng et al. does not specifically state “introducing into the prostatic artery” however, it is heavily implied that it would be given that way since benign prostate hyperplasia is disclosed as being treated via embolization. Furthermore, Carnevale et al. “Prostatic Artery Embolization as a Primary Treatment for Benign Prostatic Hyperplasia: Preliminary Results in Two Patients” disclose various medications such as 5 α reductase inhibitors can decrease the severity of the symptoms of secondary benign prostatic hyperplasia (abstract and discussion) . The abstract teaches that two patients with benign prostatic hyperplasia were successfully treated by prostate artery embolization. The patients include a 67 year old man and 68 year old man (humans). Given that Zeng et al. disclose treating benign prostatic hyperplasia via embolization, it would be obvious to one of ordinary skill in the art to delivery to the prostatic artery in order to treat benign prostate hyperplasia as taught by Carnevale.
Zheng et al. does not specifically teach flutamide. Altschul et al. (US Patent 9,314,473) (hereinafter Altschul et al.) disclose androgen receptor antagonist selected from flutamide. The selective androgen receptor antagonists have utility for treatment of conditions including benign prostatic hyperplasia. In carrying out the method of the present invention, the combination of the invention may be administered to mammalian species, such as dogs, cats, humans, etc. and as such may be incorporated in a conventional systemic dosage form, such as a tablet, capsule, elixir or injectable and that the pharmaceutical compositions of the invention may be administered in the dosage forms in single or divided doses of one to four times daily. Altschul et al. disclose tablets of sizes 1 to 2000 mg in total weight.
Lennernans et al. (US 20080286205) (hereinafter Lennernans et al.) disclose flutamide for prostate related diseases (claims 1, 17) and where the dose can be from 100 mg to 2000 mg per day (claim 22). The methods are suitable for treatment of benign prostatic hyperplasia (para 0001 and 0034). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to include lipophilic medications such flutamide in the microsphere compositions of Zeng et al. for the treatment of benign prostatic hyperplasia. One would have been motivated to do so because flutamide is an known lipophilic drug used for treatment of benign prostatic hyperplasia and Zeng et al. disclose any lipophilic drugs can be included with the microspheres. The microspheres on their own are taught to treat benign prostate hyperplasia however, lipophilic drugs may also be incorporated and it would be obvious to one of ordinary skill in the art to select flutamide, a known lipophilic drug, for use in the microspheres as it is known to treat benign prostate hyperplasia as demonstrated by Altschul et al. and Lennernans et al. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In reKerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
5. Claims 12, 17 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (US 20160220490), Carnevale et al. “Prostatic Artery Embolization as a Primary Treatment for Benign Prostatic Hyperplasia: Preliminary Results in Two Patients”, Altschul et al. (US Patent 9,314,473), Lennernans et al. (US 20080286205) and Hamisheckhar et al. “Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia as applied to claims 12-16 and 18-21 above, and further in view of Venkatraman et al. (WO 2018070940) and Makadia et al. “Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Release Drug Delivery Carrier”.
Zeng et al. has been discussed supra and does not disclose PLGA ratio 45:50.
Venkatraman et al. (WO 2018070940) disclose injectable composition for controlled release in humans where the composition contains PLGA ratio of 45:55 (para 0040 and claim 16). The compositions include 5 α-reductase inhibitors to lower dihydrotestosterone levels and alleviate conditions of benign prostatic hyperplasia (para 0005). Makadia et al. “Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Release Drug Delivery Carrier” (hereinafter Makadia et al.) disclose that polymer composition is the most important factor to determine the hydrophilicity and rate of degradation of a delivery matrix which influence the rate of degradation. Increase in glycolic acid percentage in the oligomers accelerates the weight loss of polymer. Subsequently PLGA 65:35 shows faster degradation than PLGA 75:25 and PLGA 75:25 than PLGA 85:15. Thus absolute value of the degradation rate increases with the glycolic acid proportion. The amount of glycolic acid is a critical parameter in tuning the hydrophilicity of the matrix and thus the degradation and drug release rate. Therefore the glycolic acid can be varied to fine tune the degradation rate where the rate increases with the glycolic acid proportion.
Absent any evidence of criticality, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to optimize the PLGA ratio to 45:55. One would have been motivated to do so because these polymers in these ratios are suitable for controlled release of the therapeutic agent and can be fine tuned to the desired degradation rate as the glycolic acid is a critical parameter in tuning the degradation and drug release rate where the rate increases with increased glycolic acid proportion and would decrease with decreased portions.
RESPONSE TO ARGUMENTS
6. Applicants arguments have been fully considered and are not persuasive. Applicants argue that the Examiner has not shown how the Zeng, Carnesvale, Altschul and Lennernas references would have rendered the claimed invention obvious to one of ordinary skill in the art.
In response, the Examiner respectfully disagrees as the obviousness rejection is set forth above. The Examiner maintains the arguments from 2/24/2025.
Zeng et al. disclose PLGA microspheres but did not disclose flutamide. Carnevale et al. and Altschul et al. were relied upon to demonstrate using flutamide for benign prostatic hyperplasia. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to include medications such as 5 α reductase inhibitors (e.g., flutamide) in the microsphere compositions of Zeng et al. for the treatment of benign prostatic hyperplasia. One would have been motivated to do so because flutamide is an known α reductase inhibitor for treatment of benign prostatic hyperplasia and inclusion of α reductase inhibitors can decrease the severity of symptoms of secondary benign prostatic hyperplasia.
Venkatraman et al. was relied upon to teach the ratio of the PLGA. These polymers in these ratios are suitable for controlled release of the therapeutic agent. Applicants have not demonstrated any criticality to the ratio.
CONCLUSION
7. THIS ACTION IS MADE FINAL. 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.
CORRESPONDENCE
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danah Al-awadi whose telephone number is (571) 270-7668. The examiner can normally be reached on 9:00 am - 6:00 pm; M-F (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Danah Al-Awadi/
Primary Examiner, Art Unit 1615