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 . 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.
Election/Restrictions
Applicant’s election of Group I, claims 1-15, in the reply filed on 10/14/2025, is acknowledged. Applicant’s species election of fungal infections caused by Aspergillus spp, claims 16, 17, 19 and 21, in the reply filed on 10/14/2025, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 16-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/14/2025.
Claim Rejections - 35 USC § 103 - Obviousness
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 1, 3-6 and 9-14 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (US 2016/0207956 A1), further in view of Greenlee et al (USP 8,188,085 B2), further in view of Kikuchi et al (US 2012/0058178 A1) and further in view of Peer et al (nature nanotechnology, 2, December 2007, 751-760).
Zhang taught [0004] pharmaceutical compositions comprising pharmaceutically acceptable salts (citrate salts [0145]) of SCY-078, and polymorphs thereof, suitable for injection or intravenous administration (human [claims 46-48; ¶0193]). The compositions comprised pharmaceutically acceptable carriers, including aqueous vehicles (reads on an aqueous phase) [0140].
SCY-078 (reads on the compound of the instant Formula IIa) [0002] has the following chemical structure:
PNG
media_image1.png
260
485
media_image1.png
Greyscale
Zhang incorporated, by reference [0002], Greenlee et al.
Greenlee et al, reproduced below, taught a compound of Formula II, at col 15, lines 32-64. Greenlee reads on the instant Formula IIa.
PNG
media_image2.png
568
453
media_image2.png
Greyscale
Zhang was silent a teaching of an encapsulating unilamellar vesicle comprising phospholipid and cholesterol, as recited in claim 1.
Kikuchi taught [0072, 0169] injectable unilamellar liposomal compositions containing active compounds in the liposome internal phase (reads on an encapsulated compound) [claim 1]. The membrane constituents of the liposome comprised phospholipids (phosphatidyl choline and phosphatidyl glycerol, [0092]) and cholesterol [0095]. As an injection product, the liposome was contained within (dissolved or suspended) an aqueous solvent (distilled water) (reads on unilamellar vesicle hydrated in an aqueous phase) [0166].
Peer taught [Box 1] that nanocarriers offer many advantages over free drugs. They protect the drug from premature degradation; prevent drugs from prematurely interacting with the biological environment; enhance absorption of drugs into a selected tissue; control the pharmacokinetic and drug tissue distribution profile; and, improve intracellular penetration.
It would have been prima facie obvious to one of ordinary skill in the art to have included, within Zhang, an encapsulating liposomal formulation comprised of phospholipid and cholesterol, and hydrated within an aqueous phase, as taught by Kikuchi [0072, 0092, 0095, 0166, 0169, claim 1]. The ordinarily skilled artisan would have been so motivated, because nanocarriers offer many advantages over free drugs, including protecting the drug from premature degradation; preventing drugs from prematurely interacting with the biological environment; enhancing absorption of drugs into a selected tissue; controlling the pharmacokinetic and drug tissue distribution profile; and, improving intracellular penetration, as taught by Peer [Box 1].
The combined teachings of Zhang, Greenlee, Kikuchi and Peer read on claims 1, 5-6 and 12-14.
Claims 3-4 are rendered prima facie obvious because Kikuchi taught a sugar (sucrose) in the external phase of the liposome; the pH of the external phase was 2 to 11. The external phase stabilized the liposome [0036, 0142, 0146]. The motivation to combine Kikuchi with Zhang was previously discussed. Furthermore, and especially concerning the external phase, the skilled artisan would have been motivated to stabilize the liposome, as taught by Kikuchi.
The instant claim 4 recites a pH of 5.0 to 7.0.
Kikuchi taught a pH of 2 to 11. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claims 9-11 are rendered prima facie obvious because Kikuchi’s liposomes were sized 30 to 400 nm [0111]. The motivation to combine Kikuchi with Zhang was previously discussed.
The instant claims 9-11 recite vesicles less than about 150 nm, further limited to less than about 100 nm, or from about 70 to 80 nm.
Kikuchi taught liposomes sized 30 to 400 nm. A prima facie case of obviousness exists because of overlap, as discussed above.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (US 2016/0207956 A1), further in view of Greenlee et al (USP 8,188,085 B2), further in view of Kikuchi et al (US 2012/0058178 A1), further in view of Peer et al (nature nanotechnology, 2, December 2007, 751-760), and further in view of Doyle et al (Doyle, G. R., McCutcheon, J. A. (2015), Clinical procedures for safer patient care. BCcampus. https://opentextbc.ca/clinicalskills/).
The 35 U.S.C. 103 rejection over Zhang, in view of Greenlee, Kikuchi and Peer, was previously described.
Additionally, Zhang taught [0142] effective amounts of the active ingredient.
Zhang incorporated Greenlee, and Greenlee taught exemplary [col 24, lines 12-35] intravenous dosage amounts of 0.001 to 1000 mg/kg (human).
Zhang and Greenlee did not teach the concentration of from about 0.01 to about 50 mg/mL, as recited in claim 2.
Doyle taught that medicine is safely administered, through the direct IV route, to patients (humans, at Checklist 60, pages 488-492) at a maximum volume (fluid) of 20 mL [page 783, 1st and 2nd paragraphs].
Since Zhang referenced Greenlee for exemplary dosage amounts, it would have been prima facie obvious to the ordinarily skilled artisan that Zhang included intravenous dosage amounts of 0.001 to 1000 mg/kg (human), as taught by Greenlee [col 24, lines 12-35].
The skilled artisan would have administered the dosage in a maximum volume of 20 mL fluid, as taught by Doyle et al. The skilled artisan would have been motivated by the desire to safely administer the medicine by the IV route, as taught by Doyle [page 783, 1st and 2nd paragraphs].
The instant claim 2 recites about 0.01 to about 50 mg/mL.
The combined teachings of Zhang and Greenlee, with Doyle taught 0.001 to 1000 mg/kg in a maximum of 20 mL. As such, the combined teachings of the art taught a dosage range, per kg of the patient, of 0.00005 (0.001 ÷ 20 = 0.00005) to 50 (1000 ÷ 20 = 50) mg/mL, which overlaps the instantly claimed dosage of 0.01 to 50 mg/mL. A prima facie case of obviousness exists because of overlap, as discussed above.
Claims 7-8 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (US 2016/0207956 A1), in view of Greenlee et al (USP 8,188,085 B2), further in view of Kikuchi et al (US 2012/0058178 A1), further in view of Peer et al (nature nanotechnology, 2, December 2007, 751-760), further in view of Doyle et al (Doyle, G. R., McCutcheon, J. A. (2015), Clinical procedures for safer patient care. BCcampus. https://opentextbc.ca/clinicalskills/) and further in view of Adler-Moore et al (USP 5,043,107 A).
The 35 U.S.C. 103 rejection over Zhang, Greenlee, Kikuchi, Peer and Doyle was previously discussed. The combined teachings of Zhang and Greenlee, with Doyle taught 0.001 to 1000 mg/kg in a maximum of 20 mL, as previously discussed.
Additionally, Zhang taught, as the active agent, antifungal compounds [0002] and pharmaceutically acceptable salts thereof (e.g., citrate salts [0145]).
Kikuchi taught unilamellar vesicles (previously discussed) comprising [0094] 10-80 mole percent phospholipid (phosphatidylglycerol and phosphatidylcholine) and [0096] 1-60 mol percent cholesterol.
The combined teachings of the prior art were not specific the molar amounts of the active compound, as recited in claims 7-8 and 15.
However, Adler-Moore taught [title] unilamellar vesicles comprising antifungal agents, where the compositions comprised [claims 4, 7, 9] the antifungal compound, at least one phospholipid and cholesterol, in a mole percentage ranging from about 5-15 mole percent of the active agent, about 40-90 mole percent of the phospholipid and about 10-40 mole percent cholesterol.
Since the combined teachings of Zhang and Kikuchi taught unilamellar vesicles comprising antifungal agents, it would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of the art, the active agent at about 5-15 mole percent, as taught by Adler. The ordinarily skilled artisan would have been motivated to form unilamellar vesicles comprising antifungal agents, as taught by Adler-Moore [claims 4, 7 and 9, and at the title].
The instant claim 7 recites about 5 to about 12 mole percent of the active agent; about 50 to about 80 mole percent of the phospholipid and about 10 to about 30 mole percent cholesterol.
The instant claims 8 and 15 recite the active agent, the phosphatidylglycerol, the phosphatidylcholine and the cholesterol in a molar ratio of 1 :2 :5: 2.5.
The instant claim 15 recites about 0.01 to about 50 mg/mL.
The combined teachings of Zhang and Greenlee, with Doyle taught 0.001 to 1000 mg/kg in a maximum of 20 mL, as previously discussed. Adler-Moore taught the antifungal compound, at least one phospholipid and cholesterol, in a mole percentage ranging from about 5-15 mole percent of the active agent, about 40-90 mole percent of the phospholipid and about 10-40 mole percent cholesterol. Kikuchi taught 10-80 mole percent phospholipid and 1-60 mol percent cholesterol.
The combined teachings of Adler-Moore and Kikuchi read on the claim limitations of the amounts of ingredients, as recited in claims 7-8.
Regarding claims 8 and 15, the combined Adler-Moore and Kikuchi read on the claimed molar ratio. For example, Adler-Moore’s teachings of 5 mole percent active and Kikuchi’s teachings of 10-80 mole percent phospholipid (phosphatidylglycerol and phosphatidylcholine) and 1-60 mole percent cholesterol, overlap the claimed ratio of 1 :2 :5 :2.5 of the active to the phosphatidylglycerol to the phosphatidylcholine to the cholesterol (5 mole active from Adler-Moore, 10 mole and 25 mole phospholipid (phosphatidylglycerol and phosphatidylcholine, respectively) from Kikuchi, and 12.5 mole cholesterol from Kikuchi.
Further regarding, claim 15, The combined teachings of Zhang and Greenlee, with Doyle taught 0.001 to 1000 mg/kg in a maximum of 20 mL, as previously discussed.
A prima facie case of obviousness exists because of overlap, as discussed above.
Nonstatutory Double Patenting
A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 13-20 and 29-30 of copending Application No. 17/432,926 in view of Kikuchi et al (US 2012/0058178 A1) and further in view of Peer et al (nature nanotechnology, 2, December 2007, 751-760).
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/954,519 in view of Kikuchi et al (US 2012/0058178 A1) and further in view of Peer et al (nature nanotechnology, 2, December 2007, 751-760).
Although the claims at issue are not identical, they are not patentably distinct from each other. The copending claims recite all of the features instantly recited for the injectable composition except for encapsulation within unilamellar vesicles.
Kikuchi taught [0072, 0169] injectable unilamellar liposomal compositions containing active compounds in the liposome internal phase (reads on an encapsulated compound) [claim 1]. The membrane constituents of the liposome comprised phospholipids (phosphatidyl choline and phosphatidyl glycerol, [0092]) and cholesterol [0095]. As an injection product, the liposome was contained within (dissolved or suspended) an aqueous solvent (distilled water) (reads on unilamellar vesicle hydrated in an aqueous phase) [0166].
Peer taught [Box 1] that nanocarriers offer many advantages over free drugs. They protect the drug from premature degradation; prevent drugs from prematurely interacting with the biological environment; enhance absorption of drugs into a selected tissue; control the pharmacokinetic and drug tissue distribution profile; and, improve intracellular penetration.
It would have been prima facie obvious to one of ordinary skill in the art to have included, within the copending claims, an encapsulating liposomal formulation comprised of phospholipid and cholesterol, and hydrated within an aqueous phase, as taught by Kikuchi [0072, 0092, 0095, 0166, 0169, claim 1]. The ordinarily skilled artisan would have been so motivated, because nanocarriers offer many advantages over free drugs, including protecting the drug from premature degradation; preventing drugs from prematurely interacting with the biological environment; enhancing absorption of drugs into a selected tissue; controlling the pharmacokinetic and drug tissue distribution profile; and, improving intracellular penetration, as taught by Peer [Box 1].
These provisional nonstatutory double patenting rejections.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELESTE A RONEY whose telephone number is (571)272-5192. The examiner can normally be reached Monday-Friday; 8 AM-6 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Frederick Krass can be reached at 571-272-0580. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CELESTE A RONEY/Primary Examiner, Art Unit 1612