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 .
Status
Applicant’s response dated 29 April 2026 to the previous Office action dated 12 February 2026 is acknowledged. Pursuant to amendments therein, claims 34-40, 43, and 45-53 are pending in the application.
The rejection under 35 U.S.C. 112 regarding a relative term made in the previous Office action is maintained herein as set forth below.
The rejection under 35 U.S.C. 112 regarding insufficient antecedent basis made in the previous Office action is withdrawn in view of applicant’s claim amendments.
The rejection under 35 U.S.C. 102 made in the previous Office action is withdrawn in view of applicant’s claim amendments.
The rejections under 35 U.S.C. 103 made in the previous Office action are withdrawn in view of applicant’s claim amendments, but new rejections under 35 U.S.C. 103 are made herein in view of applicant’s claim amendments.
The double patenting rejections made in the previous Office action are withdrawn in view of applicant’s claim amendments.
Response to Arguments
Applicant's arguments filed 29 April 2026 regarding the relative term indefiniteness rejection made in the previous Office action have been fully considered but they are not persuasive. Applicant argues that Li et al. (of record) defines“poorly soluble” in paragraphs [0011] and [0038] (remarks pages 5-6). In response, Li et al. does not define the term “poorly soluble” in such paragraphs or in any other paragraphs.
Applicant’s arguments, see remarks, filed 29 April 2026, with respect to the rejection(s) under 35 U.S.C. 102 and 103 made in the previous Office action have been fully considered and are persuasive. Therefore, the rejections have been withdrawn. However, upon further consideration, a new ground(s) of rejection under 35 U.S.C. 103 is/are made as set forth below.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 36-40 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “poorly soluble” in claims 36 and 40 is a relative term which renders the claim indefinite. The term “poorly soluble” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear to what extent the precipitate must be soluble to be poorly soluble, rendering the claim indefinite. Claims 37-39 are rejected as depending upon claim 36 without remedying such deficiency.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 34-39, 43, and 45-53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ahmad et al. (US 2003/0219476 A1; published 27 November 2003; of record) in view of Nicoletto et al. (Cancer Chemotherapy and Pharmacology, 2000, Vol. 45, pages 457-462).
Regarding claim 34, Ahmad et al. discloses a method of treating a mammalian disease comprising: administering to a mammal a pharmaceutical composition comprising a therapeutically effective amount of mitoxantrone in a liposomal formulation (claim 1) wherein the mammal is human (claim 2) wherein disease in particular is ovarian cancer (paragraph [0031]) wherein the mitoxantrone is mitoxantrone hydrochloride (paragraph [0002]; Example 6), which reads on the claimed method of treating ovarian cancer, gastric cancer, or head and neck squamous carcinoma in a subject, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of mitoxantrone hydrochloride liposome.
Further regarding claim 34, Ahmad et al. does not disclose that the ovarian cancer is platinum-refractory or platinum-resistant recurrent ovarian cancer as claimed. However, Nicoletto et al. discloses treatment of ovarian cancer with mitoxantrone (title) wherein patients are previously treated with platinum compounds yet had residual disease (Results page 458; Table 1 page 459).
Further regarding claim 34, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ahmad et al. and Nicoletto et al. by practicing the method of Ahmad et al. as discussed above wherein the ovarian cancer therein is in patients previously treated with platinum compounds yet having residual disease (i.e., the ovarian cancer is platinum-refractory or platinum-resistant recurrent ovarian cancer as claimed) as suggested by Nicoletto et al., with a reasonable expectation of success. A person of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so to treat a type of ovarian cancer known to be treated with mitoxantrone as suggested by Nicoletto et al. given that Ahmad et al. teaches treatment of ovarian cancer with mitoxantrone.
Regarding claim 35, claim 1 of Ahmad et al. lists no other active ingredient (claim 1), which reads on the claimed mitoxantrone hydrochloride liposome being the only active ingredient in the pharmaceutical composition.
Regarding claim 36 (as it refers to claim 34), Ahmad et al. discloses a method of treating a mammalian disease comprising: administering to a mammal a pharmaceutical composition comprising a therapeutically effective amount of mitoxantrone in a liposomal formulation (claim 1) wherein the mammal is human (claim 2) wherein disease in particular is ovarian cancer (paragraph [0031]) wherein the mitoxantrone is mitoxantrone hydrochloride (paragraph [0002]; Example 6), which reads on the claimed method of treating ovarian cancer, gastric cancer, or head and neck squamous carcinoma in a subject, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of mitoxantrone hydrochloride liposome.
Further regarding claim 36, Ahmad et al. discloses that the liposome vesicles have a size of about 0.1 µm or less (i.e., about 100 nm or less), which overlaps the claimed range of about 30-80 nm, and a prima facie case of obviousness exists where prior art and claimed ranges overlap per MPEP 2144.05(I).
Regarding claim 37, Ahmad et al. discloses that the liposome vesicles have a size of about 0.1 µm or less (i.e., about 100 nm or less), which overlaps the claimed range of about 40-60 nm, and a prima facie case of obviousness exists where prior art and claimed ranges overlap per MPEP 2144.05(I).
Regarding claim 38, the claimed recitation of the multivalent counter ion being sulfate, citrate, or phosphate merely further limits the multivalent counter ion recited in claim 36, but such multivalent counter ion remains optional and is not required per claims 36 and 38.
Regarding claim 39, the claimed recitation of the phospholipid being a listed species merely further limits the phospholipid recited in claim 36, but such phospholipid remains optional and is not required per claims 36 and 39.
Regarding claim 43, the claimed recitation of the head and neck squamous cell carcinoma being a listed type merely further limits the head and neck squamous cell carcinoma recited in claim 34, but such head and neck squamous cell carcinoma remains optional and is not required per claims 34 and 43.
Regarding claim 45, the claimed recitation of the first line therapy being a listed type merely further limits the first line therapy recited in claim 34, but such first line therapy remains optional and is not required per claims 34 and 45.
Regarding claim 46, Ahmad et al. discloses that the composition is injected (Examples 8-12, 14, 16, 18), which reads on the claimed pharmaceutical composition being in the form of an injection.
Regarding claim 47, Ahmad et al. discloses that the composition is a solution (paragraph [0028]; Examples 6-7) and is injected (Examples 8-12, 14, 16, 18), which reads on the claimed pharmaceutical composition being in the form of a liquid injection.
Regarding claim 48, Ahmad et al. discloses that the composition is a solution (paragraph [0028]; Examples 6-7) and is injected (Examples 8-12, 14, 16, 18) and has a 1 mg/mL mitoxantrone concentration (Example 7), which reads on the claimed pharmaceutical composition being in the form of a liquid injection with 0.5-5 mg/mL mitoxantrone.
Regarding claim 49, Ahmad et al. discloses that the composition is a solution (paragraph [0028]; Examples 6-7) and is injected (Examples 8-12, 14, 16, 18) and has a 1 mg/mL mitoxantrone concentration (Example 7), which reads on the claimed pharmaceutical composition being in the form of a liquid injection with 1-2 mg/mL mitoxantrone.
Regarding claim 50, Ahmad et al. discloses that intravenous administration is preferred (paragraph [0032]) and injections were via i.v. (Examples 8-14 and 16-19), which reads on the claimed administration by intravenous administration.
Regarding claim 51, Ahmad et al. discloses that intravenous administration is preferred (paragraph [0032]) and injections were via i.v. (Examples 8-14 and 16-19), and the dosage form is dispensed by infusion over 45 minutes (paragraph [0024]), which reads on the claimed infusion intravenous administration time of 30-120 minutes.
Regarding claim 52, Ahmad et al. discloses that patients are treated with i.v. administration of liposomal mitoxantrone every three weeks (Example 19), which reads on the claimed administration once every four weeks or three weeks.
Regarding claim 53, Ahmad et al. discloses that liposomal mitoxantrone is administered at dose 9-30 mg/m2 (paragraph [0109] Table 7), which reads on the claimed therapeutically effective amount of 8-30 mg/m2.
Claim(s) 34-40, 43, 45-47, and 50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US 2011/0002977 A1; published 06 January 2011; of record) in view of Xu et al. (CN 112043832 A; published 08 December 2020; citations herein to English machine translation made 17 June 2026).
Regarding claim 34, Li et al. discloses a method for the treatment of a tumor in a patient, which method comprises: administering a liposomal pharmaceutical preparation to a patient in need of the treatment; wherein (1) the liposomal drug comprises a multivalent ionic drug as active ingredient (claim 38) wherein cancers include gastric carcinoma and the drug is preferably mitoxantrone (paragraph [0034]) wherein doses of 2-8 mg/kg of mitoxantrone are used (Table 7) wherein mitoxantrone hydrochloride is used (Example 1).
Further regarding claim 34, although Li et al. does not disclose a single embodiment including all claimed elements as discussed above, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to follow the suggestions of Li et al. as discussed above and to treat gastric cancer in a patient in need thereof by administering to the patient a liposomal pharmaceutical preparation comprising mitoxantrone hydrochloride in liposomes in a dosage of 2-8 mg/kg (i.e., a therapeutically effective amount) per the methods and compositions as suggested by Li et al., with a reasonable expectation of success.
Further regarding claim 34, Li et al. does not disclose that the gastric cancer is advanced gastric cancer as claimed. However, Xu et al. discloses treatment of gastric cancer (title; abstract; claim 1) wherein the gastric cancer is advanced (claim 3) wherein a chemotherapeutic agent used in such treatment is mitoxantrone (claim 4).
Further regarding claim 34, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Li et al. and Xu et al. by practicing the method of Li et al. as discussed above wherein the gastric cancer therein is advanced gastric cancer as suggested by Xu et al., with a reasonable expectation of success. A person of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so to treat a type of gastric cancer known to be treated with mitoxantrone as suggested by Xu et al. given that Li et al. teaches treatment of gastric cancer with mitoxantrone.
Regarding claim 35, claim 38 of Li et al. lists no other active ingredient (claim 38), which reads on the claimed mitoxantrone hydrochloride liposome being the only active ingredient in the pharmaceutical composition.
Regarding claim 36, Li et al. discloses the liposome of the liposomal drug has a size of 30-80 nm (claim 38), which reads on the claimed liposome having a particle size of about 30 to 80 nm.
Regarding claim 37, Li et al. discloses the liposome of the liposomal drug has a size of 30-80 nm (claim 38), which overlaps the claimed liposome having a particle size of about 40 to 60 nm, and a prima facie case of obviousness exists where prior art and claimed ranges overlap per MPEP 2144.05(I).
Regarding claim 38, the claimed recitation of the multivalent counter ion being sulfate, citrate, or phosphate merely further limits the multivalent counter ion recited in claim 36, but such multivalent counter ion remains optional and is not required per claims 36 and 38.
Regarding claim 39, the claimed recitation of the phospholipid being a listed species merely further limits the phospholipid recited in claim 36, but such phospholipid remains optional and is not required per claims 36 and 39.
Regarding claim 40, Li et al. discloses forming the liposome using hydrogenated soybean phosphatidylcholine, cholesterol and PEG2000-modified distearoyl phosphatidyl ethanolamine in a weight ratio of 3:1:1 (Example 2; claim 33), which reads on the claimed phospholipid bilayer in the mitoxantrone hydrochloride liposome contains hydrogenated soy phosphatidylcholine, cholesterol and PEG2000 modified distearoylphosphatidylethanolamine in a mass ratio of about 3:1:1; and Li et al. discloses that the liposome comprises a multivalent counter ion, which reads on the claimed mitoxantrone hydrochloride interacting with a multivalent acid ion in the liposome to form a poorly soluble precipitate; and Li et al. discloses that the liposome of the liposomal drug has a size of 30-80 nm (claim 38), which overlaps the claimed liposome having a particle size of about 60 nm, and a prima facie case of obviousness exists where prior art and claimed ranges overlap per MPEP 2144.05(I). Although Li et al. does not explicitly disclose the formation of a poorly soluble precipitate due to the interaction with the multivalent ion in the liposome, since the composition of Li et al. is substantially identical to the composition in the claimed method, it is presumed that such property/formation is inherent in the composition of Li et al. per MPEP 2112(V) and 2112.01(I), and thus the method of Li et al. in view of Xu et al., given that compositions that are physically the same must have the same properties per MPEP 2112.01(II).
Regarding claim 43, the claimed recitation of the head and neck squamous cell carcinoma being a listed type merely further limits the head and neck squamous cell carcinoma recited in claim 34, but such head and neck squamous cell carcinoma remains optional and is not required per claims 34 and 43.
Regarding claim 45, the claimed recitation of the first line therapy being a listed type merely further limits the first line therapy recited in claim 44, but such first line therapy remains optional and is not required per claims 34 and 44-45.
Regarding claim 46, Li et al. discloses that the composition is injected (paragraph [0045]; Examples 12-14 and 18-19), which reads on the claimed pharmaceutical composition being in the form of an injection.
Regarding claim 47, Li et al. discloses that the composition is a solution (Examples 1-3) and is injected (paragraph [0045]; Examples 12-14 and 18-19), which reads on the claimed pharmaceutical composition being in the form of a liquid injection.
Regarding claim 50, Li et al. discloses that injections were intravenous (Examples 18, 20), which reads on the claimed administration by intravenous administration.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL B. PALLAY whose telephone number is (571)270-3473. The examiner can normally be reached Monday through Friday from 8:30 AM to 5:00 PM Eastern Time.
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, Sue Liu can be reached at (571)272-5539. 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.
/MICHAEL B. PALLAY/Primary Examiner, Art Unit 1617
Prosecution Insights