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 .
Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on April 3rd, 2026 has been entered.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: “Use of Mitoxantrone Hydrochloride Liposome and Pegaspargase for the Treatment of NK/T-Cell Lymphoma”.
Status of the Claims
Claims 7-8 and 13-14 are pending in this application. Claims 1-6 and 9-12 have been cancelled by applicant.
Claim Objections
Claims 7-8 and 13-14 are objected to because of the following informalities:
Claim 7:
At the beginning of line 2, claim reads: “therapeutically effective amounts of…” Claim should read: “a therapeutically effective amount of…”
In lines 3-4, claim reads: “administration is injection form” Claim should read: “administration is in injection form”
In line 4, claim reads: “calculated on the basis of mitoxantrone…” Claim should read: “calculated on the basis of mitoxantrone content…”
In line 5, claim reads: “mitoxantrone hydrochloride liposome is 8 to 30 mg/m2, and an administration cycle of the mitoxantrone hydrochloride liposome is once every 3 weeks…” For the sake of conciseness and clarity, claim should read: “mitoxantrone hydrochloride liposome is 8 to 30 mg/m2, administered once every 3 weeks…”
Claim 8:
In line 4, claim reads: “based of mitoxantrone…” Claim should read: “calculated on the basis of mitoxantrone content…”
Claims 13-14:
Line 1 of both claims reads: “wherein a particle size…” Claims should read: “wherein the particle size…”
Lines 1-2 of both claims reads: “particle size of mitoxantrone hydrochloride liposomal is about…” Claims should read: “particle size of the mitoxantrone hydrochloride liposomes is about…”
Line 2 of both claims reads: “ and the mitoxantrone hydrochloride…” Claims should read: “and wherein the mitoxantrone hydrochloride…”
Line 3 of both claims reads: “1) the active ingredient mitoxantrone…” Claims should read: “1) mitoxantrone…”
Lines 3-4 of both claims read: “2) a lipid molecular bilayer contains phospholipid…” Claims should read: “2) a lipid molecular bilayer, which contains a phospholipid …”
Appropriate correction is required.
Duplicate Claim Warning
For the purposes of compact prosecution, Applicant is advised – IF in an effort to overcome the 112(b) rejection of claim 7, Applicant deletes the limitation: “and the administration is in injection form”, this amendment will render claims 7 and 8 as substantial duplicates of each other. In that case, Applicant is advised that should claim 7 be found allowable, claim 8 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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 7-8 and 13-14 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation “administration is in injection form”, and the claim also recites “pegaspargase…administered intramuscularly” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 13 is rejected for depending upon the limitations of claim 7.
Claim 8 reads: “a method…wherein: on the basis of administration of pegaspargase to a patient…the method further comprises administration of…” – the language of this claim is unclear. What does Applicant mean by: “on the basis of administration of pegaspargase” (?) Examiner suggests rewording this claim to read: “a method…comprising administration of a therapeutically effective amount of pegaspargase in combination with a therapeutically effective amount of mitoxantrone hydrochloride liposome…” – for the purposes of examination, this claim will be interpreted as intending the meaning conveyed by this suggested form.
Claim 14 is rejected for depending upon the limitations of claim 8.
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.
Claims 7-8 and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Neoplasma, 61, 2, 2014, 225-232 – Previously cited) (“Zhang”); in view of Yang et al. (Cancer Chemother Pharmacol, 2014, 74:637–646 – previously cited) (“Yang”).
Regarding claims 7-8 and 13-14, Zhang teaches a pegaspargase (PEG-Asp) based regimen for the treatment of newly-diagnosed extra-nodal natural killer/T-cell lymphoma (reading on treatment-naïve) (title and abstract). Zhang discloses treatment of 12 extranodal NK/T-cell Lymphoma (ENKL) newly diagnosed patients (abstract), 9 of whom had nasal ENKL presentation and 3 of whom had extra nasal presentation (page 226, col. 2, last para.). Zhang further discloses a treatment regimen comprising pegaspargase and other anticancer agents, like gemcitabine, cisplatin, and dexamethasone (table 1 and abstract) for treating nasal ENKL. Zhang specifically discloses their patients received intramuscular doses (reading on injection dosage form) of 2500 IU/m2 of PEG-Asp every 21 days (3 weeks) (Table 1, page 226).
While Zhang does not teach: (i) combination therapy with mitoxantrone liposome (Plm60) or dosage regimen of Plm60 for the treatment of NK/T-cell lymphoma (ENKL) (all instant claims); (ii) phosphatidylcholine as the bilayer phospholipid in the mitoxantrone liposome (claims 13-14); the teachings of Yang are relied upon for these disclosures.
Yang discloses Plm60-s as a pegylated liposomal mitoxantrone formulation, which is administered as an intravenous infusion at 6-18 mg/m2 every 4 weeks (abstract, methods) concluding that Plm60-s is safer than mitoxantrone, which is mainly used for the treatment of lymphoma and solid tumors (abstract – results; and Introduction, lines 1-2). Yang further teaches encapsulation of mitoxantrone (active ingredient) into pegylated liposomal small unicellular vesicles about 60 nm large, made from hydrogenated soy phosphatidylcholine (HSPC) – reading on phospholipid with Tm higher than body temperature – cholesterol, and pegylated lipid, which enhances mitoxantrone’s therapeutic activity and safety (claims 11 and 13) (page 638, col. 1, para. 2, lines 1-5).
Therefore, regarding the method of treating ENKL with a mitoxantrone liposome and pegaspargase formulation, as recited in instant claims 7-8, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer pegaspargase, as taught by Zhang, in combination with Yang’s Plm60. One of ordinary skill would have been motivated to combine these treatments with a reasonable expectation of success in view of Zhang’s disclosure that NK/T-cell lymphoma has poor prognosis with no current consensus on the optimal treatment for the disease, and their reports of the efficacy of pegaspargase-based treatment regimens (abstract and Table 6, page 230); further in view of Yang’s teachings that: (i) liposomal mitoxantrone showed improved PK properties, good tolerability, improved safety, and potential efficacy in patients with advanced lymphoma versus mitoxantrone alone, and (ii) Yang’s disclosure of Plm60 administration for treating non-Hodgkin lymphoma (Table 2, pages 641-642), in view of the fact that NK/T cell lymphoma is a type of non-Hodgkin lymphoma (page 1 of instant spec., lines 7-9).
Applicant is advised that the courts have found that “[i]t 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 re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two agents.
Further regarding claims 7-8, Zhang’s 2500 IU/m2 of PEG-Asp every 21 days (3 weeks) and Yang’s 6-18 mg/m2 every 4 weeks closely overlaps with instantly claimed ranges of PEG-Asp and Plm60. Thus, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See 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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding claims 13 and 14, Yang teaches encapsulation of mitoxantrone (active ingredient) into pegylated liposomal small unicellular vesicles about 60 nm large, made from hydrogenated soy phosphatidylcholine (HSPC), (page 638, col. 1, para. 2, lines 1-5). Thus, Yang anticipated the instant mitoxantrone hydrochloride formulation.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. 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 7-8 and 13-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,583,508 B2 (US ‘508); in view of Zhang et al. (Neoplasma, 61, 2, 2014, 225-232).
Regarding instant claims 7-8 and 13-14, US ‘508 claims a method of treating lymphoma (mentioning T cell lymphoma in US ‘508 claims 1 and 4) comprising administration of a liposomal preparation of mitoxantrone with a phospholipid with a Tm higher than body temperature, such as HSPC, and a size of about 30-80 nm (US ‘508 claims 1-3) – reading on instant all the claims.
Further regarding instant claims 7-8, US ‘508 claims administration of their mitoxantrone formulation once per 3-6 weeks at 14-24 mg/m2 (US ‘508 claim 5), administered orally or via injection (US ‘508 claim 8).
While US ‘508 does not specifically teach: (i) coadministration of pegaspargase (all claims); (ii) treatment of NK/T-cell lymphoma (all claims); (iii) treatment of treatment-naïve nasal extranodal NK/T-cell lymphoma (ENKL) (claims 3-4); (iv) co-administration of other drugs (claim 5); the teachings of Zhang are relied upon for these disclosures.
Zhang teaches a pegaspargase (PEG-Asp) based regimen for the treatment of newly-diagnosed extra-nodal natural killer/T-cell lymphoma (reading on treatment-naïve) (title). Zhang also discloses pegaspargase being administered with other anticancer agents (Table 1 and page 226, col. 2, para. 3).
Therefore, regarding the method of treating NK/T-cell lymphoma with a mitoxantrone liposome and pegaspargase formulation, as recited in instant claims 7-8, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to pegaspargase in combination with US ‘508’s mitoxantrone liposome formulation. One of ordinary skill would have been motivated to combine these treatments with a reasonable expectation of success in view of US ‘508’s teachings that their liposomal mitoxantrone was effective for treating T-cell lymphoma; further in view of Zhang’s disclosure that NK/T-cell lymphoma has poor prognosis with no current consensus on the optimal treatment for the disease, and their reports of the efficacy of pegaspargase-based treatment regimens (abstract and Table 6, page 230).
Applicant is reminded that the courts have found that “[i]t 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. It is therefore obvious to provide a mixture of the two agents.
Regarding the claimed dosages and ranges of time of administration, Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Claims 7-8 and 13-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 and 11-21 of copending Application No. 18/564,796 (Copending ‘796); in view of Zhang et al. (Neoplasma, 61, 2, 2014, 225-232).
Regarding instant claims 7-8 and 13-14, Copending ‘796 claims a method of treating advanced lymphoma or refractory/relapsed lymphoma (Copending ‘796 claims 1 and 20) comprising administration of mitoxantrone hydrochloride liposome, wherein the liposome contains a phospholipid with a Tm higher than body temperature, such as HSPC, and a size of about 30-80 nm (Copending ‘796 claim 8) – reading on instant all the claims.
Further regarding instant claims 7-8, Copending ‘796 speaks to administration of their mitoxantrone formulation once per 3-4 weeks at 8-150 mg/m2 (Copending ‘796 claims 12-13 and 16), administered orally or via injection (Copending ‘796 claim 14).
Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
While Copending ‘796 does not specifically teach: (i) coadministration of pegaspargase (all claims); or (ii) treatment of NK/T-cell lymphoma (all claims); the teachings of Zhang et al. are relied upon for these disclosures.
Zhang teaches a pegaspargase (PEG-Asp) based regimen for the treatment of newly-diagnosed extra-nodal natural killer/T-cell lymphoma (title). Zhang also discloses pegaspargase being administered with other anticancer agents (Table 1 and page 226, col. 2, para. 3).
Therefore, regarding the method of treating NK/T-cell lymphoma with a mitoxantrone liposome and pegaspargase, as recited in the interpretation of instant claims 7-8, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to pegaspargase in combination with Copending ‘796’s mitoxantrone liposome formulation. One of ordinary skill would have been motivated to combine these treatments with a reasonable expectation of success in view of Copending ‘796’s teachings that their liposomal mitoxantrone was effective for treating advanced/refractory/relapsed lymphomas; further in view of Zhang’s disclosure that NK/T-cell lymphoma has poor prognosis with no current consensus on the optimal treatment for the disease, and their reports of the efficacy of pegaspargase-based treatment regimens (abstract and Table 6, page 230).
Applicant is reminded that the courts have found that “[i]t 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. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 7-8 and 13-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 9-22 of copending Application No. 18/023,161 (Copending ‘161); in view of Zhang et al. (Neoplasma, 61, 2, 2014, 225-232).
Regarding instant claims 7-8 and 13-14, Copending ‘161 claims a method of treating treatment naïve peripheral T-cell lymphoma (PTCL) (Copending ‘161 claim 1) comprising administration of mitoxantrone liposome, wherein the liposome contains a phospholipid with a Tm higher than body temperature, such as HSPC, and a size of about 30-80 nm (Copending ‘161 claim 11) – reading on instant all the claims.
Regarding instant claims 7-8, Copending ‘161 speaks to administration of their mitoxantrone formulation once per 3-4 weeks at 8-30 mg/m2 (Copending ‘161 claim 10), administered orally or via injection (Copending ‘161 claim 15).
Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
While Copending ‘161 does not specifically teach: (i) coadministration of pegaspargase (all claims); (ii) treatment of NK/T-cell lymphoma (all claims); the teachings of Zhang et al. are relied upon for these disclosures.
Zhang teaches a pegaspargase (PEG-Asp) based regimen for the treatment of newly-diagnosed extra-nodal natural killer/T-cell lymphoma (title). Zhang also discloses pegaspargase being administered with other anticancer agents (Table 1 and page 226, col. 2, para. 3).
Therefore, regarding the method of treating NK/T-cell lymphoma with a mitoxantrone liposome and pegaspargase formulation, as recited in the interpretation of instant claims 7-8, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to pegaspargase in combination with Copending ‘161’s mitoxantrone liposome formulation. One of ordinary skill would have been motivated to combine these treatments with a reasonable expectation of success in view of Copending ‘161’s teachings that their liposomal mitoxantrone was effective for treating peripheral T-cell lymphomas; further in view of Zhang’s disclosure that NK/T-cell lymphoma has poor prognosis with no current consensus on the optimal treatment for the disease, and their reports of the efficacy of pegaspargase-based treatment regimens (abstract and Table 6, page 230).
Applicant is reminded that the courts have found that “[i]t 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. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Claim Rejections - 35 USC § 103
Applicant's arguments filed 04/03/2026 have been fully considered but they are not persuasive.
Applicant has compared the efficacy of their combination therapy, comprising pegaspargase, with other reported therapies for the treatment of NKTCL reported in the literature. These references were never cited in an IDS or properly entered into the record, as such, they are being cited in the 892-form included with this action. Specifically, Applicant cites:
Wang et al. (JAMA, 2022, 8, 1035-1041) (“Literature 1”) – it is noted that Applicant has made a mistake in filling out the table provided, as the ORR for the DDGP treatment regimen was 90%, not 0% - Examiner corrected this typo in the table below;
(ii) Hu et al. (Frontiers in Oncology, 2022, 12, Article 839252, 7 pages) (“Literature 2”) - it is noted that Applicant made a mistake in the table – ORR was 87.3%, not 3%, and CR was 75.9%, not 9% - Examiner corrected these issues below; and
(iii) Liu et al. (Frontiers in Oncology, 2021, 10, Article 583050, 6 pages) (“Literature 3”) – Once again, Applicant entered the wrong values in the Table…ORR should be 65.2% vs 47.8% for asparaginase-containing and asparaginase-free regimens, respectively; and CR should be 45.5% vs 23.9% for asparaginase-containing and asparaginase-free regimens, respectively. Literature 3 also discloses a pegaspargase regimen resulted in 95% ORR and 71% CR – Applicant didn’t report these numbers; however, Examiner has included them below.
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Literature 3
DDGP regimen (see page 5, col. 1, para. 2, lines 13-15)
95%
71%
Table 1 from the instant specification is reproduced below for convenience. This table discloses the results of administration of the instant therapeutic regimen comprising pegaspargase with mitoxantrone hydrochloride liposome. This treatment, as seen below, results in 100% ORR and 81.8% CR for treatment-naïve subjects, and 77.8% ORR and 33.3% CR for relapsed/refractory subjects. These results are comparable with Zhang’s disclosure, who discloses a 100% ORR and 83.3% CR after a pegaspargase treatment regimen in newly diagnosed subjects. With respect to Literature 1, (Wang et al.) they disclose 90% ORR and 67.5% CR for their DDGP group (pegaspargase treatment) (see Table 2, page 10) in treatment-naïve subjects. Literature 2, (Hu et al.) discloses 87.3% ORR and 75.9% CR in their treatment-naïve subjects who received a pegaspargase regiment. It is noted that Literature 3 (Liu et al.) does not administer pegaspargase, but rather asparaginase – it is known in the art that pegaspargase (pegylated asparaginase) is more effective than asparaginase alone, therefore, the results Applicant cites from literature 3 are not commensurate with the scope of the claims and have not been considered – instead, from Literature 3, Examiner has considered the more relevant results disclosed for a pegaspargase treatment – see the table above. Similarly, none of the literature references cited show results for refractory/relapsed subjects, and therefore, the data is not commensurate in scope with the claims in that respect.
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Applicant states the following (see pages 5-6 of remarks filed 04/03/2026):
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Applicant states the technical solution of the instant application produced “unexpected excellent efficacy”. Applicant purports that the instant combination of mitoxantrone HCl liposome results in “significantly better results in ORR and CR1 than prior art technologies2 which cannot reasonably be expected based on the teachings of Zhang and Yang”. Applicant states the efficacy achieved by instant treatment is superior to the teachings of Zhang and Yang.
This is not persuasive. As shown in all the results discussed above, the ORR and CR obtained with the instant pegaspargase therapy is comparable, if not inferior (see CR values), to Zhang’s pegaspargase therapy. Furthermore, the instant ORR and CR values reported are not “unforeseen” in comparison with the pegaspargase regiments disclosed by Literatures 1, 2, and 3, as only small improvements of 5-10% are observed among the instant relatively small sample sizes. In addition, Literature 3, cited by Applicant, states that “limited sample size might influence treatment response rates and survival outcome” (see page 5, col. 1, para. 2, lines 13-17), which would explain the higher ORRs in the instant studies and Zhang’s ORRs (both of which had small samples sizes of 11 and 12 patients, respectively, while Literatures 1 and 2 had larger sample sizes of 40 and 80 patients, respectively – which would be expected to afford more accurate data, as can be seen from the varying numbers for the same pegaspargase treatment regimen DDGP of Zhang vs Literature 1 (N = 12 vs 40). While Applicant asserts there is synergism in their combination therapy, the data provided does not corroborate this statement. It would be helpful, in order to prove the presence of synergy and overcome the obviousness rejections presented herein, if Applicant could demonstrate ORR and CR of individual components in the instantly claimed treatment regimen, compared to the combination thereof.
Double Patenting
Applicant requests postponing response to NSDP rejections of record until claims are allowable. This is not persuasive. Rejections are maintained.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
1 While Applicant states “DCR” and not CR, Examiner believes they intended CR, as this is the comparative data that was provided – no DCR comparative data was provided.
2 Applicant is advised that Literatures 1, 2, and 3 provided do not constitute prior art based on their publication date and the effective filing date of 08/07/2020 of the instant application.
Prosecution Insights