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 .
DETAILED ACTION
The amendment to the claims filed after non-final office action on May 19, 2026 is acknowledged. Claims 1-66 were canceled, claims 67-69 were amended and claims 67-76 are pending in the instant application.
The was restriction deemed proper and made FINAL in the previous office action. Claims 67-76 are examined on the merits of this office action.
Withdrawn Rejections/Objections
The objection to claim 67 is hereby withdrawn in view of amendment of the claims filed May 19, 2026.
The rejection of claims 67-76 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of amendment of the claims filed May 19, 2026.
Maintained/Revised Rejections
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.
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.
Claim(s) 67-76 remain rejected under 35 U.S.C. 103 as being unpatentable over Elliott (WO2017011312 A1, cited previously) in view of Zang (Journal of Controlled Release 303 (June, 2019) 109–116, cited previously) as evidenced by Buduhan (Symptom Management Guidelines: Chemotherapy – Induced Peripheral Neuropathy (CIPN), published 2010, pages 1-8).*All references cited previously.
Elliott teaches a composition comprising a peptide amphiphile lipid micelle (PALM) comprising a peptide of X1-X20 (See claim 1, which is identical to the peptide of the instant claims, also see claim 10) and treating cancer. Regarding claim 67, Elliott teaches wherein the PALM comprises a lipid component of sphingomyelin and or more additional phospholipids (see claim 10). Elliott teaches a cargo molecule comprising A-R-L-X(formula I) wherein A is an agent having a hydroxyl or an amine group; R is a hydroxyl or an amine group of the agent; L is a linker; and X is an anchor moiety selected from the group consisting of cholesterol, a-tocotrienol, β-tocotrienol, γ-tocotrienol, and δ-tocotrienol (see claim 27 of Elliott). Regarding claims 67 and 75, Elliott teaches wherein the peptide in the PALM consists of instant SEQ ID NO:35 (see Claim 39 of Elliott) and intravenous administration (see paragraph 00125). Elliott teaches administering PALM containing chemotherapeutics with lipid and the cargo for treating cancer (see paragraph 00164 for example, Figure 8).
Regarding claims 67 and 71, Elliott teaches wherein the phospholipid is phosphatidylcholine (see claim 12) and in particular POPC (see claim 14).
Regarding claim 67, Elliott teaches administering to patients with chemotherapeutics including paclitaxel (see 36). Regarding claims 67, 72, Elliott teaches a paclitaxel conjugates encompassed by instant claims (see paragraphs 0035-0036, paclitaxel 2’-cholesteryl carbonate and paclitaxel 2’-5-tocotrienyl carbonate and also paclitaxel delta-tocotrienyl carbonate in paragraph 0133, Example 8).
Elliott teaches “wherein at least one cargo molecule is a compound conjugate having the formula (I):A-R-L-X (formula I) wherein A is an agent having a hydroxyl or an amine group; R is a hydroxyl or an amine group of the agent; L is a linker; and X is an anchor moiety selected from the group consisting of cholesterol, a-tocotrienol, β-tocotrienol, γ-tocotrienol, and δ-tocotrienol” (see claim 27). Elliott further teaches “wherein R is a hydroxy group and the anchor moiety is covalently bonded to agent by a carbonate ester bond” (see claim 28). Elliott teaches where the anchor moiety is δ -tocotrienol (see claim 31). Elliott teaches PALM Containing delta-tocotrienyl carbamate ester of paclitaxel (see paragraph 00110).
Regarding claim 76, Elliott teaches wherein the cancer type is ovarian cancer (see Example 18, Ovarian cancer cells treated with PALM containing paclitaxel cholesteryl carbonate).
Regarding claims 67, 73-74, Elliott teaches wherein the PALM lyophilizate is reconstituted (in water, aqueous) and then sterilized (see paragraph 00121).
Elliott does not teach identifying a patient having CIPN associated with paclitaxel treatment or administering the formulation specifically to reduce paclitaxel induced CIPN.
However, Zang teaches “Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior efficacy and safety profiles for other drugs” (see abstract). Zang teaches that paclitaxel has been discontinued in cancer treatments due to grade 2-3 peripheral neuropathy (see Discussion, paragraph 3). Zang teaches “liposomes containing paclitaxel were successfully developed and demonstrated reduced neurotoxicity in-vitro in neuronal cells and prevented development of peripheral neuropathy in-vivo. This proof of concept study showed that formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs” (see Abstract, conclusion).
It would have been obvious before the effective filing date of claimed invention to administer the peptide amphiphile lipid micelle (PALM) comprising paclitaxel of Elliott to patients with CIPN and CIPN associated with paclitaxel (neurotoxic chemotherapy) in view of Zang. One of ordinary skill in the art would have been motivated to administer Elliott’s peptide amphiphile micellar paclitaxel formulation to patients with, or at risk of paclitaxel induced CPN because Zang provides a clear rationale that encapsulating in nanoparticle systems reduces its neurotoxicity while maintaining anticancer efficacy. Elliott’s PALM system already embodies such a nanoparticle platform and teaches the same therapeutic agent. One of ordinary skill in in the art would have had a reasonable expectation of success in achieving the desired outcome-reduction in CIPN-because both references demonstrate that paclitaxel retains antitumor activity when delivered in micellar or liposomal carriers and that nanoparticle encapsulation attenuates does limiting neurotoxicity. Therefore, it would have been obvious to combine the composition of Elliott with the therapeutic context taught by Zang to arrive at the claimed method with a reasonable expectation that the resulting treatment would reduce paclitaxel inducing peripheral neuropathy while treating cancer.
Regarding “identifying a patient having CIPN associated with treatment for cancer”, Elliott in view of Zang render obvious this step. Elliot teaches paclitaxel nanoparticle (PALM) treatment for cancer, and Zang teaches that CIPN is a known adverse effect of paclitaxel and that nanoparticle paclitaxel formulations are used to reduce such neuropathy. A person of ordinary skill in the art would have been motivated to identify patients experiencing paclitaxel associated CIPN in order to administer the known nanoparticle formulation intended to reduce toxicity, which is the predictable clinical application of the combined teachings (see MPEP 2143).
Regarding the limitation of “wherein said method further reduces the pain associated with CIPN” found in instant claims 67 and 70, and “wherein said treatment reduces CIPN in said patient as compared to treatment with paclitaxel in the absence of said aqueous suspension”, Elliott in view of Zang teach the same method of the instant claims including administering the same formulation to the same patient population (cancer patients with CIPN) and thus, the effects will inherently be achieved as a result of practicing the method of Elliott in view of Zang.
Regarding the limitation of claim 67 that the amphiphilic peptide binds to the SR-B1 receptor on tumor cells, Elliott in view of Zang teaches the same amphiphilic peptide sequences recited in the instant claims for use in PALM nanoparticles. Where the prior art teaches the identical peptide sequences, receptor binding including SR-B1 is an inherent property of those peptides. Therefore, this limitation does not patentably distinguish the claim because the composition of Elliott would inherently satisfy this binding property.
Claims 68-69 further limit the method to patients having specified CIPN severity grades. Zang teaches paclitaxel induced CIPN and its clinical evaluation and severity assessment. CIPN severity grading is a well-established and routinely used clinical framework with a finite number of recognized categories (see Buduhan) used to guide treatment decisions. Once the problem of paclitaxel induced CIPN and the solution of nanoparticle paclitaxel delivery are taught, it would have been obvious before the effective filing date of the claimed invention to select a treatment threshold based on severity grade, including treating patients beginning at grade 1 or limiting treatment to more severe grades 3-4, as these represent identified and predictable options within the established grading system. This constitutes choosing from a finite number of predictable solutions with a reasonable expectation of success (the prior art combination teaches CIPN (including grade 2-3) is caused by paclitaxel and encapsulated liposomal paclitaxel reducing or prevented CIPN) and therefore is obvious to try under KSR and MPEP2143 (E). Furthermore, such selection represents routine optimization of a result effective clinical variable as described in MPEP 2144.
Response to Applicant’s Arguments
Applicant argues “First, the combination of Elliott and Zang does not teach or suggest reducing CIPN in a patient that has CIPN, as claimed. The amendments discussed above with respect to claims 67 - 69 make more clear that the patient being treated with the claimed formulation already has CIPN before the treatment and the treatment reduces already-existing CIPN. As noted in the rejection, Elliott does not teach this feature, and Applicant respectfully submits that the rejection's reliance on Zang for this feature is misplaced. Zang does not teach or suggest reducing CIPN in a patient that already has CIPN. Rather, Zang is focused on preventing or reducing CIPN at the outset using a liposomal formulation of paclitaxel. See, e.g., Zang at 114 ("In this study, the liposomal formulation of paclitaxel was less toxic to neuronal cells than paclitaxel solution and prevented development of neurotoxicity in-vivo as compared to Taxol® administration...' see also Abstract, Conclusion. Zang's study methods as described at pp. 110 - 111 did not include selecting rats with CIPN. Indeed, Zang even notes that there are limited options for treating CIPN as shown in the below excerpt from p. 114, indicating that Zang does not contemplate reducing already-present CIPN as recited in the present claims: Treatment of CIPN is mostly symptomatic (using anticonvulsants, ga- bapentin, opioids [7]) and remains largely ineffective [6]. Some prevention treatments using vitamin E, amifostine, and glutathione were reported [7]; however, discontinuation of chemotherapy or dose re- duction remains the only clinical solution [7]. Therefore, there is an urgent need to develop approaches for prevention of CIPN.
Second, to the extent the Examiner would consider Zang as reading on reducing CIPN in a patient that has CIPN, such a reading of this term necessarily applies an improper construction of this term that goes beyond the broadest reasonable interpretation. Specifically, it effectively reads out the claim language "that has CIPN" - equating "reducing CIPN in a patient that has CIPN" with "reducing CIPN in a patient." Third, the rejection further asserts that one of ordinary still in the art would have been motivated to provide the PALM composition as taught by Elliott to patients "with, or at risk of paclitaxel induced CIPN" because "Zang provides clear rationale that encapsulating [paclitaxel] in nanoparticle systems reduces its neurotoxicity while maintaining its anticancer efficacy." February 19, 2026 Office Action at p. 6. However, there are several problems with this conclusion. First, as noted above, the claims recite providing the claimed composition to patients with CIPN, not patients at risk of CIPN. As admitted in the rejection, Elliott does not teach identifying patients with CIPN or administering them any formulations to reduce existing CIPN. Likewise, as discussed, above, Zang does not disclose this feature either, since Zang only contemplates preventing or reducing CIPN at the outset, not treating or reducing CIPN after it develops. Second and relatedly, one of skill in the art would not have expected that combining Elliott and Zang as suggested in the rejection would accomplish reducing CIPN in a patient that already has CIPN, as claimed. Neither Elliott nor Zang teach or suggest such an outcome; at best, Zang only teaches that certain formulations can reduce or prevent the onset of CIPN.
Finally, Applicant submits that the liposomes of Zang are SO different from nanoparticles recited in the claims and taught by Elliott that one of skill in the art would have no basis to reasonably predict equivalence between Zang's liposomes and Elliott's liposomal nanoparticles. The rejection does not provide any rationale for why one of skill in the art would have ignored these differences, or expected to be successful despite them. Specifically, the differences between Zang's liposomes and Elliott's liposomal nanoparticles include at least the following: the liposomes of Zang's are PEGylated whereas the claimed nanoparticles do not contain PEG; the claimed nanoparticles contain an alpha helix amphiphilic peptide that is part of the micellular liposomes whereas Zang does not include any peptides in his liposomes; Zang's liposomes contain paclitaxel whereas paclitaxel in the claimed nanoparticles is part of a conjugate having a lipid selected from a specified group of claimed lipids each of which is covalently bound to paclitaxel through a carbonate bond; and Zang recites that his liposomes containing paclitaxel have a mean diameter of either 50 to 60 nm or a size of 140 ± 13 nm. In contrast thereto, Elliott describes the nanoparticles as having a mean diameter of liposomes recite an average diameter of 5 to 15 nm.² Simply comparing these two formulations and the differences therebetween, the skilled artisan would conclude that the liposomes taught in the Zang reference are unrelated to those taught by Elliott. For example, Elliott provides for paclitaxel that is covalently bound to a lipid by a carbonate bond whereas Zang uses unbound paclitaxel. Moreover, Figure 3 of Elliott shows that the nanoparticles containing a paclitaxel-carbonate-cholesterol conjugate have a diameter of about 10.2 nm whereas Zang's liposomes are at 4.9 times larger. Such a size differential does not provide the skilled artisan that Zang's teachings are applicable to and should be combined with the teachings of Elliott. In addition, Elliott teaches a peptide amphiphile lipid micelle, which has hydrophobic and hydrophilic regions; Zang's liposomes are not amphiphilic and, as such, the skilled artisan could not reasonably predict the impact of such peptides on the functionality of the liposomes.
Applicant’s arguments have been fully considered but not found persuasive. Applicant argues that the claims require treatment of a patient who already has CIPN prior to administration of the claimed composition, whereas Zang allegedly teaches only prevention of neuropathy onset. Applicant further argue that Zang’s animal studies did not involve animals preselected as already having CIPN and therefore Zang allegedly fails to teach reduction of already existing CIPN. Applicants argument is not persuasive because it improperly narrows the claim language and fails to give the claims their broadest reasonable interpretation consistent with the specification. The claims recite “reducing CIPN in a patient that has CIPN”. The claims do not recite reversal of chronic neuropathy, curing established nerve degeneration, administration only after fully developed neuropathy is diagnosed or treatment exclusively after stopping chemotherapy. Under the broadest reasonable interpretation, a patient undergoing paclitaxel therapy while experiencing neuropathic manifestations associated with CIPN reasonably constitutes a patient that has CIPN.
Zang expressly teaches reduction of neuropathic manifestations associated with paclitaxel-induced peripheral neuropathy, including reduced mechanical hypersensitivity, reduced thermal hypersensitivity, reduced neurotoxicity, reduced peripheral neuropathy manifestations, reduced nervous-system exposure to paclitaxel. For example, Zang teaches “Administration of L-PTX did not result in increased sensitivity to mechanical stimulation,” and further teaches“Taxol® treatment produced a significant reduction in reaction time to heat stimulation compared to the L-PTX treatment group” (see Results section 3). Zang additionally states “Administration of L-PTX led to a significantly lower drug exposure in the brain, spinal cord, muscle and skin compared to Taxol® treated group, which corresponds to the results of mechanical and thermal sensitivity testing” (see Section 4, Conclusion). Further, Zang expressly concludes “formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs” (see Conclusion). Thus, Zang is not limited solely to prophylaxis before any neuropathic manifestations occur, but broadly teaches reduction of neuropathic symptoms and neurotoxicity associated with paclitaxel administration. Accordingly, one of ordinary skill in the art would have reasonably understood Zang to teach or suggest reducing CIPN manifestations in patients experiencing CIPN symptoms during paclitaxel treatment.
Applicant further argues that the rejection allegedly reads out the claim limitation “that has CIPN”. Applicant argues that the rejection improperly equates “reducing CIPN in a patient” with “reducing CIPN in a patient that has CIPN.” Applicant asserts that such interpretation exceeds the broadest reasonable interpretation. Applicant’s argument is not persuasive. The rejection does not read out the limitation “that has CIPN.” Rather, the rejection interprets the claims under the broadest reasonable interpretation standard consistent with the specification. See MPEP § 2111. As discussed above, Zang teaches administration of paclitaxel nanoparticle formulations in subjects experiencing neuropathic manifestations associated with paclitaxel-induced peripheral neuropathy, including mechanical and thermal hypersensitivity. A subject exhibiting such neuropathic manifestations reasonably constitutes a subject “that has CIPN.” The claims do not require complete establishment of irreversible neuropathy prior to treatment, chronic neuropathy, or reversal of preexisting nerve degeneration. Applicant argues that Zang only teaches prevention of neuropathy development and therefore allegedly cannot support the claimed reduction of CIPN in a patient already having CIPN. Applicant’s argument is not persuasive because it selectively focuses on portions of Zang discussing prevention while disregarding Zang’s broader teachings concerning reduction of neurotoxicity and neuropathic manifestations. Although Zang discusses prevention of neuropathy onset, Zang also repeatedly teaches reducing neurotoxicity, reducing peripheral neuropathy manifestations, reducing mechanical hypersensitivity, reducing thermal hypersensitivity, reducing nervous-system exposure to paclitaxel. Notably, Zang expressly states “formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs.” The express use of the disjunctive phrase “reducing (or preventing)” indicates that Zang contemplates both reduction and prevention of neurotoxicity. Moreover, Zang correlates reduced nervous-system exposure to paclitaxel with reduced neuropathic sensitivity testing outcomes. Accordingly, one of ordinary skill in the art would reasonably expect that nanoparticle paclitaxel formulations reducing nervous-system exposure would reduce CIPN manifestations in patients experiencing neuropathic symptoms. Applicant argues that one of ordinary skill in the art would not have reasonably expected combining Elliott and Zang to reduce CIPN in patients already having CIPN. Applicant’s argument is not persuasive because Zang provides explicit mechanistic rationale supporting reasonable expectation of success (see above teachings of Zang). Specifically, Zang teaches “Administration of L-PTX led to a significantly lower drug exposure in the brain, spinal cord, muscle and skin compared to Taxol® treated group, which corresponds to the results of mechanical and thermal sensitivity testing.” A person of ordinary skill in the art would therefore have reasonably expected that alternative nanoparticle paclitaxel systems, including those taught by Elliott, would likewise reduce neurotoxicity/CIPN manifestations through analogous biodistribution effects. Absolute predictability is not required. See MPEP § 2143.02(VI); In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988).
Applicant argues that Zang uses PEGylated liposomes, Elliott uses peptide amphiphile nanoparticles, paclitaxel conjugation differs, particle sizes differ, and therefore the systems allegedly are unrelated. Applicant’s argument is not persuasive because nonidentity between references does not preclude obviousness. Rather, Zang is relied upon for teaching of nanoparticle/liposomal paclitaxel formulations reducing neurotoxicity, reduced nervous-system exposure, reduced neuropathic manifestations associated with paclitaxel administration, and the relationship between nanoparticle formulation properties and neurotoxicity reduction. The differences in PEGylation, particle size, peptide inclusion and conjugation chemistry represent formulation variables routinely optimized in the nanoparticle drug-delivery art. Indeed, Zang itself recognizes optimization of nanoparticle properties, stating “Future studies are needed to determine the optimal size of particulates for preserving (or enhancing) efficacy and minimizing neurotoxicity.” Further, obviousness does not require physical substitution of one reference into another, nor does it require that the references be identical. See MPEP § 2143.
Applicant argues that Zang’s studies did not involve selecting rats already exhibiting CIPN prior to treatment. Applicant’s argument is not persuasive. The rejection relies on Zang’s teachings regarding reduction of neuropathic manifestations and reduced neurotoxicity associated with nanoparticle paclitaxel formulations, not on any requirement that the precise experimental protocol identically match the claimed method. Rather, the relevant inquiry is whether the combined teachings of the references would have suggested the claimed invention to one of ordinary skill in the art with a reasonable expectation of success. As discussed above, Zang expressly teaches reduction of neuropathic manifestations associated with paclitaxel neurotoxicity and provides mechanistic rationale linking reduced nervous-system exposure with reduced neuropathy-related sensitivity. Accordingly, the combined teachings of Elliott and Zang would have reasonably suggested the claimed method.
The Examiner maintains that “It would have been obvious before the effective filing date of claimed invention to administer the peptide amphiphile lipid micelle (PALM) comprising paclitaxel of Elliott to patients with CIPN and CIPN associated with paclitaxel (neurotoxic chemotherapy) in view of Zang. One of ordinary skill in the art would have been motivated to administer Elliott’s peptide amphiphile micellar paclitaxel formulation to patients with, or at risk of paclitaxel induced CPN because Zang provides a clear rationale that encapsulating in nanoparticle systems reduces its neurotoxicity while maintaining anticancer efficacy. Elliott’s PALM system already embodies such a nanoparticle platform and teaches the same therapeutic agent. One of ordinary skill in in the art would have had a reasonable expectation of success in achieving the desired outcome-reduction in CIPN-because both references demonstrate that paclitaxel retains antitumor activity when delivered in micellar or liposomal carriers and that nanoparticle encapsulation attenuates does limiting neurotoxicity. Therefore, it would have been obvious to combine the composition of Elliott with the therapeutic context taught by Zang to arrive at the claimed method with a reasonable expectation that the resulting treatment would reduce paclitaxel inducing peripheral neuropathy while treating cancer.
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 67-76 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of US Patent No. 10532105 (reference application) in view of Zang (Journal of Controlled Release 303 (June, 2019) 109–116) and Elliott (WO2017011312 A1, cited previously) as evidenced by Budhan (see above reference).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims A method for reducing Chemotherapy-Induced Peripheral Neuropathy (CIPN) in a patient being treated for cancer with paclitaxel and which patient experiences paclitaxel induced CIPN, which method comprises: a) identifying a patient having CIPN associated with treatment for cancer; b) treating said cancer in said identified patient with an intravenous administration of an effective amount of an aqueous suspension which suspension comprises a therapeutically effective amount of peptide amphiphile lipid micellular nanoparticles, wherein said peptide amphiphile lipid micellular nanoparticles comprise:i) an amphiphilic peptide selected from SEQ ID No: 25, SEQ ID No 28, SEQ ID No 34, SEQ ID No 35 and SEQ ID No 36 wherein said amphiphilic peptide of said peptide amphiphile lipid micellular nanoparticles binds to the SR-B 1 receptor on tumor cells, said tumor cells associated with said cancer;ii) a lipid component comprising sphingomyelin and one or more additional phospholipids wherein said one or more additional phospholipids are selected from phosphatidylcholine, phosphatidylpolyethylene, glycol-phosphalidylethanol-amine, phosphatidyl- ethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidy linositol, cardiolipin, and any combination thereof; andiii) an effective amount of a conjugate selected from the group consisting of
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….and wherein said treatment reduces CIPN in said patient as compared to treatment with paclitaxel in the absence of said aqueous suspension.
The instant application further claims “wherein said patient suffers from CIPN of grade 1 or higher; wherein said patient suffers from grade 3 or grade 4 CIPN; wherein said reduction in CIPN also reduces pain associated with CIPN; wherein the lipid component comprises a single additional phospholipid which additional phospholipid is 1-palmitoyl-2- oleoyl phosphatidyl choline; wherein said aqueous suspension is a sterile aqueous suspension; wherein said sterile aqueous suspension is reconstituted from a lyophilized composition of peptide amphiphile lipid micelle nanoparticles; wherein said amphiphilic peptide has the amino acid sequence of SEQ ID NO: 35; wherein said cancer is ovarian cancer (see claims 68-76).
US Patent NO. 10532105B2 claims “A peptide comprising SEQ ID NO:35” (Claims 1-2 which falls within the scope of the peptides of the instant claims. US Patent NO. 10532105B2 further claims A Palm comprising said peptide and a lipid component comprising sphingomyelin and one or more additional phospholipid (see claim 3); PC (see claim 4); cargo molecule is a conjugate having the formula (I): A-R-L-X(formula I), wherein A is an agent having a hydroxyl or an amine group R; L is a linker; and X is an anchor moiety selected from the group consisting of cholesterol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, and δ-tocotrienol (claim 8); agent is paclitaxel (claim 13); treating a disorder (claim 20) which would be cancer (claim 15, anti-cancer, and a main utility, all examples are cancer including ovarian cancer); the anchor being tocotrienol and the bond being carbamate ester (see claims 9-10). US Patent NO. 10532105B2 teaches treating a disorder, in a patient comprising administering the same PALM-cargo of the instant claims which comprise the anti-cancer drug/chemo paclitaxel. US Patent NO. 10532105B is silent to wherein the patient has CIPN and CIPN associated with paclitaxel treatment for cancer and in particular ovarian cancer and treating grades 1, 3 or 4 of CIPN.
However, Zang teaches “Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior efficacy and safety profiles for other drugs” (see abstract). Zang teaches that paclitaxel has been discontinued in cancer treatments due to grade 2-3 peripheral neuropathy (see Discussion, paragraph 3). Zang teaches “liposomes containing paclitaxel were successfully developed and demonstrated reduced neurotoxicity in-vitro in neuronal cells and prevented development of peripheral neuropathy in-vivo. This proof of concept study showed that formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs” (see Abstract, conclusion).
It would have been obvious before the effective filing date of claimed invention to administer the peptide amphiphile lipid micelle (PALM) comprising paclitaxel of US Patent No. ‘105 to cancer patients with CIPN and CIPN associated with paclitaxel (neurotoxic chemotherapy) in view of Zang. One of ordinary skill in the art would have been motivated to administer US Patent No. ‘105s peptide amphiphile micellar paclitaxel formulation to cancer patients with, or at risk of paclitaxel induced CPN because Zang provides a clear rationale that encapsulating in nanoparticle systems reduces its neurotoxicity while maintaining anticancer efficacy. US Patent No. ‘105s PALM system already embodies such a nanoparticle platform and teaches the same therapeutic agent. One of ordinary skill in in the art would have had a reasonable expectation of success in achieving the desired outcome-reduction in CIPN-because both references demonstrate that paclitaxel retains antitumor activity when delivered in micellar or liposomal carriers and that nanoparticle encapsulation attenuates does limiting neurotoxicity. Therefore, it would have been obvious to combine the composition of US Patent No. ‘105 with the therapeutic context taught by Zang to arrive at the claimed method with a reasonable expectation that the resulting treatment would reduce paclitaxel inducing peripheral neuropathy while treating cancer.
Regarding the limitation of “wherein said method further reduces the pain associated with CIPN” found in instant claims 67, 70, US Patent No. ‘105 in view of Zang teach the same method of the instant claims including administering the same formulation to the same patient population (cancer patients with CIPN) and thus, the effects will inherently be achieved as a result of practicing the method of US Patent No. ‘105 in view of Zang.
Regarding claim 71, US patent No. ‘105 claims wherein the phospholipid is phosphatidylcholine and the one utilized was POPC (see claim 4). Furthermore, the compounds of instant claims 67 are encompassed by US Patent No. ‘105 (claims 8-17); instant SEQ ID NO:35 is identical to US Patent No. ‘105 SEQ ID NO:35 (see Table 2).
Regarding claim 72, Elliott teaches treatment using Peptide Amphiphile Lipid Micelle comprising Paclitaxel Cholesteryl Carbonate (XC) (the same peptide lipid micellular particles of the instant claims) wherein the cancer type is ovarian cancer (see Example 18, Ovarian cancer cells). It would have been obvious before the effective filing date of the claimed invention to also treat ovarian cancer patients with the compositions of US Patent No. ‘105 given that Elliott specifically teaches use of the same PALM comprising paclitaxel of US Patent No. ‘105 for treating ovarian cancer and paclitaxel is well known in the art to be useful chemotherapeutic for treating ovarian cancer.
Instant claims 68-69 further limit the method to patients having specified CIPN severity grades. Zang teaches paclitaxel induced CIPN and its clinical evaluation and severity assessment. CIPN severity grading is a well-established and routinely used clinical framework with a finite number of recognized categories (see Buduhan) used to guide treatment decisions. Once the problem of paclitaxel induced CIPN and the solution of nanoparticle paclitaxel delivery are taught, it would have been obvious before the effective filing date of the claimed invention to select a treatment threshold based on severity grade, including treating patients beginning at grade 1 or limiting treatment to more severe grades 3-4, as these represent identified and predictable options within the established grading system. This constitutes choosing from a finite number of predictable solutions with a reasonable expectation of success (the prior art combination teaches CIPN (including grade 2-3) is caused by paclitaxel and encapsulated liposomal paclitaxel reducing or prevented CIPN) and therefore is obvious to try under KSR and MPEP2143 (E). Furthermore, such selection represents routine optimization of a result effective clinical variable as described in MPEP 2144.
Regarding “identifying a patient having CIPN associated with treatment for cancer”, US Patent No. ‘105 in view of Elliott and Zang render obvious this step. Zang teaches that CIPN is a known adverse effect of paclitaxel and that nanoparticle paclitaxel formulations are used to reduce such neuropathy. A person of ordinary skill in the art would have been motivated to identify patients experiencing paclitaxel associated CIPN in order to administer the known nanoparticle formulation intended to reduce toxicity, which is the predictable clinical application of the combined teachings (see MPEP 2143).
Response to Applicant’s Arguments
Applicant notes the double patenting rejection and will address it when the claims are in condition for allowance, potentially by filing a terminal disclaimer, if appropriate. Applicant notes that the double patenting rejection relies on Elliott and Zang, which carry various deficiencies with respect to § 103 analysis for the reasons discussed above.
Applicants arguments have been fully considered but not found persuasive. Applicant does not substantively traverse the provisional nonstatutory obviousness type double patenting rejection, but instead indicates that the rejection may be addressed by filing a terminal disclaimer if appropriate. To the extent Applicant asserts that the rejection suffers from the same alleged deficiencies as the 103 rejection, such arguments are unpersuasive for the reasons discussed above with respect to the obviousness rejection. Applicant has not identified a meaningful distinction that would render the presently claimed subject matter patentably distinct from the claims of US Patent No. 10532105. Accordingly, the rejection is maintained.
Claims 67-76 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of Co-pending 18/041289 (reference application) in view of Zang (Journal of Controlled Release 303 (June, 2019) 109–116) and Elliott (WO2017011312 A1, cited previously) as evidenced by Budhan (see above reference).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims A method for reducing Chemotherapy-Induced Peripheral Neuropathy (CIPN) in a patient being treated for cancer with paclitaxel and which patient experiences paclitaxel induced CIPN, which method comprises: a) identifying a patient having CIPN associated with treatment for cancer; b) treating said cancer in said identified patient with an intravenous administration of an effective amount of an aqueous suspension which suspension comprises a therapeutically effective amount of peptide amphiphile lipid micellular nanoparticles, wherein said peptide amphiphile lipid micellular nanoparticles comprise:i) an amphiphilic peptide selected from SEQ ID No: 25, SEQ ID No 28, SEQ ID No 34, SEQ ID No 35 and SEQ ID No 36 wherein said amphiphilic peptide of said peptide amphiphile lipid micellular nanoparticles binds to the SR-B 1 receptor on tumor cells, said tumor cells associated with said cancer;ii) a lipid component comprising sphingomyelin and one or more additional phospholipids wherein said one or more additional phospholipids are selected from phosphatidylcholine, phosphatidylpolyethylene, glycol-phosphalidylethanol-amine, phosphatidyl- ethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidy linositol, cardiolipin, and any combination thereof; andiii) an effective amount of a conjugate selected from the group consisting of
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….and wherein said treatment reduces CIPN in said patient as compared to treatment with paclitaxel in the absence of said aqueous suspension.
The instant application further claims “wherein said patient suffers from CIPN of grade 1 or higher; wherein said patient suffers from grade 3 or grade 4 CIPN; wherein said reduction in CIPN also reduces pain associated with CIPN; wherein the lipid component comprises a single additional phospholipid which additional phospholipid is 1-palmitoyl-2- oleoyl phosphatidyl choline; wherein said aqueous suspension is a sterile aqueous suspension; wherein said sterile aqueous suspension is reconstituted from a lyophilized composition of peptide amphiphile lipid micelle nanoparticles; wherein said amphiphilic peptide has the amino acid sequence of SEQ ID NO: 35; wherein said cancer is ovarian cancer (see claims 68-76).
Co-pending Application 18/041289 claims “A peptide-amphiphile lipid micelle (PALM) comprising a peptide according to any one of claimsclaim1, and a lipid component comprising sphingomyelin and one or more additional phospholipids” (Claim 8). Co-pending Application 18/041289 further claims wherein the peptide is SEQ IDNO:7 which is identical to instant SEQ ID NO:36 (see claim 29); wherein the compound is paclitaxel 2 tocotrienyl carbonate (see claim 26); for treating ovarian cancer (Claim 37); anchor moiety of tocotrienol (claim 19); POPC as the phospholipid (see claims 10-11). Co-pending Application 18/041289 is silent to wherein the patient has CIPN and CIPN associated with paclitaxel treatment for cancer, treating grades 1, 3 or 4 of CIPN and sterile aqueous suspensions.
However, Zang teaches “Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior efficacy and safety profiles for other drugs” (see abstract). Zang teaches that paclitaxel has been discontinued in cancer treatments due to grade 2-3 peripheral neuropathy (see Discussion, paragraph 3). Zang teaches “liposomes containing paclitaxel were successfully developed and demonstrated reduced neurotoxicity in-vitro in neuronal cells and prevented development of peripheral neuropathy in-vivo. This proof of concept study showed that formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs” (see Abstract, conclusion).
It would have been obvious before the effective filing date of claimed invention to administer the peptide amphiphile lipid micelle (PALM) comprising paclitaxel of Co-pending Application 18/041289 to cancer patients with CIPN and CIPN associated with paclitaxel (neurotoxic chemotherapy) in view of Zang. One of ordinary skill in the art would have been motivated to administer Co-pending Application 18/041289 peptide amphiphile micellar paclitaxel formulation to cancer patients with, or at risk of paclitaxel induced CPN because Zang provides a clear rationale that encapsulating in nanoparticle systems reduces its neurotoxicity while maintaining anticancer efficacy. Co-pending Application 18/041289 PALM system already embodies such a nanoparticle platform and teaches the same therapeutic agent. One of ordinary skill in in the art would have had a reasonable expectation of success in achieving the desired outcome-reduction in CIPN-because both references demonstrate that paclitaxel retains antitumor activity when delivered in micellar or liposomal carriers and that nanoparticle encapsulation attenuates does limiting neurotoxicity. Therefore, it would have been obvious to combine the composition of Co-pending Application 18/041289 with the therapeutic context taught by Zang to arrive at the claimed method with a reasonable expectation that the resulting treatment would reduce paclitaxel inducing peripheral neuropathy while treating cancer.
Regarding the limitation of “wherein said method further reduces the pain associated with CIPN” found in instant claims 67, 70, Co-pending Application 18/041289 in view of Zang teach the same method of the instant claims including administering the same formulation to the same patient population (cancer patients with CIPN) and thus, the effects will inherently be achieved as a result of practicing the method of Co-pending Application 18/041289 in view of Zang.
Regarding claim 72-74, Elliott teaches treatment using Peptide Amphiphile Lipid Micelle comprising Paclitaxel Cholesteryl Carbonate (XC) (the same peptide lipid micellular particles of the instant claims) wherein the cancer type is ovarian cancer (see Example 18, Ovarian cancer cells). Elliott teaches wherein the PALM lyophilizate is reconstituted (in water, aqueous) and then sterilized (see paragraph 00121). Elliott teaches wherein the peptide in the PALM consists of instant SEQ ID NO:35 (see Claim 39 of Elliott) and intravenous administration (see paragraph 00125).
It would have been obvious before the effective filing date of the claimed invention sterilize the formulation of Co-pending Application 18/041289 for treating cancer patients because Elliott teaches the same PALM and further teaches that the formulation is sterilized prior to administration. Sterilization is a routine and standard procedure for administering pharmaceutical formulations and would have been an obvious modification using a known technique to improve safety and suitability in pharmaceutical formulations (see MPEP 2143).
Instant claims 68-69 further limit the method to patients having specified CIPN severity grades. Zang teaches paclitaxel induced CIPN and its clinical evaluation and severity assessment. CIPN severity grading is a well-established and routinely used clinical framework with a finite number of recognized categories (see Buduhan) used to guide treatment decisions. Once the problem of paclitaxel induced CIPN and the solution of nanoparticle paclitaxel delivery are taught, it would have been obvious before the effective filing date of the claimed invention to select a treatment threshold based on severity grade, including treating patients beginning at grade 1 or limiting treatment to more severe grades 3-4, as these represent identified and predictable options within the established grading system. This constitutes choosing from a finite number of predictable solutions with a reasonable expectation of success (the prior art combination teaches CIPN (including grade 2-3) is caused by paclitaxel and encapsulated liposomal paclitaxel reducing or prevented CIPN) and therefore is obvious to try under KSR and MPEP2143 (E). Furthermore, such selection represents routine optimization of a result effective clinical variable as described in MPEP 2144.
Regarding “identifying a patient having CIPN associated with treatment for cancer”, Co-pending Application 18/041289 in view of Elliott and Zang render obvious this step. Zang teaches that CIPN is a known adverse effect of paclitaxel and that nanoparticle paclitaxel formulations are used to reduce such neuropathy. A person of ordinary skill in the art would have been motivated to identify patients experiencing paclitaxel associated CIPN in order to administer the known nanoparticle formulation intended to reduce toxicity, which is the predictable clinical application of the combined teachings (see MPEP 2143).
Response to Applicant’s Arguments
Applicant notes the double patenting rejection and will address it when the claims are in condition for allowance, potentially by filing a terminal disclaimer, if appropriate. Applicant notes that the double patenting rejection relies on Elliott and Zang, which carry various deficiencies with respect to § 103 analysis for the reasons discussed above.
Applicants arguments have been fully considered but not found persuasive. Applicant does not substantively traverse the provisional nonstatutory obviousness type double patenting rejection, but instead indicates that the rejection may be addressed by filing a terminal disclaimer if appropriate. To the extent Applicant asserts that the rejection suffers from the same alleged deficiencies as the 103 rejection, such arguments are unpersuasive for the reasons discussed above with respect to the obviousness rejection. Applicant has not identified a meaningful distinction that would render the presently claimed subject matter patentably distinct from the claims of Co pending 18/041289. Accordingly, the rejection is maintained.
Claims 67-76 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-47 of Co-pending 19/204092 (reference application) in view of Zang (Journal of Controlled Release 303 (June, 2019) 109–116) as evidenced by Budhan (see above reference).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims A method for reducing Chemotherapy-Induced Peripheral Neuropathy (CIPN) in a patient being treated for cancer with paclitaxel and which patient experiences paclitaxel induced CIPN, which method comprises: a) identifying a patient having CIPN associated with treatment for cancer; b) treating said cancer in said identified patient with an intravenous administration of an effective amount of an aqueous suspension which suspension comprises a therapeutically effective amount of peptide amphiphile lipid micellular nanoparticles, wherein said peptide amphiphile lipid micellular nanoparticles comprise:i) an amphiphilic peptide selected from SEQ ID No: 25, SEQ ID No 28, SEQ ID No 34, SEQ ID No 35 and SEQ ID No 36 wherein said amphiphilic peptide of said peptide amphiphile lipid micellular nanoparticles binds to the SR-B 1 receptor on tumor cells, said tumor cells associated with said cancer;ii) a lipid component comprising sphingomyelin and one or more additional phospholipids wherein said one or more additional phospholipids are selected from phosphatidylcholine, phosphatidylpolyethylene, glycol-phosphalidylethanol-amine, phosphatidyl- ethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidy1 linositol, cardiolipin, and any combination thereof; andiii) an effective amount of a conjugate selected from the group consisting of
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….and wherein said treatment reduces CIPN in said patient as compared to treatment with paclitaxel in the absence of said aqueous suspension.
The instant application further claims “wherein said patient suffers from CIPN of grade 1 or higher; wherein said patient suffers from grade 3 or grade 4 CIPN; wherein said reduction in CIPN also reduces pain associated with CIPN; wherein the lipid component comprises a single additional phospholipid which additional phospholipid is 1-palmitoyl-2- oleoyl phosphatidyl choline; wherein said aqueous suspension is a sterile aqueous suspension; wherein said sterile aqueous suspension is reconstituted from a lyophilized composition of peptide amphiphile lipid micelle nanoparticles; wherein said amphiphilic peptide has the amino acid sequence of SEQ ID NO: 35; wherein said cancer is ovarian cancer (see claims 68-76).
Co-pending Application 19/204092 claims miceller nanoparticles comprising instant SEQ ID NO:35, sphingomyelin, POPC, a conjugate comprising an anchor moiety and a chemotherapeutic (see claims 1, 46). Co-pending Application 19/204092 further claims treating ovarian cancer (see claim 32-34), paclitaxel carbonate conjugates that fall in scope with the instant claims (see claim 17); sterilized lyophilized formulations (claims 1, 6, 24).
Co-pending Application 19/204092 is silent to wherein the patient has CIPN and CIPN associated with paclitaxel treatment for cancer, treating grades 1, 3 or 4 of CIPN.
However, Zang teaches “Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior efficacy and safety profiles for other drugs” (see abstract). Zang teaches that paclitaxel has been discontinued in cancer treatments due to grade 2-3 peripheral neuropathy (see Discussion, paragraph 3). Zang teaches “liposomes containing paclitaxel were successfully developed and demonstrated reduced neurotoxicity in-vitro in neuronal cells and prevented development of peripheral neuropathy in-vivo. This proof of concept study showed that formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs” (see Abstract, conclusion).
It would have been obvious before the effective filing date of claimed invention to administer the peptide amphiphile lipid micelle (PALM) comprising paclitaxel of Co-pending Application 19/204092 to cancer patients with CIPN and CIPN associated with paclitaxel (neurotoxic chemotherapy) in view of Zang. One of ordinary skill in the art would have been motivated to administer Co-pending Application 19/204092 peptide amphiphile micellar paclitaxel formulation to cancer patients with, or at risk of paclitaxel induced CPN because Zang provides a clear rationale that encapsulating in nanoparticle systems reduces its neurotoxicity while maintaining anticancer efficacy. Co-pending Application 19/204092 PALM system already embodies such a nanoparticle platform and teaches the same therapeutic agent. One of ordinary skill in in the art would have had a reasonable expectation of success in achieving the desired outcome-reduction in CIPN-because both references demonstrate that paclitaxel retains antitumor activity when delivered in micellar or liposomal carriers and that nanoparticle encapsulation attenuates does limiting neurotoxicity. Therefore, it would have been obvious to combine the composition of Co-pending Application 19/204092 with the therapeutic context taught by Zang to arrive at the claimed method with a reasonable expectation that the resulting treatment would reduce paclitaxel inducing peripheral neuropathy while treating cancer.
Regarding the limitation of “wherein said method further reduces the pain associated with CIPN” found in instant claims 67, 70, Co-pending Application 19/204092 in view of Zang teach the same method of the instant claims including administering the same formulation to the same patient population (cancer patients with CIPN) and thus, the effects will inherently be achieved as a result of practicing the method of Co-pending Application 19/204092 in view of Zang.
Instant claims 68-69 further limit the method to patients having specified CIPN severity grades. Zang teaches paclitaxel induced CIPN and its clinical evaluation and severity assessment. CIPN severity grading is a well-established and routinely used clinical framework with a finite number of recognized categories (see Buduhan) used to guide treatment decisions. Once the problem of paclitaxel induced CIPN and the solution of nanoparticle paclitaxel delivery are taught, it would have been obvious before the effective filing date of the claimed invention to select a treatment threshold based on severity grade, including treating patients beginning at grade 1 or limiting treatment to more severe grades 3-4, as these represent identified and predictable options within the established grading system. This constitutes choosing from a finite number of predictable solutions with a reasonable expectation of success (the prior art combination teaches CIPN (including grade 2-3) is caused by paclitaxel and encapsulated liposomal paclitaxel reducing or prevented CIPN) and therefore is obvious to try under KSR and MPEP2143 (E). Furthermore, such selection represents routine optimization of a result effective clinical variable as described in MPEP 2144.
Regarding “identifying a patient having CIPN associated with treatment for cancer”, Co-pending Application 19/204092 in view of Zang render obvious this step. Zang teaches that CIPN is a known adverse effect of paclitaxel and that nanoparticle paclitaxel formulations are used to reduce such neuropathy. A person of ordinary skill in the art would have been motivated to identify patients experiencing paclitaxel associated CIPN in order to administer the known nanoparticle formulation intended to reduce toxicity, which is the predictable clinical application of the combined teachings (see MPEP 2143).
Response to Applicant’s Arguments
Applicant notes the double patenting rejection and will address it when the claims are in condition for allowance, potentially by filing a terminal disclaimer, if appropriate. Applicant notes that the double patenting rejection relies on Elliott and Zang, which carry various deficiencies with respect to § 103 analysis for the reasons discussed above.
Applicants arguments have been fully considered but not found persuasive. Applicant does not substantively traverse the provisional nonstatutory obviousness type double patenting rejection, but instead indicates that the rejection may be addressed by filing a terminal disclaimer if appropriate. To the extent Applicant asserts that the rejection suffers from the same alleged deficiencies as the 103 rejection, such arguments are unpersuasive for the reasons discussed above with respect to the obviousness rejection. Applicant has not identified a meaningful distinction that would render the presently claimed subject matter patentably distinct from the claims of Co pending 19/204092. Accordingly, the rejection is maintained.
Claims 67-76 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of Co-pending 19/204171 (reference application) in view of Zang (Journal of Controlled Release 303 (June, 2019) 109–116) and Elliott (WO2017011312 A1, cited previously) as evidenced by Budhan (see above reference).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims A method for reducing Chemotherapy-Induced Peripheral Neuropathy (CIPN) in a patient being treated for cancer with paclitaxel and which patient experiences paclitaxel induced CIPN, which method comprises: a) identifying a patient having CIPN associated with treatment for cancer; b) treating said cancer in said identified patient with an intravenous administration of an effective amount of an aqueous suspension which suspension comprises a therapeutically effective amount of peptide amphiphile lipid micellular nanoparticles, wherein said peptide amphiphile lipid micellular nanoparticles comprise:i) an amphiphilic peptide selected from SEQ ID No: 25, SEQ ID No 28, SEQ ID No 34, SEQ ID No 35 and SEQ ID No 36 wherein said amphiphilic peptide of said peptide amphiphile lipid micellular nanoparticles binds to the SR-B 1 receptor on tumor cells, said tumor cells associated with said cancer;ii) a lipid component comprising sphingomyelin and one or more additional phospholipids wherein said one or more additional phospholipids are selected from phosphatidylcholine, phosphatidylpolyethylene, glycol-phosphalidylethanol-amine, phosphatidyl- ethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidy linositol, cardiolipin, and any combination thereof; andiii) an effective amount of a conjugate selected from the group consisting of
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….and wherein said treatment reduces CIPN in said patient as compared to treatment with paclitaxel in the absence of said aqueous suspension.
The instant application further claims “wherein said patient suffers from CIPN of grade 1 or higher; wherein said patient suffers from grade 3 or grade 4 CIPN; wherein said reduction in CIPN also reduces pain associated with CIPN; wherein the lipid component comprises a single additional phospholipid which additional phospholipid is 1-palmitoyl-2- oleoyl phosphatidyl choline; wherein said aqueous suspension is a sterile aqueous suspension; wherein said sterile aqueous suspension is reconstituted from a lyophilized composition of peptide amphiphile lipid micelle nanoparticles; wherein said amphiphilic peptide has the amino acid sequence of SEQ ID NO: 35; wherein said cancer is ovarian cancer (see claims 68-76).
Co-pending Application 19/204171 claims an aqueous composition comprising HDL mimetic nanoparticles which comprises sphingomyelin, Phosphatidylcholine, a conjugate comprising an anchor moiety and paclitaxel and SEQ ID NO:35 which is identical to instant SEQ ID NO:35 (see claims 1-2). Co-pending Application 19/204171 claims treating cancer, including SR B1 overexpressing cancers (see claims 21 and 23), ovarian cancer (Claim 23).
Co-pending Application 19/204171 is silent to wherein the patient has CIPN and CIPN associated with paclitaxel treatment for cancer, treating grades 1, 3 or 4 of CIPN and sterile aqueous suspensions.
However, Zang teaches “Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior efficacy and safety profiles for other drugs” (see abstract). Zang teaches that paclitaxel has been discontinued in cancer treatments due to grade 2-3 peripheral neuropathy (see Discussion, paragraph 3). Zang teaches “liposomes containing paclitaxel were successfully developed and demonstrated reduced neurotoxicity in-vitro in neuronal cells and prevented development of peripheral neuropathy in-vivo. This proof of concept study showed that formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs” (see Abstract, conclusion).
It would have been obvious before the effective filing date of claimed invention to administer the peptide amphiphile lipid micelle (PALM) comprising paclitaxel of Co-pending Application 19/204171 to cancer patients with CIPN and CIPN associated with paclitaxel (neurotoxic chemotherapy) in view of Zang. One of ordinary skill in the art would have been motivated to administer Co-pending Application 19/204171 peptide amphiphile micellar paclitaxel formulation to cancer patients with, or at risk of paclitaxel induced CPN because Zang provides a clear rationale that encapsulating in nanoparticle systems reduces its neurotoxicity while maintaining anticancer efficacy. Co-pending Application 19/204171 PALM system already embodies such a nanoparticle platform and teaches the same therapeutic agent. One of ordinary skill in in the art would have had a reasonable expectation of success in achieving the desired outcome-reduction in CIPN-because both references demonstrate that paclitaxel retains antitumor activity when delivered in micellar or liposomal carriers and that nanoparticle encapsulation attenuates does limiting neurotoxicity. Therefore, it would have been obvious to combine the composition of Co-pending Application 19/204171 with the therapeutic context taught by Zang to arrive at the claimed method with a reasonable expectation that the resulting treatment would reduce paclitaxel inducing peripheral neuropathy while treating cancer.
Regarding the limitation of “wherein said method further reduces the pain associated with CIPN” found in instant claims 67, 70, Co-pending Application 19/204171 in view of Zang teach the same method of the instant claims including administering the same formulation to the same patient population (cancer patients with CIPN) and thus, the effects will inherently be achieved as a result of practicing the method of Co-pending Application 19/204171 in view of Zang.
Regarding claim 72-74, Elliott teaches treatment using Peptide Amphiphile Lipid Micelle comprising Paclitaxel Cholesteryl Carbonate (XC) (the same peptide lipid micellular particles of the instant claims) wherein the cancer type is ovarian cancer (see Example 18, Ovarian cancer cells). Elliott teaches wherein the PALM lyophilizate is reconstituted (in water, aqueous) and then sterilized (see paragraph 00121). Elliott teaches wherein the peptide in the PALM consists of instant SEQ ID NO:35 (see Claim 39 of Elliott) and intravenous administration (see paragraph 00125).
It would have been obvious before the effective filing date of the claimed invention sterilize the formulation of Co-pending Application 19/204171 for treating cancer patients because Elliott teaches the same PALM and further teaches that the formulation is sterilized prior to administration. Sterilization is a routine and standard procedure for administering pharmaceutical formulations and would have been an obvious modification using a known technique to improve safety and suitability in pharmaceutical formulations (see MPEP 2143).
Instant claims 68-69 further limit the method to patients having specified CIPN severity grades. Zang teaches paclitaxel induced CIPN and its clinical evaluation and severity assessment. CIPN severity grading is a well-established and routinely used clinical framework with a finite number of recognized categories (see Buduhan) used to guide treatment decisions. Once the problem of paclitaxel induced CIPN and the solution of nanoparticle paclitaxel delivery are taught, it would have been obvious before the effective filing date of the claimed invention to select a treatment threshold based on severity grade, including treating patients beginning at grade 1 or limiting treatment to more severe grades 3-4, as these represent identified and predictable options within the established grading system. This constitutes choosing from a finite number of predictable solutions with a reasonable expectation of success (the prior art combination teaches CIPN (including grade 2-3) is caused by paclitaxel and encapsulated liposomal paclitaxel reducing or prevented CIPN) and therefore is obvious to try under KSR and MPEP2143 (E). Furthermore, such selection represents routine optimization of a result effective clinical variable as described in MPEP 2144.
Response to Applicant’s Arguments
Applicant notes the double patenting rejection and will address it when the claims are in condition for allowance, potentially by filing a terminal disclaimer, if appropriate. Applicant notes that the double patenting rejection relies on Elliott and Zang, which carry various deficiencies with respect to § 103 analysis for the reasons discussed above.
Applicants arguments have been fully considered but not found persuasive. Applicant does not substantively traverse the provisional nonstatutory obviousness type double patenting rejection, but instead indicates that the rejection may be addressed by filing a terminal disclaimer if appropriate. To the extent Applicant asserts that the rejection suffers from the same alleged deficiencies as the 103 rejection, such arguments are unpersuasive for the reasons discussed above with respect to the obviousness rejection. Applicant has not identified a meaningful distinction that would render the presently claimed subject matter patentably distinct from the claims of Co-pending Application 19/204171. Accordingly, the rejection is maintained.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654
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