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
Continued Examination under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 of RCE on February 2, 2026 and amendment after final filed on February 2, 2026 has been entered. Claims 1-66 are canceled and new claims 67-76 are pending in the instant application.
The restriction requirement was deemed proper and made FINAL in a previous office action. Claims 67-76 are pending in the instant application.
Withdrawn Rejections
The objections to claims 64, 66, 55 are withdrawn in view of cancelation of the claims filed February 2, 2026.
The rejection of claims 55-66 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of cancelation of the claims filed February 2, 2026.
The rejection of Claim(s) 55-66 are 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Elliott (WO2017011312 A1, cited previously) in view of Zang (Journal of Controlled Release 303 (June, 2019) 109–116) is withdrawn in view of cancelation of the claims filed February 2, 2026.
The rejection of Claims 55-66 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of Zang (Journal of Controlled Release 303 (June, 2019) 109–116) and Elliott (WO2017011312 A1, cited previously) is withdrawn in view of cancelation of the claims filed February 2, 2026.
New Objection
Claim 67 is objected to for the following informality: the acronym “SR-B1” should be spelled out in its first instance. For example, “scavenger receptor class B type 1 (SR-B1)”.
New Rejections
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 67-76 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.
Claim 67 recites “a patient being treated for cancer” and later recites “step (a) “identifying a patient having CIPN associated with treatment for cancer”, followed by step (b) “treating said cancer in said identified patient” and i) ….”with said cancer”. It is unclear whether the “patient” identified in step (a) is the same patient introduced earlier, and the phrase “said cancer” lacks clear antecedent basis tied to the identified patient. A suggested amendment is as follows “A method for reducing CIPN in a patient being treated for cancer with paclitaxel, the method comprising: (a) identifying the patient as having CIPN associated with the paclitaxel treatment and; (b) treating the cancer in the identified patient by….” Claims 68-76 are also rejected due to their dependence on claim 67 and not clarifying this point of confusion.
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 are 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).
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.
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 are 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).
Claims 67-76 are 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. Sterilzation 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).
Claims 67-76 are 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, 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 19/204092 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).
Claims 67-76 are 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, Phosphtaidylcholine, 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. Sterilzation 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 19/204171 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).
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654