Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 05/21/2025 has been entered.
DETAILED ACTION
Claims 67-69 and 72-86 are pending in the Claim Set filed 5/21/2025.
Claims 67 and 73 have been amended.
Claim 1-66, 70 and 71 are canceled.
Applicants elected Group I: claims 67-82, in the reply filed on 12/21/2023. Further, Applicants’ elected species is as follows: (i) PLA-PEG-PPG-PEG-PLA penta block copolymer (claims 67 and 69); and (ii) anti-cancer peptide: CQCRRKN (SEQ ID NO: 2; claim 81).
Claims 68, 80 and 82-86 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Herein, claims 67, 69, 72-79 and 81 are for examination to the extent that they read on the elected species.
Withdrawn Objections/Rejections
The rejection of claims 67, 69, 72-79 and 81 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applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention regarding a single particle is withdrawn in view of the claim amendments.
The rejection of claims 73, 74, 75 and 81 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 regarding insufficient antecedent basis for this limitation in the claim, because the phrase: the therapeutic agent, is withdrawn in view of the claim amendments.
The rejection of claims 67, 69, 73, 77, 78 and 79 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Xiong et al (Synthesis and Aggregation Behavior of Pluronic F127/Poly(lactic acid) Block Copolymers in Aqueous Solutions, p.9979, 2003) in view of Fetzer et al (WO2012024530, cited in IDS filed 1/19/2024) is withdrawn in favor of the new grounds of rejections as set forth below.
The rejection of claims 67, 69, 72-79 and 81 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 11-15 and 18 of U.S. Patent No. 11,246,904 (herein ‘904) in view of Fetzer et al (WO2012024530, cited in IDS filed 1/19/2024) s withdrawn.
Claim Objections
Claims 75 and 77 are objected to because of the following grammatical informalities:
Claim 75 recites “the peptide”, however claim 74 from which claim 75 depends, recites: peptides (i.e., plural).
For claim language consistency, Applicants should amend claim 75 to recite: “wherein the peptides are selected from the group consisting of anticancer or insulin peptides”.
Claim 77 is objected to for grammatical completeness of the claims. The phrase ‘any one of’ should be deleted from claim 77.
Appropriate correction is required.
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.
Claim 79 is 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 pre-AIA the applicant regards as the invention.
The term "substantially" (i.e. substantially free of emulsifier) in claim 79 is a relative term which renders the claim indefinite. The term "substantially" is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Here, the term substantially in the claim renders the metes and bounds of the claims unclear, particularly as one cannot readily determine what numerical values meets the limitation for ‘substantially free of emulsifier.’
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) The claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 67, 69, 77, 78 and 79 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xiong et al (Synthesis and Aggregation Behavior of Pluronic F127/Poly(lactic acid) Block Copolymers in Aqueous Solutions, Macromolecules, p.9979, 2003, cited in IDS filed 1/06/2003).
Regarding claims 67, 69, 77, 78 and 79,
Xiong teaches poly(lactic acid) (PLA) were grafted to both ends of Pluronic F127 (PEO-PPO-PEO) to produce novel amphiphilic PLA-F127-PLA block copolymers (structure shown below, e.g., PLAF127-29) (Abstract; Figure 1):
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126
564
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where the structure (shown above) is PLA-PEG-PPG-PEG-PLA (i.e., PLA-PEO-PPO-PEO-PLA) that is a penta-block copolymer, of which is recited in claim 67 and claim 69. Further, Xiong teaches PLA is a biodegradable and biocompatible polyester (p.9980), so that PLA-F127-PLA block copolymers containing the PLA monomeric unit are biodegradable. Therefore, PLA-PEG-PPG-PEG-PLA (PLA-PEO-PPO-PEO-PLA) as taught by Xiong is a species of the claimed PLA-PEG-PPG-PEG-PLA penta block copolymer. See MPEPEP 2131.02. subsection I: A species will anticipate a claim to a genus. A generic claim cannot be allowed to an applicant if the prior art discloses a species falling within the claimed genus. The species in that case will anticipate the genus. In re Slayter, 276 F.2d 408, 411, 125 USPQ 345, 347 (CCPA 1960); In re Gosteli, 872 F.2d 1008, 10 USPQ2d 1614 (Fed. Cir. 1989).
Xiong teaches PLA-PEG-PPG-PEG-PLA, e.g., PLAF127-29, having an average molecular weight of 44,700 g/mol, wherein 67 wt% of PLAF127-29 is PLA. (See Table 1, p.9982). Therefore, PLAF127-29 block copolymer has PLA having an average molecular weight of about 30,000 g/mol, which lies within PLA has an average molecular weight of about 4000 to about 90,000 g/mole (recited in instant claim 77) and PLAF127-29 block copolymer has an average molecular weight of about 15,000 g/mol, which lies within PEG-PPG-PEG has an average molecular weight of about 4,000 to about 15,000 g/mole (recited in instant claim 77). Prior art which teaches a range overlapping or touching the claimed range anticipates if the prior art range discloses the claimed range with sufficient specificity. See MPEP 2131.03, subsection II.
Xiong teaches nanoparticles of PLA-F127-PLA having a diameter of about 100 nm (p,9982, right col.; Conclusion, p.9984), of which lies inside the diameter of the biodegradable polymer nanoparticles is in the range of about 10 to about 200 nm (as recited in claim 78). Moreover, Xiong teaches that the aggregation behaviors of the block copolymers in aqueous solutions were studied in detail by LLS and TEM. The diameter of PLA-F127-PLA aggregates was around 100 nm, wherein these systems exhibit desirable properties for potential applications as drug delivery vehicles (Abstract; Conclusions, right col., p.9984; See entire document). Prior art which teaches a range overlapping or touching the claimed range anticipates if the prior art range discloses the claimed range with sufficient specificity. See MPEP 2131.03, subsection II.
Xiong teaches aqueous solutions of PLA-F127-PLA (Figure.8; Sample Preparation, left col, p.9981) (i.e., substantially free of emulsifier: reads on Instant Claim 79).
Thus, Xiong teaches PLAF127-29 that is a species of the claimed biodegradable polymeric nanoparticles, so that it would necessarily follow that the PLAF127-29 biodegradable polymeric nanoparticles as taught by Xiong are suitable for delivery by intravenous injection.
There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (See MPEP 2112 II. Inherent feature need not be recognized at the relevant time). Furthermore, Xiong teaches that Pluronic block copolymers are chemically modified with PCL to lower the Critical micelle concentration (CMC) because the CMC of Pluronic block copolymers without this modification is typically too high for injection (See Introduction, left col. last para. to right col.).
Therefore, claims 67, 69, 77, 78 and 79 are anticipated by Xiong et al (Synthesis and Aggregation Behavior of Pluronic F127/Poly(lactic acid) Block Copolymers in Aqueous Solutions, p.9979, 2003).
Response to arguments
Applicants argue that one of ordinary skill in the art would not combine the teachings of Xiong and Fetzer to create PLA-PEG-PPG-PEG-PLA nanoparticles for IV administration with any expectation of success. Xiong does not teach IV administration of PLA-PEG-PPG-PEG-PLA block co-polymers. Fetzer does not teach PLA-PEG-PPG-PEG-PLA block co-polymers. Applicants argue that Fetzer focus on polymers comprising PEG and/or PLGA.1 Fetzer only teaches a PLA-PEG-PLA block co-polymer, an entirely different block co-polymer with a different structure than PLA-PEGPPG-PEG-PLA, in prophetic Example 8 of Fetzer.2 Applicant notes that Example 8 of Fetzer is prophetic; therefore, Fetzer does not even show that the PLA-PEG-PLA block co-polymer could be made, let alone IV administered. Furthermore, there is no teaching in Fetzer that the PLA-PEG-PLA co-polymer is IV administered, prophetic or otherwise.
Applicants’ arguments are moot in regards to Fetzer because the new ground of 35 U.S.C. 102(a)(1) rejection does not rely on the teachings of Fetzer in the rejections as set forth above.
Applicants’ arguments regarding Xiong are not persuasive, because on further consideration, Xiong teaches PLAF127-29 that is a species of the claimed biodegradable polymeric nanoparticles, so that it would necessarily follow that the PLAF127-29 biodegradable polymeric nanoparticles as disclosed by Xiong are suitable for delivery by intravenous injection. Furthermore, Xiong teaches that Pluronic copolymers are chemically modified with PCL to lower the CMC because the CMC of Pluronic block copolymers without this modification is typically too high for injection, see introduction.
Therefore, as fully discussed above, claims 67, 69, 77, 78 and 79 are anticipated by Xiong et al (Synthesis and Aggregation Behavior of Pluronic F127/Poly(lactic acid) Block Copolymers in Aqueous Solutions, p.9979, 2003).
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ
459 (1966), that are applied for establishing a background for determining
obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 67, 69, 72-79 and 81 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Xiong et al (Synthesis and Aggregation Behavior of Pluronic F127/Poly(lactic acid) Block Copolymers in Aqueous Solutions, Macromolecules, p.9979, 2003, cited in IDS filed 1/06/2003) in view of Gan et al (Release kinetics of hydrophobic and hydrophilic model drugs from pluronic F127/poly(lactic acid) nanoparticles, Journal of Controlled Release p.73, 2005) [Gan] and Kufe et al (US 2011/0251246, of record) [Kufe].
Regarding claims 67, 69, 77, 78 and 79, the teachings of Xiong are described above.
Xiong differs from the claims in that the document does not teach the biodegradable polymeric nanoparticles further comprise a therapeutic agent, wherein the therapeutic agent is encapsulated, surface conjugated, or adsorbed on the biodegradable polymeric nanoparticles, wherein the therapeutic agent is a peptide that is an anti-cancer peptide, wherein the anti-cancer peptide is CQCRRKN (elected therapeutic agent) and the nanoparticles further comprise a targeting moiety.
Regarding claims 72, 73, 74, 75, 76 and 81,
However, Gan and Kufe, as a whole, cure the deficiencies.
Gan teaches pluronic F127/poly(lactic acid) (i.e., penta block copolymer) form vesicles, wherein vesicles are excellent candidates for drug delivery because they can deliver both hydrophobic and hydrophilic drugs (p.74, left vol.’ Section 2.2. Syntheses of PLA–F127–PLA block copolymers, p.74, right col.; Section 2.3. In vitro release study, p.74). Particularly, Gan teaches drug loaded pluronic F127/poly(lactic acid) polymer aggregates (Section 2.3. In vitro release study, p.74). Gan teaches the hydrodynamic radii Rh of the aggregates formed from PLAF127-29 aqueous solutions are about 56 nm. Gan teaches for drug delivery applications, the preferred range of particle size is in the range of 10–100 nm, so that PLA–F127–PLA nanoparticles have potential applications in drug delivery systems, such that the PLA F127–PLA aggregates comprise the capability to deliver both hydrophobic and hydrophilic drugs due to the vesicular structure p.76, right col.). Moreover, Gan teaches that compared to normal core-shell micelles, vesicles with a hydrophilic core and hydrophobic layers are better drug delivery carriers because they are suitable to deliver not only hydrophobic but also hydrophilic drugs. Further, Gan teaches in clinical studies it is shown that vesicles can improve the treatment efficacy of anticancer drugs due to their enhanced permeability and retention properties (p.74, left col. top para.).
One skilled in the art at the time the claimed invention was made would have recognized at the time that pluronic F127/poly(lactic acid) nanoparticles can be used to encapsulate, surface conjugate, or adsorbed both hydrophobic and hydrophilic drugs due to the vesicular structure. One skilled in the art would have been motivated to provide PLA–F127–PLA nanoparticles as a drug delivery system to delivery varied drugs encompassing hydrophobic and also hydrophilic drugs because Gan teaches that PLA–F127–PLA nanoparticles form drug-polymer aggregates in the range of 10-100 nm having a reasonable expectation of success that is preferred particle sizes for drug delivery.
Kufe teaches an anti-cancer peptide comprising a sequence from the MUC I-CD: CQCRRKN (e.g., CQCRRKN: anti-cancer peptide) that is linked to a protein transduction domain such as polyarginine to facilitate entry of the peptide into cells (i.e., targeting moiety), wherein the MUC1-CD: CQCRRKN is fixed to a nanoparticle [0003]; [0006]; [0008]; [0014-0015; QCRRKN]; [0017]; Fig. 1A; Figs. 4A-E; selectivity of MUC1-CQC for MUC1 expressing breast cells [0038]; [0039]; [0052]; [0295]; See entire document). Further, Kufe teaches that short peptides comprising the CQC motif plays are able to disrupt MUCl oligomer formation, preventing transport into the nucleus of tumor cells. Further, Kufe teaches peptides comprising the CQC motif are able to inhibit tumor cell growth, as well as induce apoptosis in such cells and even necrosis of tumor tissue [0056]. Moreover, Kufe teaches administration of the compositions comprising the CQC motif by intravenous injection [[0189]. Additionally, Kufe discloses that there is an overexpression of MUC1 in most human carcinomas. Thus, it would have been prima facie obvious to one of skill in the art at the time the claimed invention was made to provide CQCRRKN (anti-cancer peptide) that is fixed to pluronic F127/poly(lactic acid) nanoparticles either by encapsulation, surface conjugation, and/or adsorbed thereon to treat cancer since CQCRRKN provides interference with MUNCI oligomer formation and are suitable for intravenous injection and further because Gan teaches that pluronic F127/poly(lactic acid) nanoparticles form vesicles that are preferred for drug delivery.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to provide pluronic F127/poly(lactic acid) nanoparticles (i.e., a species of the claimed PLA-PEG-PPG-PEG-PLA nanoparticles) for intravenous injection wherein the nanoparticles further comprise a therapeutic agent that is CQCRRKN of which is encapsulated, conjugated, and/or adsorbed on the F127/poly(lactic acid) nanoparticles wherein poly D-arginine (targeting moiety) is linked to CQCRRKN in order to facilitate the targeting of CQCRRKN (anti-cancer peptide) to cancer cells at the time the claimed invention was made.
All the claimed elements herein are known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention, where there is no unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art.
Therefore, in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of skill in the art at the time the claimed invention was made, as evidenced by Xiong, Gan and Kufe, as a whole.
Response to arguments
Applicants argue that the combination of Xiong and Fetzer do not teach or suggest PLA-PEG-PPG-PEG-PLA nanoparticles for IV administration. Kufe does not cure the deficiencies of Xiong and Fetzer. The Examiner has not explained why it would be obvious to administer PLA-PEG-PPG-PEG-PLA nanoparticles by IV administration in view of Kufe.
Applicant’s arguments have been fully considered but they are not persuasive, because Xiong teaches PLAF127-29 that is a species of the claimed PLA-PEG-PPG-PEG-PLA penta block biodegradable polymeric nanoparticles, so that it would necessarily follow that the PLAF127-29 biodegradable polymeric nanoparticles as taught by Xiong are suitable for delivery by intravenous injection.
Moreover, Applicants’ arguments are moot in regards to Fetzer because the new ground of 35 U.S.C. 102(a)(1) rejection does not rely on the teachings of Fetzer in the rejections a set forth above.
Further, the teachings of Kufe are directed to the PLAF127-29 biodegradable polymeric nanoparticles (i.e., identical penta block nanoparticles as taught by Xiong) that further comprise a therapeutic agent: CQCRRKN. Moreover, Kufe teaches CQCRRKN (i.e., comprising a CQC motif) disrupt MUCl oligomer formation and inhibits tumor cell growth, wherein overexpression of MUC1 is found in human carcinomas. Additionally, Kufe teaches administration of the compositions comprising the CQC motif by intravenous injection. Thus, it would have been prima facie obvious to one of skill in the art at the time the claimed invention was made to provide CQCRRKN (anti-cancer peptide) that is fixed to pluronic F127/poly(lactic acid) nanoparticles either by encapsulation, surface conjugation, and/or adsorbed thereon to treat cancer since CQCRRKN provides interference with MUNCI oligomer formation and are suitable for intravenous injection and further because Gan teaches that pluronic F127/poly(lactic acid) nanoparticles form vesicles that are preferred for drug delivery.
Also, Gan teaches pluronic F127/poly(lactic acid) nanoparticles form vesicles that are excellent candidates for drug delivery because they can deliver both hydrophobic and hydrophilic drugs. Further, Gan teaches in clinical studies that vesicles improve the treatment efficacy of anticancer drugs, due to vesicles comprising enhanced permeability and retention properties.
NEW GROUNDS of Double Patenting Rejections
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 67, 69, 72-79 and 81 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 11-15 and 18 of U.S. Patent No. 11,246,904 (herein ‘904) in view of Xiong et al (Synthesis and Aggregation Behavior of Pluronic F127/Poly(lactic acid) Block Copolymers in Aqueous Solutions, Macromolecules, p.9979, 2003, cited in IDS filed 1/06/2003).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant Claims are directed to a biodegradable polymeric nanoparticles comprising a PLA-PEG-PPG-PEG-PLA penta block copolymer, wherein the biodegradable polymeric nanoparticle is suitable for delivery in a subject by intravenous injection, further comprise an anti-cancer peptide that is CQCRRKN (therapeutic agent), wherein the PLA has an average molecular weight in the range of about 4,000 to about 90,000,g/mol and/or wherein the PEG-PPG-PEG has an average molecular weight in the range of about 4,000 g/mol to about 15,000 g/mol, wherein the diameter of the biodegradable polymeric nanoparticles is in the range of about 10 to about 200 nm, wherein the biodegradable polymeric nanoparticles are substantially free of emulsifier, wherein the therapeutic agent is encapsulated, surface conjugated, or adsorbed on the biodegradable polymeric nanoparticles, further comprising a targeting moiety selected from the group consisting of vitamins, small molecule drugs, ligands, amines, peptide fragments, antibodies, and aptamers.
‘904 claims are drawn to common subject matter that are not patentably distinct from Instant Claims. ‘904 claims are directed to a biodegradable polymeric nanoparticle formed of a block copolymer comprising poly(lactic acid) (PLA) chemically modified with a hydrophilic-hydrophobic block copolymer, wherein said hydrophilic-hydrophobic block copolymer is selected from PLA-PEG-PPG-PEG-PLA, wherein the PLA is chemically modified with a hydrophilic-hydrophobic block copolymer using a covalent bond, wherein the size of the biodegradable polymeric nanoparticle is in the range of about 30 to 120 nm, wherein the biodegradable polymeric nanoparticle is substantially free of emulsifier, wherein the average molecular weight of the PLA is less than or equal to about 16,000 g/mol, the average molecular weight of the PEG-PPG-PEG is in the range of about 4,000 g/mol to 15,000 g/mol, and wherein the composition is substantially free of emulsifier, wherein the therapeutic agent is encapsulated, surface conjugated, or adsorbed on the biodegradable polymeric nanoparticle, further comprise an anti-cancer peptide
‘904 claims differ from the Instant Claims in that the ‘904 claims do not recite the biodegradable polymeric nanoparticles are suitable for delivery in a subject by intravenous injection’.
However, Xiong cures the deficiency.
Xiong teaches poly(lactic acid) (PLA) were grafted to both ends of Pluronic F127 (PEO-PPO-PEO) to produce novel amphiphilic PLA-F127-PLA block copolymers (Abstract; Figure 1), where the structure is PLA-PEG-PPG-PEG-PLA (i.e., PLA-PEO-PPO-PEO-PLA) is a species of the claimed PLA-PEG-PPG-PEG-PLA, biodegradable polymeric nanoparticles, so that it would necessarily follow that the PLAF127-29 biodegradable polymeric nanoparticles as taught by Xiong are suitable for delivery by intravenous injection (teachings of Xiong are fully described above).
Accordingly, there is no unobvious distinction between the structural and functional characteristics of the claimed nanoparticles and the subject matter of the ‘904 Patent in view of Xiong.
Therefore, Instant Claims would have been prima facie obvious to one of skill in the art at the time the claimed invention was made in view of the ‘904 Patent and the teachings of Xiong, as a whole.
Claims 67, 69, 72-79 and 81 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6, 8, 14, 18 and 27 of copending Application No. 18145350 (herein ‘350) in view of Xiong et al (Synthesis and Aggregation Behavior of Pluronic F127/Poly(lactic acid) Block Copolymers in Aqueous Solutions, Macromolecules, p.9979, 2003, cited in IDS filed 1/06/2003).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant Claims are directed to a biodegradable polymeric nanoparticles comprising a PLA-PEG-PPG-PEG-PLA penta block copolymer, wherein the biodegradable polymeric nanoparticle is suitable for delivery in a subject by intravenous injection, further comprise an anti-cancer peptide that is CQCRRKN (therapeutic agent), wherein the PLA has an average molecular weight in the range of about 4,000 to about 90,000,g/mol and/or wherein the PEG-PPG-PEG has an average molecular weight in the range of about 4,000 g/mol to about 15,000 g/mol, wherein the diameter of the biodegradable polymeric nanoparticles is in the range of about 10 to about 200 nm, wherein the biodegradable polymeric nanoparticles are substantially free of emulsifier, wherein the therapeutic agent is encapsulated, surface conjugated, or adsorbed on the biodegradable polymeric nanoparticles, further comprising a targeting moiety selected from the group consisting of vitamins, small molecule drugs, ligands, amines, peptide fragments, antibodies, and aptamers.
‘350 claims are drawn to common subject matter that are not patentably distinct from Instant Claims. ‘350 claims are directed to a biodegradable polymeric nanoparticles comprising a PLA-PEG-PPG-PEG-PLA penta block copolymer, wherein one or both of the di-block copolymer and the penta-block copolymer comprise an average molecular weight of about 5,000 to 30,000 g/mol and/or wherein the polymeric nanoparticle has an average diameter of about 40-150 nm., wherein the biodegradable polymeric nanoparticles are substantially free of emulsifier, further comprise an anti-cancer peptide that is CQCRRKN (therapeutic agent), further comprising a targeting moiety selected from the group consisting of vitamins, small molecule drugs, ligands, amines, peptide fragments, antibodies, and aptamers.
‘350 claims differ from the Instant Claims in that the ‘350 claims do not recite the limitation herein the biodegradable polymeric nanoparticle is suitable for delivery in a subject by intravenous injection’.
However, Xiong cures the deficiency.
Xiong teaches poly(lactic acid) (PLA) were grafted to both ends of Pluronic F127 (PEO-PPO-PEO) to produce novel amphiphilic PLA-F127-PLA block copolymers (Abstract; Figure 1), where the structure is PLA-PEG-PPG-PEG-PLA (i.e., PLA-PEO-PPO-PEO-PLA) is a species of the claimed PLA-PEG-PPG-PEG-PLA, biodegradable polymeric nanoparticles, so that it would necessarily follow that the PLAF127-29 biodegradable polymeric nanoparticles as taught by Xiong are suitable for delivery by intravenous injection (teachings of Xiong are fully described above).
Accordingly, there is no unobvious distinction between the structural and functional characteristics of the claimed nanoparticles and the subject matter of the ‘350 claims in view of Xiong.
Therefore, Instant Claims would have been prima facie obvious to one of skill in the art at the time the claimed invention was made in view of the ‘350 claims and the teachings of Xiong, as a whole.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
Applicants argue that the '904 patent does not teach nanoparticles suitable for intravenous delivery, as the Examiner admits. Fetzer does not cure the deficiencies of the '904 patent. Fetzer does not teach PLA-PEG-PPG-PEG-PLA block co-polymers; instead, Fetzer appears to focus on polymers comprising PEG and/or PLGA.3 Fetzer only teaches a PLAPEG-PLA block co-polymer, an entirely different block co-polymer with a different structure than PLA-PEG-PPG-PEG-PLA, in prophetic Example 8 ofFetzer.4 Applicant notes that Example 8 of Fetzer is prophetic; therefore, Fetzer does not even show that the PLA-PEG-PLA block co-polymer could be made, let alone IV administered. Furthermore, there is no teaching in Fetzer that the PLAPEG-PLA co-polymer is IV administered, prophetic or otherwise.
Applicants’ arguments are moot in regards to Fetzer because the new ground of 35 U.S.C. 102(a)(1) rejection does not rely on the teachings of Fetzer in the rejections as set forth above.
Furthermore, ‘904 claims differ from the Instant Claims in that the ‘904 claims do not recite the biodegradable polymeric nanoparticles are suitable for delivery in a subject by intravenous injection’.
However, Xiong cures the deficiency.
Xiong teaches poly(lactic acid) (PLA) were grafted to both ends of Pluronic F127 (PEO-PPO-PEO) to produce novel amphiphilic PLA-F127-PLA block copolymers (Abstract; Figure 1), where the structure is PLA-PEG-PPG-PEG-PLA (i.e., PLA-PEO-PPO-PEO-PLA) is a species of the claimed PLA-PEG-PPG-PEG-PLA, biodegradable polymeric nanoparticles, so that it would necessarily follow that the PLAF127-29 biodegradable polymeric nanoparticles as taught by Xiong are suitable for delivery by intravenous injection (teachings of Xiong are fully described above).
Accordingly, there is no unobvious distinction between the structural and functional characteristics of the claimed nanoparticles and the subject matter of the ‘904 Patent in view of Xiong.
Therefore, Instant Claims would have been prima facie obvious to one of skill in the art at the time the claimed invention was made in view of the ‘904 Patent and the teachings of Xiong, as a whole.
Applicants argue that instant application has an earlier priority date than the '350 application. If this rejection is the only rejection remaining in this application, Applicant requests that the Examiner withdraw the rejection in this application and permit it to issue as a patent as provided in MPEP §804(I)(B)(l )(b )(i).
Applicants' arguments have been fully considered but they are not persuasive, because the statement in MPEP §804(I)(B)(l )(b )(i) doesn't apply at present because the provisional nonstatutory obviousness-type double patenting rejection is not the sole rejection. Furthermore, Applicants have distinctly and specifically pointed out supposed errors in the new Double Patenting rejections as set forth above.
Conclusions
No claim is allowed.
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/T.W./ Examiner, Art Unit 1619
/SARAH ALAWADI/ Primary Examiner, Art Unit 1619