DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-5 and 8-10, in the reply filed on 01/13/2026 is acknowledged.
Accordingly, claims 6-7 are withdrawn as being directed to a non-elected invention. Additionally, since Group I, drawn to an anti-tumor nano adjuvant, was elected, the use claims which were presented in several groups are being treated as product claims rather than their alternative methods. Claims 1-5 and 8-10 are examined on the merits herein.
Priority
The instant application filed 12/21/2022, is a 371 filing of PCT/CN2021/074571, filed 01/31/2021, which claims foreign priority to CN202010167801.2, filed 03/11/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/21/2022 and 02/15/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informality: The term “polyca rbonate”, which appears to be a typographical error.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
1. Claims 1-5 and 8-10 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.
Claims 1 and 10 recite in the final two lines that “the hydrophobic chain segment is a polycarbonate chain segment and/or a polyester chain segment”. It is unclear if this limitation is in reference to the hydrophobic chain segment of the polymer or the targeting polymer since both comprise a hydrophobic chain segment. The claim does not define if these hydrophobic chain segments are the same or different in the polymer versus the targeting polymer.
Claim 2 recites “the hydrophilic chain segment” and “the hydrophobic chain segment”. Once again it is unclear if these limitations refer to the chain segments of the polymer or the targeting polymer or if these segments are the same for both. For the sake of compact prosecution, the limitations will be met if it is true for either the polymer or the targeting polymer.
Claim 2 recites wherein “the positively charged molecules [plural] include spermine and polyethyleneimine” and then goes onto recite “the molecular weight of the positively charged molecule [singular] is […]”. Thus, it is unclear if the molecular weight limitation refers to both spermine and polyethyleneimine or only one of the two. For the sake of compact prosecution, the molecular weight limitation will be met if either spermine or PEI have a molecular weight within the instantly claimed range.
Claims 8-10 recite the use of an anti-tumor nano adjuvant and the use of a vesicle formed by a reversibly cross-linked biodegradable polymer without setting forth any steps. Therefore, it is unclear if the claim is drawn to the product itself or a process of using said product. For the purposes of examination, the instant claims 8-10 will be interpreted as being directed to a product since the claims fail to define any positively recited, active steps that would properly define a process claim within the meaning of 35 U.S.C. §101, and the recited limitations directed to the “use” of the product will be interpreted as an intended use of the composition per se.
Claim 10 recites a “[u]se of the vesicle formed by a reversibly cross-linked biodegradable polymer”. Claim 10 is an independent claim as currently written meaning there is no antecedent basis for any recitation of “the vesicle” since nowhere in claim 10 recites “a vesicle” to begin with.
Any remaining claims are rejected by virtue of their dependency to rejected claim 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 8-10 are rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See, for example, Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F.Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Claims 8-10 recites the use of an anti-tumor nano adjuvant and a vesicle formed by a reversibly cross-linked biodegradable polymer without setting forth any steps. Therefore, claims 8-10 are neither product claims nor proper process claims. As such, claims 8-10 do not fall under any statutory subject matter, and are rejected. "Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. 101"). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967), the Board held the following claim to be an improper definition of a process: "The use of a high carbon austenitic iron alloy having a proportion of free carbon as a vehicle brake part subject to stress by sliding friction." In Clinical Products Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966), the district court held the following claim was definite, but that it was not a proper process claim under 35 U.S.C. 101: "The use of a sustained release therapeutic agent in the body of ephedrine absorbed upon polystyrene sulfonic acid." Additionally, although a claim should be interpreted in light of the specification disclosure, it is generally considered improper to read limitations contained in the specification into the claims. See In re Prater, 415 F.2d 1393, 162 USPQ 541 (CCPA 1969) and In re Winkhaus, 527 F.2d 637, 188 USPQ 129 (CCPA 1975), which discuss the premise that one cannot rely on the specification to impart limitations to the claim that are not recited in the claim. See MPEP 2173.05.
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.
1. Claims 1-5 and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong, Z., et al. (CN 107998082 B, 05/08/2018, CN patent and ip.com translation on record), hereinafter Zhong in view of Alizadeh D, et al. (2010). Induction of anti-glioma natural killer cell response following multiple low-dose intracerebral CpG therapy. Clin Cancer Res. 16(13):3399-408, (on record), hereinafter Alizadeh as evidenced by the National Center for Biotechnology Information (2026). PubChem Compound Summary for CID 1103, Spermine (PTO-892), hereinafter NCBI.
Zhong discloses the preparation of a brain tumor treatment drug (abstract).
Regarding claims 1 and 10: A polymer vesicle nano-drug is obtained by loading a drug into a reversible cross-linked biodegradable polymer vesicle; the reversible crosslinked biodegradable polymer vesicle is obtained by self-assembling and then crosslinking. The polymer is a polymer of formula I, or the polymer is a mixture of the polymer of the formula I, the polymer of the formula II, and the polymer of the formula III (p. 3, para. 3). Formula I reads on the instantly claimed polymer while formulas II and III read on the instantly claimed targeting polymer. The polymers of formulas I-III have the following structure:
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(p. 2 of CN patent; labels added).
In the polymer of formula I, formula II, or formula III, DTC and LA/TMC units are randomly copolymerized to form a hydrophobic chain segment (p. 6, final para.). One end of the hydrophobic part is connected with hydrophilic PEG (p. 6, final para.), which reads on the hydrophilic chain segment.
R4 is one of the following structural formulas:
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(p. 2 of CN patent), with the first option being derived from PEI and the second being derived from spermine (p. 3, para. 5), both of which read on the positively charged molecules. A targeting molecule at the PEG end may be coupled to obtain a targeting polymer (i.e., R1 or R5 of formula II-III) (p. 3, para. 6; p. 6, R group definitions). Such a targeting polymer also comprises the hydrophilic and hydrophobic chain segments discussed above. R3 is one of the following structural formulas:
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(p. 2 of CN patent), with the first option being derived from TMC (i.e., trimethylene cyclic carbonate), and the second being derived from LA (i.e., lactide). Depending on the selected monomer, the hydrophobic chain segment will be a polyester or polycarbonate chain segment. Given that the vesicle of Zhong has the same structural units and assembly as that which is instantly claimed, it will necessarily possess an asymmetric membrane structure. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594).
Regarding claim 2: As discussed above, the hydrophilic chain segment of formulas I-III is PEG (i.e., polyethylene glycol). The hydrophobic chain segment is derived partially from DTC (p. 6, final para.; p. 8-9, Examples). Based on the figures above and the instant specification, it appears that the DTC unit of Zhong, is obtained by ring opening of a cyclic carbonate monomer containing a disulfide five-membered cyclic functional group ([0011] of instant specification). Also discussed above, PEI (i.e., polyethyleneimine) and spermine are used to modify the tail end of the polymer chain (p. 3, para. 5; p. 7, para. 7-8), both of which read on the positively charged molecules. In the polymers of formula I-III, the total molecular weight of the hydrophobic chain segment is 2.5-10 times of the molecular weight of the PEG chain segment (i.e., the hydrophilic chain segment) and the molecular weight of PEI (i.e., a positively charged molecule) is 20%-55% of the molecular weight of the PEG chain segment (p. 6, para. 2). Specific examples teaches the synthesis of block copolymers PEG5k-P(DTC2k-TMC15k)-bPEI1.8k (p. 8, Example 1) and PEG5k-P(TMC15k-DTC2k)-Sp (p. 9, Example 3). In both of these examples the hydrophobic chain segment totals to a molecular weight of 17kDa, which is 3.4 times that of the hydrophilic 5kDa PEG segment. The molecular weight of the PEI in example 1 is 1.8kDa which is 36% of the 5kDa molecular weight PEG, thereby reading on the instantly claimed range of 2-40%. The spermine in example 3 has a molecular weight of 202 g/mol (i.e., Da), as evidenced by NCBI. Such a molecular weight is 4% of the 5kDa molecular weight PEG which also reads on the instantly claimed range of 2-40%. It is noted that when PEI or Spermine is modified at the tail end of a polymer chain, the efficiency of entrapping macromolecular drugs by the vesicles can be greatly improved through electrostatic interaction and hydrogen bond action (p. 7, para. 7).
Regarding claim 3: In the polymers of formula I-III, the molecular weight of the PEG chain segment is 2000-10000 Da (p. 6, para. 2). Specific example teaches the synthesis of block copolymers PEG5k-P(DTC2k-TMC15k)-bPEI1.8k (p. 8, Example 1) and PEG5k-P(TMC15k-DTC2k)-Sp (p. 9, Example 3). In both examples the molecular weight of the PEG is 5kDa, which reads on the instantly claimed molecular weight (i.e., 5-7.5 kDa). The molecular weight of the PEI in example 1 is 1.8 kDa, which is 36% of the 5kDa molecular weight PEG, thereby reading on the instantly claimed range of 7-40%. The spermine in example 3 has a molecular weight of 202 g/mol (i.e., Da), as evidenced by NCBI. Such a molecular weight is 4% of the 5kDa molecular weight PEG which reads on the instantly claimed range of 2.7-4%.
Regarding claim 4: The medicine is a small molecule medicine, a large molecule protein medicine or a gene medicine, the targeting molecule is ANG, ApoE or iNGR, preferably, the first targeting molecule is ApoE (p. 6, 2nd to last paragraph). Example 2 teaches a diblock polymer comprising ApoE polypeptide as the targeting molecule (p. 9, Example 1).
Regarding claim 5: As discussed above, formula I of Zhong reads on “the polymer”, which is illustrated by the first structure of claim 5:
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Formula I of Zhong has the following structure:
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, wherein the unit comprising R3 is derived from LA or TMC and R4 is an amide-PEI or amide-spermine structure (p. 2 of CN patent; p. 8-9; Examples 1 and 3). Working from left to right of the instantly claimed structure of “the polymer”, the above structure of Zhong teaches an OMe end group which reads on instantly claimed R1. The above structure of Zhong comprises a PEG unit as shown in the instantly claimed structure. The hydrophobic segment of Zhong comprises units derived from LA or TMC. LA (lactide) and TMC (trimethylene cyclic carbonate) units are derived from cyclic ester/carbonate monomers after ring opening as evidenced by the instant specification ([0048] of instant spec.), therefore reading on instantly claimed R2. The DTC unit of the hydrophobic segment of Zhong has the same structure as the cyclic disulfide unit as shown in the instantly claimed structure. The R4 group of Zhong has the following structure:
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(p. 2 of CN patent; p. 8-9, Examples 1 and 3), both of which read on the instantly claimed amide-R2 end group.
Formulas II-III of Zhong read on the second structure of claim 5, defined as the “targeting polymer”:
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Formulas II-III of Zhong have the following structure:
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Working from left to right of the instantly claimed structure of the “targeting polymer”, Zhong teaches wherein the R1 and R5 groups are targeting molecules (p. 6, R group definitions; p. 9; Example 2), which reads on the instantly claimed R group. As seen in the structures above, the R2 group of Zhong links the targeting molecule to the rest of the polymer, therefore reading on the instantly claimed linkage group of R1. The above structures of Zhong comprise a PEG unit as shown in the instantly claimed structure. The hydrophobic segment of Zhong comprises units derived from LA or TMC. LA (lactide) and TMC (trimethylene cyclic carbonate) units are derived from cyclic ester/carbonate monomers after ring opening as evidenced by the instant specification ([0048] of instant spec.), therefore reading on instantly claimed R2. The DTC unit of the hydrophobic segment of Zhong has the same structure as the cyclic disulfide unit as shown in the instantly claimed structure. When the polymer is a targeting polymer the R4 end group of Zhong is a hydrogen (p. 6, R group definitions; p. 9, Example 2).
It is noted that the hydrophobic chain segments of Zhong are illustrated as having the DTC units first and the LA/TMC units second (moving left to right), while the instantly claimed structures show the opposite. However, looking at the synthesis methods of the instant specification (p. 11-12, Examples 1 and 2) and Zhong (p. 8-9, Examples 1-2) it appears that the polymers are formed in a one-pot polymerization method wherein PEG, LA/TMC, and DTC are mixed together in solution. Zhong explicitly teaches wherein the DTC and LA/TMC units are randomly copolymerized to form a hydrophobic chain segment (p. 6, final para.). Thus, the LA/TMC and DTC units will exist in a random order within the hydrophobic chain segment, thereby reading on the instantly claimed structure.
Regarding claims 8-9: Zhong discloses the polymer vesicle nano-drug in the preparation of a brain tumor treatment drug, thereby reading on the use of the instantly claimed vesicle in preparing an anti-tumor drug, specifically an anti-brain tumor drug. It is noted, however, that there is no requirement for Zhong to teach such a use since the instant claims define the same structure provided for in instant claim 1 and its intended use. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention (i.e., the vesicle structure of claim 1), and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)
The teachings of Zhong differ from that of the instantly claimed invention in that Zhong does not explicitly teach wherein the loaded drug is an oligonucleotide that can activate an immune response, as recited in claims 1 and 10, and further defined in claim 4, nor does Zhong explicitly define a vesicle wherein the positively charged molecules include both spermine and polyethyleneimine, as recited in claim 2.
Alizadeh discloses that CpG oligodeoxynucleotides (CpG-ODNs) are currently being tested as single agents, vaccine adjuvants, or in combination with other therapies in patients with various cancers. The efficacy of CpG-ODN immunotherapy has also been studied in brain tumors. Initial reports by Carpentier et al. demonstrated an 88% cure rate in rats bearing intracranial CNS-1 gliomas after multiple direct intratumoral CpG-ODN injections (discussion, para. 1). The stimulation of toll-like receptor-9 (TLR9) by CpG oligodeoxynucleotides (CpG-ODN) counteracts the immunosuppressive microenvironment and to inhibit tumor growth in glioma models (abstract; purpose). Alizadeh demonstrates that two and four intracranial injections of low-dose CpG-ODN eradicated gliomas in 70% of mice. Moreover, surviving animals exhibited durable tumor free remission (> 3 months), and were protected from intracranial rechallenge with GL21 gliomas, demonstrating the capacity for long-term anti-tumor immunity (abstract; results). The exact anti-tumor mechanism of CpG-ODN is not clear but most likely due to both tumor cell apoptosis and immune activation (discussion, para. 2). The CpG-ODNs of Alizadeh reads on an oligonucleotide drug that can activate an immune response as recited in claims 1 and 10, specifically the CpG of claim 4.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to load the CpG-ODNs of Alizadeh on the vesicle of Zhong since CpG-ODNs are known and effective drugs for inhibiting tumor growth in glioma models (i.e., brain tumors). One of ordinary skill in the art would have been motivated to load the CpG-ODNs of Alizadeh in the vesicles of Zhong since Zhong teaches nano-drugs for treating brain tumors and Alizadeh teaches that
CpG-ODNs are successful in eradicating gliomas (i.e., brain tumors in mice). One of ordinary skill in the art could have substituted out the brain tumor treatment drug of Zhong for the known CpG-ODNs of Alizadeh to predictably yield the instant invention. Alternatively, one of ordinary skill in the art could have added the CpG-ODNs of Alizadeh in addition to the drug of Zhong to generate a dual therapeutic used to treat brain tumors. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
It would have been further prima facie obvious to one of ordinary skill in the art to generate a vesicle comprising polymers with a mixture of spermine and PEI end groups since both are known and routine in the art as taught by different embodiments of Zhong. One of ordinary skill in the art would have been motivated to provide a vesicle with polymers having a mixture of spermine and PEI end groups since PEI and spermine modified polymer chains increase the efficiency of entrapping macromolecular drugs as taught by Zhong. One of ordinary skill in the art could have combined polymers having a mixture of positively charged end groups (i.e., spermine and PEI) according to the know polymerization and crosslinking methods of Zhong to predictably generate the instantly claimed vesicle.
One of ordinary skill in the art would have had a reasonable expectation of success in making the above modifications since Zhong and Alizadeh both teach therapeutic agents for treating brain tumors, and Zhong teaches wherein the drug may be a macromolecule which encompasses oligonucleotides such as the CpG of Alizadeh. Furthermore, Zhong teaches all of the methods needed for one of ordinary skill in the art to combine different polymer chains such as those comprising PEI or spermine.
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 1-5 and 8-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,478,586 in view of Alizadeh. The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims and would have been obvious over the reference claims in view of Alizadeh.
Conflicting claim 1 recites a drug-loaded polymer vesicle, wherein the drug-loaded polymer vesicle is prepared from a small molecule drug and an amphiphilic block polymer; or from the small molecule drug, the amphiphilic block polymer, a functionalized polyethylene glycol (PEG) polymer, and a targeting molecule; wherein the chemical structural of the amphiphilic block polymer is one of the following formulas:
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. Such polymers read on the polymer of instant claims 1 and 10, comprising a hydrophilic chain segment (i.e., the leftmost PEG unit above), a hydrophobic chain segment (i.e., the central segment within the brackets above), and positively charged molecules (i.e., the NH and NH2 containing segment above). The hydrophobic segment above also comprises a polycarbonate chain as instantly claimed. Since the above polymers are structurally identical to the polymers defined in instant claim 1, they may also be defined as reversibly cross-linked biodegradable polymers. The vesicle of the conflicting claims therefore reads on the instantly claimed vesicle comprising an asymmetric structure which is necessarily obtained by the self-assembly of the above polymer. The conflicting claims differ from the instant claims in that the conflicting claims do not teach the drug to be an oligonucleotide. Alizadeh discloses that CpG oligodeoxynucleotides (CpG-ODNs) are currently being tested as single agents, vaccine adjuvants, or in combination with other therapies in patients with various cancers. The efficacy of CpG-ODN immunotherapy has also been studied in brain tumors. Initial reports by Carpentier et al. demonstrated an 88% cure rate in rats bearing intracranial CNS-1 gliomas after multiple direct intratumoral CpG-ODN injections (discussion, para. 1). The stimulation of toll-like receptor-9 (TLR9) by CpG oligodeoxynucleotides (CpG-ODN) counteracts the immunosuppressive microenvironment and to inhibit tumor growth in glioma models (abstract; purpose). The CpG-ODNs of Alizadeh reads on an oligonucleotide drug that can activate an immune response as recited in claims 1 and 10. It would have been prima facie obvious to one of ordinary skill in the art to load the CpG-ODNs of Alizadeh on the conflicting vesicle since CpG-ODNs are known and effective drugs for inhibiting tumor growth. One of ordinary skill in the art could have combined the CpG ODNs of Alizadeh with the conflicting vesicle according to known methods to predictably yield the instantly claimed invention.
Claims 1-5 and 8-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/012,611 in view of Alizadeh. The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims and would have been obvious over the reference claims in view of Alizadeh.
Copending claim 1 recites a peptide targeting drug-load polymer vesicle having an asymmetric structure, which is obtained by co- loading an amphiphilic triblock polymer and a functionalized amphiphilic block polymer with a small molecule drugs and then followed by a peptide preparation; the chemical structural formula of the amphiphilic triblock polymer is as follows:
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. Such polymers read on the polymer of instant claims 1 and 10, comprising a hydrophilic chain segment (i.e., the leftmost PEG unit above), a hydrophobic chain segment (i.e., the central segment within the brackets above), and positively charged molecules (i.e., the NH and NH2 containing segment above). The hydrophobic segment above also comprises a polycarbonate chain as instantly claimed. Since the above polymers are structurally identical to the polymers defined in instant claim 1, they may also be defined as reversibly cross-linked biodegradable polymers. The vesicle of the copending claims therefore reads on the instantly claimed vesicle comprising an asymmetric structure which is necessarily obtained by the self-assembly of the above polymer. The copending claims differ from the instant claims in that the copending claims do not teach the drug to be an oligonucleotide. Alizadeh discloses that CpG oligodeoxynucleotides (CpG-ODNs) are currently being tested as single agents, vaccine adjuvants, or in combination with other therapies in patients with various cancers. The efficacy of CpG-ODN immunotherapy has also been studied in brain tumors. Initial reports by Carpentier et al. demonstrated an 88% cure rate in rats bearing intracranial CNS-1 gliomas after multiple direct intratumoral CpG-ODN injections (discussion, para. 1). The stimulation of toll-like receptor-9 (TLR9) by CpG oligodeoxynucleotides (CpG-ODN) counteracts the immunosuppressive microenvironment and to inhibit tumor growth in glioma models (abstract; purpose). The CpG-ODNs of Alizadeh reads on an oligonucleotide drug that can activate an immune response as recited in claims 1 and 10. It would have been prima facie obvious to one of ordinary skill in the art to load the CpG-ODNs of Alizadeh on the copending vesicle since CpG-ODNs are known and effective drugs for inhibiting tumor growth. One of ordinary skill in the art could have combined the CpG ODNs of Alizadeh with the copending vesicle according to known methods to predictably yield the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNAH S ARMSTRONG whose telephone number is (571)272-0112. The examiner can normally be reached Mon-Fri 7:30-5 (Flex).
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/SUSANNAH S ARMSTRONG/Examiner, Art Unit 1616
/ERIN E HIRT/Primary Examiner, Art Unit 1616