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 .
Status of Claims
Receipt of Remarks/Amendments filed on 06/19/2026 is acknowledged. Claims 1-4 are amended and claims 5 and 8-10 are canceled. Claims 6-7 remain withdrawn as being drawn to a non-elected invention. Claims 1-4 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.
Withdrawn Objections/Rejections
Claim 1 was objected to because of an informality. Applicant’s amendment to the claim has overcome the objection and the objection is withdrawn.
Applicant’s cancellation of claims 5 and 8-10 has rendered the previous rejections of these claims moot and such rejections are withdrawn.
The following grounds of rejection are necessitated by amendment:
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 1-4 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 1 recites wherein “the polymer includes […] positively charged molecules” (plural) and then goes on to recite “R2 is a positively charged molecule” (singular). It is unclear if the polymer includes multiple positively charge molecules or just one positively charged molecule per polymer structure, or if different polymer structures with different positively charged molecules are used.
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.
Claim 2 recites “the molecular weight of the hydrophobic chain segment of the polymer and the hydrophobic chain segment of the targeting polymer is 1.5-5 times that of the hydrophilic chain segment of the polymer and the hydrophilic chain segment of the targeting polymer”. It is unclear if this means the total molecular weight of the hydrophobic chain segments from the polymer plus the targeting polymer is 1.5-5 times that of the total of the hydrophilic chain segments from the polymer plus the targeting polymer; OR if the hydrophobic chain segment of the polymer is 1.5-5 times that of its respective hydrophilic segment and the hydrophobic chain segment of the targeting polymer is 1.5-5 times that of its respective hydrophilic segment. For the sake of compact prosecution, the claim will be interpreted as the latter.
Claim 2 recites “the molecular weight of the positively charged molecule is 2%-40% of that of the hydrophilic chain segment of the polymer and the hydrophilic chain segment of the targeting polymer”. It is unclear if this means the molecular weight of the positively charged molecule is 2%-40% of that of the total of the hydrophilic chain segments from the polymer plus the targeting polymer; OR if the molecular weight of the positively charged molecule is 2%-40% of that of the hydrophilic chain segment of the polymer and separately 2%-40% of that of the hydrophilic chain segment of the targeting polymer. However, it is noted that the targeting polymer does not comprise any positively charged molecule. For the sake of compact prosecution, the claim will be interpreted as the molecular weight of the positively charged molecule is 2%-40% of that of the hydrophilic chain segment of the polymer.
Remaining claims 3 and 4 are rejected by virtue of their dependency on claims 1 and 2 and for failing to further clarify the issues above.
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 1-4 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 (on record), hereinafter NCBI.
Zhong discloses the preparation of a brain tumor treatment drug (abstract).
Regarding claim 1: 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, as discussed in detail below.
Formula I of Zhong reads on “the polymer”, which is illustrated by the first structure of claim 1:
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Formula I of Zhong has the following structure:
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(p. 2 of CN patent; labels added), 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, which also reads on the instantly claimed hydrophilic chain segment of the polymer. DTC and LA/TMC units are randomly copolymerized in Zhong to form a hydrophobic chain segment (p. 6, final para.). The 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. Overall, the hydrophobic chain segment of reads on a polycarbonate/polyester chain segment, depending on whether lactide (LA) or trimethylene cyclic carbonate (TMC) is used. 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, wherein R2 is a positively charged molecule.
Formulas II-III of Zhong read on the second structure of claim 1, 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 which also reads on the instantly claimed hydrophilic chain segment of the targeting polymer. DTC and LA/TMC units are randomly copolymerized in Zhong to form a hydrophobic chain segment (p. 6, final para.). 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. Overall, the hydrophobic chain segment reads on a polycarbonate/polyester chain segment, depending on whether lactide (LA) or trimethylene cyclic carbonate (TMC) is used. 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), which further read on the instantly claimed targeting polymer structure.
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.
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 of Zhong, 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) (p. 6, para. 2), with the lower limit of 2.5 falling within the instantly claimed range (i.e., 1.5-5). 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), with the lower limit of 20% falling within the instantly claimed range (i.e., 2%-40%). Specific examples of Zhong teach 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).
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 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 inhibits 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 claim 1, 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 1-4 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 claim 1, 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. The structures further reads on the first structure of the “polymer” in claim 1. 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 claim 1. 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 1-4 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 claim 1, 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. The structures further reads on the first structure of the “polymer” in claim 1. Since the above polymers are structurally identical to the polymer 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.
Response to Arguments
Applicant's arguments filed 06/19/2026 have been fully considered but they are not persuasive:
Applicant argues that the instantly claimed polymers of claim 1:
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, wherein R2 is a cyclic ester monomer, or a unit of a cyclic carbonate monomer after ring opening; are structurally different from the polymers of Zhong:
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Applicant argues that even if the polymers were formed in a one-pot polymerization method wherein PEG, LA/TMC, and DTC were mixed together in solution in Zhong, this method will not necessarily result in the polymer and targeting polymer of claim 1. Therefore, Applicant asserts that Zhong does not teach or suggest the polymer and the targeting polymer of claim 1.
Applicants argument that the polymerization method of Zhong which combines PEG, TMC, and DTC, for instance in Example 1 of Zhong (p. 8), would not necessarily result in the claimed polymer configurations is not convincing in view of Applicant’s instant specification. Example 1 of the instant specification (p. 11) teaches substantially the same method as Example 1 of Zhong. The instant specification provides the following reaction scheme for the combination of PEG, DTC, and TMC monomers:
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The resulting structure has the same configuration as the polymers of Zhong (i.e., DTC then TMC), rather than the configuration as claimed (i.e., TMC then DTC). As such, the methods of Zhong and the instant specification must result in a random polymerization of the hydrophobic chain monomers or the instant application possesses a 112(a) written description or enablement issue for not actually describing how or if the instantly claimed structures are achieved.
Additionally, the name of the polymer made in example 1 of the specification (PEG-P(TMC-DTC)) infers a different order than the structure shows (PEG-P(DTC-TMC)). As such, it appears that the order of the TMC and DTC monomers are arbitrary and random.
Other examples in the specification show different configurations depending on the cyclic ester or carbonate monomer used for R2 (i.e., TMC in Example 1). For example, the TMBPEC monomer results in the same configuration as Zhong (i.e., DTC first) ([0063]), while the CL and LA monomers result in the claimed configuration (i.e., DTC second) ([0062[; [0064]). Once again, either random polymerization of the hydrophobic chain monomers must be occurring or the instantly claimed structure is only described or enabled for specific cyclic ester/carbonate monomers.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNAH S ARMSTRONG whose telephone number is (571)272-0112. The examiner can normally be reached Mon-Fri 9-5 (Flex).
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/SUSANNAH S ARMSTRONG/Examiner, Art Unit 1616
/ERIN E HIRT/Primary Examiner, Art Unit 1616
Prosecution Insights