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
1. Applicant's election with traverse of compound 520:
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in the reply filed on 10/10/2025 is acknowledged. The traversal is on the ground(s) that a search for compound 520 would likely uncover art of interest to the other species having formula X. This is not found persuasive with respect to claim 172, because the searches performed for the elected compound did not render prior art relevant for the compounds set forth by the formula recited in claim 172. Thus, the requirement is still deemed proper with respect to claim 172 and is therefore made FINAL.
Since the searches performed for the elected compound rendered prior art relevant for the compounds set forth by the formulas recited in claims 30 and 36, the species election requirement between these species and the elected species is withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 4-28, 31-35, 37-58, 60-63, 65-72, 74-89, 91-104, 106-119, 121-167, 169-171, and 173-238 have been cancelled. Claims 29, 30, 36, 59, 64, 73, 90, 105, 120, 168, 172 have been amended. Claims 239-244 are new.
Claim 172 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-3, 29, 30, 36, 59, 64, 73, 90, 105, 120, 168, and 239-244 are under examination.
Claim Objections
2. Claims 1-3 are objected to because of the recitation that v and w are “1 to 25 kDa”. Since the variable v ana w indicate the number of repeats and not the molecular weight, correction to delete the recitation “kDa” is required.
3. Claim 30 is objected to because of the recitations “each RA is independently selected from” and “C1-10 alkyl C2-10 alkenyl,”. Correction to “RA is independently selected from” and “C1-10 alkyl, C2-10 alkenyl,” is required.
4. Applicant is advised that should claim 1 be found allowable, claim 2 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Double Patenting
5. 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.
6. Claims 1-3, 29, 30, 36, 59, 64, 73, 90, 105, 120, 168, and 239-244 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 9 of U.S. Patent No. 11,427,823, in view of Prieve et al. (WO 16/118697). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass the same nucleic acid conjugates comprising N-acetyl galactosamine (NAG) as a targeting ligand. The nucleic acid conjugate recited in the patent claim 1 is
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; the nucleic acid is an siRNA, which anticipates the genus of nucleic acids recited in the instant claims. This compound also anticipates the genus of compounds set forth by formulas X, I, and XXX recited in the instant claims 1-3, 30, 36, and 64; and also anticipates the genus of compounds encompassed by the formula recited in the instant claim 168.
The patent claims do not recite a membrane destabilizing polymer, nor do they recite a method. Prieve et al. teach that, since the delivery of siRNA conjugates is inefficient, large doses are needed for eliciting the desired biologic effect (see [4]). Prieve et al. teach using a membrane destabilizing polymer to enhance the delivery of siRNAs to the cell cytoplasm; the membrane destabilizing polymer comprises NAG as a ligand for targeted delivery to the liver. Prieve et al. teach using compositions comprising siRNAs and the membrane destabilizing polymer for delivering therapeutic siRNA to subjects. The membrane destabilizing polymer is a block copolymer having the structure:
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, where
NAG is:
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PEG12 is a linker of 12 ethylene glycol units, which could have the structure
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PEGMA is polyethyleneglycol methacrylate with 2-20 ethylene glycol units;
HMA is hexyl methacrylate (i.e., C6 alkyl-methacrylate);
D is DMAEMA (dimethylaminoethyl methacrylate);
P is PAA (propyl acrylic acid);
B is BMA (butyl methacrylate; i.e., a C4 alkyl-methacrylate);
m and n are each a mole fraction greater than 0, wherein m is greater than n and m + n = 1; q is a mole fraction of 0.2 to 0.75; r is a mole fraction of 0.05 to 0.6; s is a mole fraction of 0.2 to 0.75; q + r + s = 1; v is 1 to 25; w is 1 to 25 (see Abstract; [7]; [12]-[13]; [15]; [24]; [26]-[27]; [30]; [37]; [49]; [80]; [109]; [0168]; [0172], formula Vi on p. 59; [191]; [194]-[195]; [203]; [213]; [220]; [245]-[246]). Thus, the membrane destabilizing polymer of Prieve et al. is identical to the one recited in in the instant claims 1-3, 29, and 239-244).
Based on the teachings of Prieve et al., one of skill in the art would have reasonably concluded that the membrane destabilizing polymer would enhance the efficiency of the siRNA conjugate recited in the patent claims. One of skill in the art would have found obvious to modify the patent claims by adding the membrane destabilizing polymer of Prieve et al. with the reasonable expectation that doing so would enhance the activity of the siRNA conjugate. One of skill in the art would have also found obvious to deliver the resulting composition to a subject, when siRNA therapy was needed.
With respect to the instant claim 29, the second block of the copolymer of Prieve et al. is [DMAEMA-PAA BMA] and not
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(i.e., [DMAEMA-BMA-PAA]. However, the essential elements (i.e., DMAEMA, BMA, and PAA) are taught by the prior art. Moreover, Prieve et al. teach that DMAEMA, BMA, and PAA could be a randomly arranged within the block (see [17]-[18]; [67]). One of skill in the art would readily recognized that each of DMAEMA, BMA, and PAA performs its function regardless of the arrangement and would have found obvious to use routine experimentation and vary the arrangement, yielding no more than what have been expected from such an arrangement. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
Thus, the patent claims and the instant claims are obvious variants.
7. Claims 1-3, 29, 30, 36, 59, 64, 73, 90, 105, 120, 168, and 239-244 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, and 5 of U.S. Patent No. 12,043,843, in view of Prieve et al. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass the same nucleic acid conjugates comprising N-acetyl galactosamine (NAG) as a targeting ligand and the same method for delivering the conjugate to a subject. The compound recited in the patent claim 1 compound anticipates the genus of compounds set forth by formulas X, I, and XXX recited in the instant claims 1-3, 30, 36, and 64; and also anticipates the genus of compounds encompassed by the formula recited in the instant claim 168. The patent specification discloses that the compound could be in the stereoisomeric form recited in the instant claim 168 (see columns 71-72, last compound).
The patent claims do not recite a membrane destabilizing polymer, nor do they recite a method. Prieve et al. teach that, since the delivery of siRNA conjugates is inefficient, large doses are needed for eliciting the desired biologic effect (see [4]). Prieve et al. teach using a membrane destabilizing polymer to enhance the delivery of siRNAs to the cell cytoplasm; the membrane destabilizing polymer comprises NAG as a ligand for targeted delivery to the liver. Prieve et al. teach using compositions comprising siRNAs and the membrane destabilizing polymer for delivering therapeutic siRNA to subjects. The membrane destabilizing polymer is a block copolymer having the structure:
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, where
NAG is:
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PEG12 is a linker of 12 ethylene glycol units, which could have the structure
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83
384
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PEGMA is polyethyleneglycol methacrylate with 2-20 ethylene glycol units;
HMA is hexyl methacrylate (i.e., C6 alkyl-methacrylate);
D is DMAEMA (dimethylaminoethyl methacrylate);
P is PAA (propyl acrylic acid);
B is BMA (butyl methacrylate; i.e., a C4 alkyl-methacrylate);
m and n are each a mole fraction greater than 0, wherein m is greater than n and m + n = 1; q is a mole fraction of 0.2 to 0.75; r is a mole fraction of 0.05 to 0.6; s is a mole fraction of 0.2 to 0.75; q + r + s = 1; v is 1 to 25; w is 1 to 25 (see Abstract; [7]; [12]-[13]; [15]; [24]; [26]-[27]; [30]; [37]; [49]; [80]; [109]; [0168]; [0172], formula Vi on p. 59; [191]; [194]-[195]; [203]; [213]; [220]; [245]-[246]). Thus, the membrane destabilizing polymer of Prieve et al. is identical to the one recited in in the instant claims 1-3, 29, and 239-244).
Based on the teachings of Prieve et al., one of skill in the art would have reasonably concluded that the membrane destabilizing polymer would enhance the efficiency of the siRNA conjugate recited in the patent claims. One of skill in the art would have found obvious to modify the patent claims by adding the membrane destabilizing polymer of Prieve et al. with the reasonable expectation that doing so would enhance the activity of the siRNA conjugate. One of skill in the art would have also found obvious to deliver the resulting composition to a subject, when siRNA therapy was needed.
With respect to the instant claim 29, the second block of the copolymer of Prieve et al. is [DMAEMA-PAA BMA] and not
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(i.e., [DMAEMA-BMA-PAA]. However, the essential elements (i.e., DMAEMA, BMA, and PAA) are taught by the prior art. Moreover, Prieve et al. teach that DMAEMA, BMA, and PAA could be a randomly arranged within the block (see [17]-[18]; [67]). One of skill in the art would readily recognized that each of DMAEMA, BMA, and PAA performs its function regardless of the arrangement and would have found obvious to use routine experimentation and vary the arrangement, yielding no more than what have been expected from such an arrangement. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
Thus, the patent claims and the instant claims are obvious variants.
8. Claims 1-3, 29, 30, 36, 59, 64, 73, 90, 105, 120, 168, and 239-244 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-36 of copending Application No. 17/782,901 (reference application), in view of Prieve et al. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass the same siRNA-ligand conjugate and the same method for delivering the conjugate to a subject. The specific species of siRNA recited in the application claim 1 anticipate the genus of nucleic acids recited in the instant claim 1.
The application claims do not recite a membrane destabilizing polymer. Prieve et al. teach that, since the delivery of siRNA conjugates is inefficient, large doses are needed for eliciting the desired biologic effect (see [4]). Prieve et al. teach using a membrane destabilizing polymer to enhance the delivery of siRNAs to the cell cytoplasm; the membrane destabilizing polymer comprises NAG as a ligand for targeted delivery to the liver. Prieve et al. teach using compositions comprising siRNAs and the membrane destabilizing polymer for delivering therapeutic siRNA to subjects. The membrane destabilizing polymer is a block copolymer having the structure:
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, where
NAG is:
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96
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PEG12 is a linker of 12 ethylene glycol units, which could have the structure
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83
384
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PEGMA is polyethyleneglycol methacrylate with 2-20 ethylene glycol units;
HMA is hexyl methacrylate (i.e., C6 alkyl-methacrylate);
D is DMAEMA (dimethylaminoethyl methacrylate);
P is PAA (propyl acrylic acid);
B is BMA (butyl methacrylate; i.e., a C4 alkyl-methacrylate);
m and n are each a mole fraction greater than 0, wherein m is greater than n and m + n = 1; q is a mole fraction of 0.2 to 0.75; r is a mole fraction of 0.05 to 0.6; s is a mole fraction of 0.2 to 0.75; q + r + s = 1; v is 1 to 25; w is 1 to 25 (see Abstract; [7]; [12]-[13]; [15]; [24]; [26]-[27]; [30]; [37]; [49]; [80]; [109]; [0168]; [0172], formula Vi on p. 59; [191]; [194]-[195]; [203]; [213]; [220]; [245]-[246]). Thus, the membrane destabilizing polymer of Prieve et al. is identical to the one recited in in the instant claims 1-3, 29, and 239-244).
Based on the teachings of Prieve et al., one of skill in the art would have reasonably concluded that the membrane destabilizing polymer would enhance the efficiency of the siRNA conjugate recited in the patent claims. One of skill in the art would have found obvious to modify the application claims by adding the membrane destabilizing polymer of Prieve et al. with the reasonable expectation that doing so would enhance the activity of the siRNA conjugate. One of skill in the art would have also found obvious to deliver the resulting composition to a subject, when siRNA therapy was needed.
With respect to the instant claim 29, the second block of the copolymer of Prieve et al. is [DMAEMA-PAA BMA] and not
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(i.e., [DMAEMA-BMA-PAA]. However, the essential elements (i.e., DMAEMA, BMA, and PAA) are taught by the prior art. Moreover, Prieve et al. teach that DMAEMA, BMA, and PAA could be a randomly arranged within the block (see [17]-[18]; [67]). One of skill in the art would readily recognized that each of DMAEMA, BMA, and PAA performs its function regardless of the arrangement and would have found obvious to use routine experimentation and vary the arrangement, yielding no more than what have been expected from such an arrangement. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
Thus, the application claims and the instant claims are obvious variants.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
9. Claims 1-3, 29, 30, 36, 59, 64, 73, 90, 105, 120, 168, and 239-244 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 17/770,504 (reference application), in view of Prieve et al. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass the same siRNA-ligand conjugate and the same method for delivering the conjugate to a subject. The specific species of siRNA recited in the application claims anticipate the genus of nucleic acids recited in the instant claim 1.
The application claims do not recite a membrane destabilizing polymer. The patent claims do not recite a membrane destabilizing polymer, nor do they recite a method. Prieve et al. teach that, since the delivery of siRNA conjugates is inefficient, large doses are needed for eliciting the desired biologic effect (see [4]). Prieve et al. teach using a membrane destabilizing polymer to enhance the delivery of siRNAs to the cell cytoplasm; the membrane destabilizing polymer comprises NAG as a ligand for targeted delivery to the liver. Prieve et al. teach using compositions comprising siRNAs and the membrane destabilizing polymer for delivering therapeutic siRNA to subjects. The membrane destabilizing polymer is a block copolymer having the structure:
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, where
NAG is:
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72
96
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PEG12 is a linker of 12 ethylene glycol units, which could have the structure
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83
384
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PEGMA is polyethyleneglycol methacrylate with 2-20 ethylene glycol units;
HMA is hexyl methacrylate (i.e., C6 alkyl-methacrylate);
D is DMAEMA (dimethylaminoethyl methacrylate);
P is PAA (propyl acrylic acid);
B is BMA (butyl methacrylate; i.e., a C4 alkyl-methacrylate);
m and n are each a mole fraction greater than 0, wherein m is greater than n and m + n = 1; q is a mole fraction of 0.2 to 0.75; r is a mole fraction of 0.05 to 0.6; s is a mole fraction of 0.2 to 0.75; q + r + s = 1; v is 1 to 25; w is 1 to 25 (see Abstract; [7]; [12]-[13]; [15]; [24]; [26]-[27]; [30]; [37]; [49]; [80]; [109]; [0168]; [0172], formula Vi on p. 59; [191]; [194]-[195]; [203]; [213]; [220]; [245]-[246]). Thus, the membrane destabilizing polymer of Prieve et al. is identical to the one recited in in the instant claims 1-3, 29, and 239-244).
Based on the teachings of Prieve et al., one of skill in the art would have reasonably concluded that the membrane destabilizing polymer would enhance the efficiency of the siRNA conjugate recited in the patent claims. One of skill in the art would have found obvious to modify the patent claims by adding the membrane destabilizing polymer of Prieve et al. with the reasonable expectation that doing so would enhance the activity of the siRNA conjugate. One of skill in the art would have also found obvious to deliver the resulting composition to a subject, when siRNA therapy was needed.
With respect to the instant claim 29, the second block of the copolymer of Prieve et al. is [DMAEMA-PAA BMA] and not
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(i.e., [DMAEMA-BMA-PAA]. However, the essential elements (i.e., DMAEMA, BMA, and PAA) are taught by the prior art. Moreover, Prieve et al. teach that DMAEMA, BMA, and PAA could be a randomly arranged within the block (see [17]-[18]; [67]). One of skill in the art would readily recognized that each of DMAEMA, BMA, and PAA performs its function regardless of the arrangement and would have found obvious to use routine experimentation and vary the arrangement, yielding no more than what have been expected from such an arrangement. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
Thus, the application claims and the instant claims are obvious variants.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
10. Claims 1-3, 29, 30, 36, 59, 64, 73, 90, 105, 120, 168, and 239-244 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 197- 211 of copending Application No. 18/734,444 (reference application), in view of Prieve et al. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass the same siRNA-ligand conjugate and the same method for delivering the conjugate to a subject. The species of siRNA recited in the application claim 197 anticipates the genus of nucleic acids recited in the instant claim 1.
The application claims do not recite a membrane destabilizing polymer. The patent claims do not recite a membrane destabilizing polymer, nor do they recite a method. Prieve et al. teach that, since the delivery of siRNA conjugates is inefficient, large doses are needed for eliciting the desired biologic effect (see [4]). Prieve et al. teach using a membrane destabilizing polymer to enhance the delivery of siRNAs to the cell cytoplasm; the membrane destabilizing polymer comprises NAG as a ligand for targeted delivery to the liver. Prieve et al. teach using compositions comprising siRNAs and the membrane destabilizing polymer for delivering therapeutic siRNA to subjects. The membrane destabilizing polymer is a block copolymer having the structure:
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, where
NAG is:
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72
96
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PEG12 is a linker of 12 ethylene glycol units, which could have the structure
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83
384
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PEGMA is polyethyleneglycol methacrylate with 2-20 ethylene glycol units;
HMA is hexyl methacrylate; i.e., C6 alkyl-methacrylate;
D is DMAEMA (dimethylaminoethyl methacrylate);
P is PAA (propyl acrylic acid);
B is BMA (butyl methacrylate; i.e., a C4 alkyl-methacrylate);
m and n are each a mole fraction greater than 0, wherein m is greater than n and m + n = 1; q is a mole fraction of 0.2 to 0.75; r is a mole fraction of 0.05 to 0.6; s is a mole fraction of 0.2 to 0.75; q + r + s = 1; v is 1 to 25; w is 1 to 25 (see Abstract; [7]; [12]-[13]; [15]; [24]; [26]-[27]; [30]; [37]; [49]; [80]; [109]; [0168]; [0172], formula Vi on p. 59; [191]; [194]-[195]; [203]; [213]; [220]; [245]-[246]). Thus, the membrane destabilizing polymer of Prieve et al. is identical to the one recited in in the instant claims 1-3, 29, and 239-244).
Based on the teachings of Prieve et al., one of skill in the art would have reasonably concluded that the membrane destabilizing polymer would enhance the efficiency of the siRNA conjugate recited in the patent claims. One of skill in the art would have found obvious to modify the patent claims by adding the membrane destabilizing polymer of Prieve et al. with the reasonable expectation that doing so would enhance the activity of the siRNA conjugate. One of skill in the art would have also found obvious to deliver the resulting composition to a subject, when siRNA therapy was needed.
With respect to the instant claim 29, the second block of the copolymer of Prieve et al. is [DMAEMA-PAA BMA] and not
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(i.e., [DMAEMA-BMA-PAA]. However, the essential elements (i.e., DMAEMA, BMA, and PAA) are taught by the prior art. Moreover, Prieve et al. teach that DMAEMA, BMA, and PAA could be a randomly arranged within the block (see [17]-[18]; [67]). One of skill in the art would readily recognized that each of DMAEMA, BMA, and PAA performs its function regardless of the arrangement and would have found obvious to use routine experimentation and vary the arrangement, yielding no more than what have been expected from such an arrangement. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
Thus, the application claims and the instant claims are obvious variants.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112(d)
11. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
12. Claim 29 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
By reciting a polymer comprising
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, i.e., [DMAEMA-BMA-PAA], claim 29 fails to limit the subject matter of the parent claim 1, which is limited to a polymer comprising [DMAEMA-PAA-BMA].
It is noted that the specification teaches that the representation of the block within the brackets designates a polymer block with three monomer (a, b, and c); it does not designate a polymer block having one of each a, b, and c. Rather, it designates a polymer block where the monomers a, b, and c are randomly distributed throughout the block, where 35.9% by weight is monomer a; 51.5% by weight is monomer b; and 12.6% by weight is monomer c (see p. 9, line 10 through p. 10, line 12). However, claim 1 does not define that the distribution of monomers a, b, and c (i.e., DMAEMA-PAA-BMA) within the block is random; thus, claim 1 is reasonably interpreted as being drawn to a copolymer having the precise order DMAEMA-PAA-BMA shown in the brackets.
Furthermore, although not specifically defined by claim 29, the specification defines the values 75.5%; 24.5%; 35.9%; 51.5%; and 12.6% (corresponding to m, n, q, r, and s in claim 1) as representing represent weight %. However, m, n, q, r, and s are defined by claim 1 as being mole fractions. Mole fractions are not the same as weight %. For example, 35.9% DMAEMA, 51.5% BMA, and 12.6% PAA (i.e., q, r, and s in claim 1) correspond to the molar fractions 0.23, 0.36, and 0.17, respectively. This amounts to 0.76, which does not further limit claim 1, which requires that q + r+ s = 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Amending claim 1 to indicate that the distribution of DMAEMA, PAA, and BMA monomers within the block is random, together with a sufficient showing that the weight fractions recited in claim 29 further comply with the requirements in claim 1 that m + n =1 and q + r+ s = 1 would obviate the rejection.
Claim Rejections - 35 USC § 103
13. 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.
14. Claims 1-3, 29, 30, 36, 59, 64, 73, 90, 105, 120, 168, and 239-244 are rejected under 35 U.S.C. 103 as being unpatentable over Heyes et al. (WO 17/177326, published on 10/19/2017; cited on the IDS filed on 02/12/2024), in view of Prieve et al. (WO 16/118697).
Heyes et al. teach a method to deliver an oligonucleotide or siRNA to the liver in a subject, the method comprising delivering to the subject a conjugate set forth by formula I:
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106
192
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, where R1 is a targeting ligand; L1 and L2 are each absent or a linking group; R2 is a nucleic acid; Ring A is absent, a 3-20 membered cycloalkyl, a 5-20 membered aryl, a 5-20 membered heteroaryl, or a 3-20 membered heterocycloalkyl; RA is independently selected from the group consisting of hydrogen, hydroxy, CN, F, Cl, Br, I, -C1-2-alkyl-ORB, C1-10 alkyl, C2-10 alkenyl, and C2-10 alkynyl; wherein the C1-10 alkyl, C2-10 alkenyl, and C2-10 alkynyl are optionally substituted with one or more groups independently selected from halo, hydroxy, and C1-3 alkoxy; RB is hydrogen, a protecting group, a covalent bond to a solid support, or a bond to a linking group that is bound to a solid support; and n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, as encompassed by claims 1-3 and as recited in claim 30 (see Abstract; p. 1, line 23 through p. 2, line 13; p. 7, lines 8-11; p. 33, lines 4-6; claims 1, 2, 32, and 47).
In formula (I), R1 is:
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154
192
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, where
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194
932
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185
288
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and where T3-T6 are
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60
230
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(n = 1, 2, or 3), and B1-B3 are
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122
148
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(claims 64, 73, 90, 105, and 120) (see p. 48, line 18 through p. 49,
line 14).
The conjugate of formula (I) could be compound 231 where the saccharide targeting ligand is N-acetyl galactosamine (NAG):
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265
480
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i.e., same as elected compound 520 except that, in the linkers, n=3 (not 2) as in compound 520 (see p. 58). However, as per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, there is no evidence of record indicating that linkers where n=2 provides any unexpected properties as compared to linkers where n=3. Furthermore, Heyes et al. teach that linkers where n=2 could be used to obtain structurally similar conjugates (see conjugate 218 on p. 57). One of skill in the art would have found obvious to modify conjugate 231 by using linkers having n=2 with the reasonable expectation that doing so would result in a compound suitable to deliver oligonucleotides to the subject (claims 59, 64, and 168).
A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
In addition to the above, Heyes et al. teach delivering nucleic acid conjugates set by formula (XX):
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118
974
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where R1 is targeting ligand; L1 is absent or a linking group; L2 is absent or a linking group; R2 is a nucleic acid; B is
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72
96
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where the valence marked with * is attached to L1 or is attached to R1 if L1 is absent; and the valence marked with ** is attached to L2 or is attached to R2 if L2 is absent (claim 36) (see p. 47-48).
Heyes et al. do not teach co-delivering the membrane destabilizing polymer set forth by formula XX (claims 1-3). Prieve et al. teach using a membrane destabilizing polymer to enhance the delivery of LNPs encapsulating oligonucleotides (such as siRNAs) to the cell cytoplasm; the LNPs and the membrane destabilizing polymer both comprise a ligand targeting the cell of interest; the ligand is N-acetyl galactosamine (NAG) for targeted delivery to the liver. Prieve et al. teach using compositions comprising siRNAs and the membrane destabilizing polymer for delivering therapeutic siRNA to subjects. The membrane destabilizing polymer is a block copolymer having the structure:
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41
384
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, where
NAG is:
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72
96
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PEG12 is a linker of 12 ethylene glycol units, which could have the structure
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83
384
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PEGMA is polyethyleneglycol methacrylate with 2-20 ethylene glycol units;
HMA is hexyl methacrylate (i.e., C6 alkyl-methacrylate);
D is DMAEMA (dimethylaminoethyl methacrylate);
P is PAA (propyl acrylic acid);
B is BMA (butyl methacrylate; i.e., a C4 alkyl-methacrylate);
m and n are each a mole fraction greater than 0, wherein m is greater than n and m + n = 1; q is a mole fraction of 0.2 to 0.75; r is a mole fraction of 0.05 to 0.6; s is a mole fraction of 0.2 to 0.75; q + r + s = 1; v is 1 to 25; w is 1 to 25 (see Abstract; [7]; [12]-[13]; [15]; [24]; [26]-[27]; [30]; [37]; [49]; [80]; [109]; [0168]; [0172], formula Vi on p. 59; [191]; [194]-[195]; [203]; [213]; [220]; [245]-[246]). Thus, the membrane destabilizing polymer of Prieve et al. is identical to the one recited in claims 1-3 and 239-244.
Although Prieve et al. do not specifically teach using the membrane destabilizing polymer in conjunction with siRNA conjugates, Prieve et al. do teach that the delivery of siRNA conjugates is inefficient and that large doses are needed for eliciting the desired biologic effect (see [4]).
Based on the teachings in Prieve et al., one of skill in the art would have reasonably concluded that the membrane destabilizing polymer would also enhance the efficiency of the siRNA conjugates, including the conjugate taught by Heyes et al. One of skill in the art would have found obvious to modify the method of Heyes et al. by administering the conjugate together with the membrane destabilizing polymer of Prieve et al., with the reasonable expectation that doing so would enhance the activity of the siRNA.
With respect to claim 29, Prieve et al. teach [DMAEMA-PAA BMA] as the second block and not:
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(i.e., [DMAEMA-BMA-PAA]. However, there is no evidence on the record that the claimed arrangement result in an unexpected property. The arrangement is not significant if it does not provide a novel feature. The essential elements (i.e., DMAEMA, BMA, and PAA) are taught by Prieve et al. Moreover, Prieve et al. teach that DMAEMA, BMA, and PAA could be randomly arranged within the second block (see [17]-[18]; [67]). One of skill in the art would readily recognized that each of DMAEMA, BMA, and PAA performs its function regardless of the arrangement and would have found obvious to use routine experimentation and vary the arrangement, yielding no more than what would have been expected from such an arrangement. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
15. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633