Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment to the claims filed after non-final office action on July 17, 2026 is acknowledged. Claims 2, 5, 11 were amended, claims 1, 3, 12, 18-20 are canceled and claims 2, 4-11, 13-17 are pending in the instant application. The restriction was deemed proper and made final previous office action.
The restriction requirement was deemed proper and made FINAL in a previous office action.
Claims 2, 4-11, 13-17 are examined on the merits of this office action.
Withdrawn Rejections/Objections
The rejection of claims 2, 4-11, 13-17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11642419 B2 in view of Dasseux (US20030203842 A1) is withdrawn in view of the filing and approval of the terminal disclaimer on July 17, 2026.
The rejection of claims 2, 4, 7-11, 13 and 16-17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11833196 B2 in view of Sparks (US6514523, cited in IDS) and Dasseux (US20030203842 A1) is withdrawn in view of the filing and approval of the terminal disclaimer on July 17, 2026.
The rejection of claims 2, 4, 7-11, 13, 16-17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of US Patent No. 12257352 in view of Sparks (US6514523, cited previously) in view of Dasseux (US20030203842 A1) is withdrawn in view of the filing and approval of the terminal disclaimer on July 17, 2026.
The rejection of claims 2, 4, 7-11, 13 and 16-17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11219673B2 B2 in view of Sparks (US6514523, cited in IDS) and Dasseux (US20030203842 A1) is withdrawn in view of the filing and approval of the terminal disclaimer on July 17, 2026.
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The rejection of claims 2, 4, 7-11, 13 and 16-17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12324843 in view of Sparks (US6514523, cited in IDS) and Dasseux (US20030203842 A1) is withdrawn in view of the filing and approval of the terminal disclaimer on July 17, 2026.
The rejection of claims 2, 4-11, 13-17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of amendment of the claim filed on July 17, 2026.
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Terminal Disclaimer
The terminal disclaimer filed on Julu 17, 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11642419, 12324843, 11219673, 12257352, 11833196 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Maintained/Revised Rejections
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 2, 4, 7-11, 13, 16-17 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 58, 85, 89 of Co-pending 17/628418 in view of Sparks (US6514523, cited previously) and Dasseux (US20030203842 A1).
The instant application claims “A composition comprising a synthetic high density lipoprotein_(HDL) - therapeutic agent (sHDL-TA) nanoparticle, wherein the sHDL comprises at least one therapeutic agent, at least one HDL apolipoprotein, and at least one phospholipid wherein the therapeutic agent is between 0.01 - 20% by weight of the sHDL-TA, and the sHDL is between 80-99.99% by weight of the sHDL-TA, and wherein the HDL apolipoprotein is an apolipoprotein A-I (apo A-I) mimetic having a sequence selected from the group consisting of: PPVLDWFRELLNELLEALKQKLK (SEQ ID NO: 35), PVLDLFRELLNEWLEALKQKLK (SEQ ID NO: 54), and PVLDEFRELLNELLEALKQKLK (SEQ ID NO: 79). The instant application further claims wherein the mimetic is one of SEQ ID Nos: 35, 54, 79; wherein the lipid is PC or DMPC (Claim 4); wherein the therapeutic is an anticoagulant, beta blocker, statin, Liver X R agonist (see claims 5-6, 14-15); further comprising an imaging agent (claims 9, 11, 17); 20% therapeutic, 80-99% sHDL (see claim 10); 6-20 nm particle size (see claim 7).
Co-pending 17/628418 claims a composition comprising an sHDL nanoparticle associated with a plurality of tolerogenic antigens in such a manner that the resulting composition is capable of facilitating strong immune tolerance to antigens associated with an autoimmune disease upon administration to a subject, wherein the sHDL nanoparticle comprises a mixture of at least one phospholipid and at least one HDL apolipoprotein or apolipoprotein mimetic (claim 1); and wherein the Apo A-I is SEQ ID NO:4 which is identical to instant SEQ ID NO:4 (claim 1). Co-pending Application 17/628418 further claims inclusion of an antigen to facilitate immune tolerance which meets the limitations of a therapeutic (see claims 1 and 6)
Co-pending Application 17/628418 doesn’t specifically claim (i) the concentrations of the therapeutic in the composition, (ii) inclusion of an imaging agent and (iii) and instant SEQ ID NO:35 as the mimetic peptide.
However, Sparks teaches a composition comprising a synthetic HDL, wherein the synthetic HDL comprises Apo AI and a phospholipid (see abstract). Sparks teaches wherein the therapeutic agent is in the range of 1-20% (see column 6, lines 39-40) and provide an example of 20% drug and 80% sHDL (see Example 1) meeting the limitations of claim 117. Sparks teaches wherein the size of the particle is 5-20 nm (see abstract) and in particular 7.5 nm as a preferred diameter (see column 7, lines 14-16). Sparks discloses wherein the sHDL-therapeutic agent further comprises an imaging agent (Carbon-14) which meets the limitation of nuclear imaging agent.
However, Dasseux teaches ApoA-I agonist peptides that are designed to mimic the structure and biological activity of native apoA-I (see Abstract, paragraphs 0001-0002). Dasseux teaches that the disclosed ApoA-I agonist peptides form amphipathic alpha helices in the presence of lipids (see paragraph 0001, 0084, 088); bind phospholipids and form HDL-like or pre-B-HDL like complexes (see paragraphs 0014, 0042, 0044, 0084); associate with the HDL component in plasma and increase HDL and pre-BHDL particles (see paragraphs 0084-0086). Dasseux expressly discloses ApoA-I mimetic peptide sequences SEQ ID Nos:35, 54, 79, which are identical to the sequences recited in claims 2 and 11 (see claim 19; paragraph 0019; claims 19 and 42). Dasseux further teaches that these ApoAI agonist peptides are formulated as peptide lipid complexes, including phospholipid complexes that are suitable for parenteral administration and form HDL-like particles (see paragraphs 0042-0046, 0081-0083, 0397-0402, see also Figure 11).
It would have been obvious to optimize the amount of therapeutic in the particle to achieve optimal therapeutic efficacy. Furthermore, it would have been obvious before the invention to add an imaging agent to the sHDL nanoparticle of Co-pending Application 17/628418 to visualize intracellular delivery of the particle to determine effectiveness of the particle. There is a reasonable expectation of success given that imaging labels including radionuclides are commonly used to track the delivery of the sHDL.
Regarding instant SEQ ID NO:35 as the ApoAI mimetic of Co-pending 17/628418, one of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to substitute the APOA-I mimetic of Co-pending 17/628418, with instant SEQ ID NO:35 by Dasseux. One of ordinary skill in the art would have been motivated to do so because Dasseux teaches instant SEQ ID NO:35 is an ApoAI agonist peptide that can form HDL-like particles and adopt the required apha-heliclal conformation in lipid environments, the substitution would allow use of a well characterized, synthetically accessible, and functionally compatible mimetic peptide.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting SEQ ID NO:35 for the apoA-I protein of Co-pending 17/628418, because Dasseux demonstrates that the peptide forms lipid-associated, HDL-like particles and retains apoA-I biological function, including lipid binding and particle self-assembly. These properties directly align with the functional requirements of the synthetic HDL particle disclosed by Sparks.
As articulated in KSR Int’l Co. v. Teleflex Inc., when a claimed invention results from the substitution of one known element for another known, functionally equivalent element, and the substitution yields predictable results, the claimed invention is obvious. Here, substituting the known apoA-I protein of Co-pending 17/628418s with the known apoA-I mimetic peptide SEQ ID NO:35 taught by Dasseux represents a predictable substitution that results in formation of an HDL-like lipid nanoparticle suitable for therapeutic delivery. Such substitution would have been obvious to try with a reasonable expectation of success.
Instant Claims 2, 4, 7-11, 13, 16-17 are obvious over claims 1, 58, 85, 89 of Co-pending Application 17/628418 in view of Sparks (US6514523, cited in IDS) and Dasseux (US20030203842 A1).
This is a provisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
Applicant argues As to the provisional double patenting rejections, the instant application claims priority to PCT Application No. PCT/US2016/024230 and therefore has a patent term filing date of March 25, 2016. The remaining provisional double patenting rejections over the '418 application, the '456 application, the '230 application, and the '636 application are provisional, and each of these applications has a later patent term filing date than that of the instant application. Thus, as each other rejection and objection are addressed by this reply, the Applicant requests that the remaining provisional double patenting rejections be withdrawn to allow the instant case pursuant to M.P.E.P § 804(I)(B)(1)(b)(i).
Applicants arguments have been fully considered but not found persuasive. Given that the application is currently not allowable form, the provisional rejection is maintained.
Claims 2, 4, 7-11, 13, 16-17 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-20 of Co-pending 18/032456 in view of Sparks (US6514523, cited previously) and Dasseux (US20030203842)*cited previously.
The instant application claims “A composition comprising a synthetic high density lipoprotein_(HDL) - therapeutic agent (sHDL-TA) nanoparticle,wherein the sHDL comprises at least one therapeutic agent, at least one HDL apolipoprotein, and at least one phospholipid wherein the therapeutic agent is between 0.01 - 20% by weight of the sHDL-TA, and the sHDL is between 80-99.99% by weight of the sHDL-TA, and wherein the HDL apolipoprotein is an apolipoprotein A-I (apo A-I) mimetic having a sequence selected from the group consisting of: PPVLDWFRELLNELLEALKQKLK (SEQ ID NO: 35), PVLDLFRELLNEWLEALKQKLK (SEQ ID NO: 54), and PVLDEFRELLNELLEALKQKLK (SEQ ID NO: 79). The instant application further claims wherein the mimetic is one of SEQ ID Nos: 35, 54, 79; wherein the lipid is PC or DMPC (Claim 4); wherein the therapeutic is an anticoagulant, beta blocker, statin, Liver X R agonist (see claims 5-6, 14-15); further comprising an imaging agent (claims 9, 11, 17); 20% therapeutic, 80-99% sHDL (see claim 10); 6-20 nm particle size (see claim 7).
Co-pending 18/032456 claims “A composition comprising one or more synthetic HDL nanoparticle (SHDL) associated with (e.g., complexed, conjugated, encapsulated, absorbed, adsorbed, admixed) N- 2-benzothiazolyl-4-|[(2-hydroxy-3-methoxyphenyl)methy1]amino]-benzenesulfonamide (ML355) (SHDL-ML355) moieties, wherein the sHDL-ML355 (therapeutic) comprises a mixture of at least one lipid component, at least one HDL apolipoprotein component, and ML355” (see claim 1). Co-pending 18/032456 further claims HDL mimetic (see claims 4 and 9); DMPC (claim 5).
Co-pending 18/032456 doesn’t specifically claim (i) the concentrations of the therapeutic in the composition,(ii) inclusion of an imaging agent and (ii) SEQ ID NO:35.
However, Sparks teaches a composition comprising a synthetic HDL, wherein the synthetic HDL comprises Apo AI and a phospholipid (see abstract). Sparks teaches wherein the therapeutic agent is in the range of 1-20% (see column 6, lines 39-40) and provide an example of 20% drug and 80% sHDL (see Example 1) meeting the limitations of claim 117. Sparks teaches wherein the size of the particle is 5-20 nm (see abstract) and in particular 7.5 nm as a preferred diameter (see column 7, lines 14-16). Sparks discloses wherein the sHDL-therapeutic agent further comprises an imaging agent (Carbon-14) which meets the limitation of nuclear imaging agent.
It would have been obvious to optimize the amount of therapeutic in the particle to achieve optimal therapeutic efficacy. Furthermore, it would have been obvious before the invention to add an imaging agent to the sHDL nanoparticle of Co-pending 18/032456 to visualize intracellular delivery of the particle to determine effectiveness of the particle. There is a reasonable expectation of success given that imaging labels including radionuclides are commonly used to track the delivery of the sHDL.
Regarding instant SEQ ID NO:35, the teachings of Dasseux are provided in the above rejections.
Regarding instant SEQ ID NO:35 as the ApoAI mimetic of Co-pending Application 18/032456, one of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to substitute the APOA-I mimetic of Co-pending Application 18/032456 with instant SEQ ID NO:35 by Dasseux. One of ordinary skill in the art would have been motivated to do so because Dasseux teaches instant SEQ ID NO:35 is an ApoAI agonist peptide that can form HDL-like particles and adopt the required apha-heliclal conformation in lipid environments, the substitution would allow use of a well characterized, synthetically accessible, and functionally compatible mimetic peptide.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting SEQ ID NO:35 for the apoA-I protein of Co-pending Application 18/032456, because Dasseux demonstrates that the peptide forms lipid-associated, HDL-like particles and retains apoA-I biological function, including lipid binding and particle self-assembly. These properties directly align with the functional requirements of the synthetic HDL particle disclosed by Sparks.
As articulated in KSR Int’l Co. v. Teleflex Inc., when a claimed invention results from the substitution of one known element for another known, functionally equivalent element, and the substitution yields predictable results, the claimed invention is obvious. Here, substituting the known apoA-I protein of Co-pending Application 18/032456 with the known apoA-I mimetic peptide SEQ ID NO:35 taught by Dasseux represents a predictable substitution that results in formation of an HDL-like lipid nanoparticle suitable for therapeutic delivery. Such substitution would have been obvious to try with a reasonable expectation of success.
Instant claims 2, 4, 7-11, 13, 16-17 are obvious over claims 1-5, 8-20 Co-pending Application 18/032456 in view of Sparks and Dasseux
This is a provisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
Applicant argues As to the provisional double patenting rejections, the instant application claims priority to PCT Application No. PCT/US2016/024230 and therefore has a patent term filing date of March 25, 2016. The remaining provisional double patenting rejections over the '418 application, the '456 application, the '230 application, and the '636 application are provisional, and each of these applications has a later patent term filing date than that of the instant application. Thus, as each other rejection and objection are addressed by this reply, the Applicant requests that the remaining provisional double patenting rejections be withdrawn to allow the instant case pursuant to M.P.E.P § 804(I)(B)(1)(b)(i).
Applicants arguments have been fully considered but not found persuasive. Given that the application is currently not allowable form, the provisional rejection is maintained.
Claims 2, 4, 7-11, 13, 16-17 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 248-252 of Co-pending 19/088230 in view of Sparks (US6514523, cited previously).
The instant application claims “A composition comprising a synthetic high density lipoprotein_(HDL) - therapeutic agent (sHDL-TA) nanoparticle,wherein the sHDL comprises at least one therapeutic agent, at least one HDL apolipoprotein, and at least one phospholipid wherein the therapeutic agent is between 0.01 - 20% by weight of the sHDL-TA, and the sHDL is between 80-99.99% by weight of the sHDL-TA, and wherein the HDL apolipoprotein is an apolipoprotein A-I (apo A-I) mimetic having a sequence selected from the group consisting of: PPVLDWFRELLNELLEALKQKLK (SEQ ID NO: 35), PVLDLFRELLNEWLEALKQKLK (SEQ ID NO: 54), and PVLDEFRELLNELLEALKQKLK (SEQ ID NO: 79). The instant application further claims wherein the mimetic is one of SEQ ID Nos: 35, 54, 79; wherein the lipid is PC or DMPC (Claim 4); wherein the therapeutic is an anticoagulant, beta blocker, statin, Liver X R agonist (see claims 5-6, 14-15); further comprising an imaging agent (claims 9, 11, 17); 20% therapeutic, 80-99% sHDL (see claim 10); 6-20 nm particle size (see claim 7).
Co-pending 19/088230 claims “A composition comprising a nanodisc comprising a phospholipid selected from 1,2-dimyristol-sn-glycero-3-phosphocholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC), an apolipoprotein mimetic, and Substance P” (see claim 248). Co-pending 19/088230 further claims HDL mimetic, SEQ ID Nos:1-336 (see claims 250); DPPC (claim 248). SEQ IDNO:35 of the Co-pending 19/088230 is identical to instant SEQ ID NO:35.
Co-pending 19/088230 doesn’t specifically claim (i) the concentrations of the therapeutic (substance P) in the composition,(ii) inclusion of an imaging agent.
However, Sparks teaches a composition comprising a synthetic HDL, wherein the synthetic HDL comprises Apo AI and a phospholipid (see abstract). Sparks teaches wherein the therapeutic agent is in the range of 1-20% (see column 6, lines 39-40) and provide an example of 20% drug and 80% sHDL (see Example 1) meeting the limitations of claim 117. Sparks teaches wherein the size of the particle is 5-20 nm (see abstract) and in particular 7.5 nm as a preferred diameter (see column 7, lines 14-16). Sparks discloses wherein the sHDL-therapeutic agent further comprises an imaging agent (Carbon-14) which meets the limitation of nuclear imaging agent.
It would have been obvious to optimize the amount of therapeutic in the particle to achieve optimal therapeutic efficacy. Furthermore, it would have been obvious before the invention to add an imaging agent to the sHDL nanoparticle of Co-pending 19/088230 to visualize intracellular delivery of the particle to determine effectiveness of the particle. There is a reasonable expectation of success given that imaging labels including radionuclides are commonly used to track the delivery of the sHDL.
Instant Claims 2, 4, 7-11, 13, 16-17 are obvious over claims 248-252 of Co-pending 19/088230 in view of Sparks and Dasseux
This is a provisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
Applicant argues As to the provisional double patenting rejections, the instant application claims priority to PCT Application No. PCT/US2016/024230 and therefore has a patent term filing date of March 25, 2016. The remaining provisional double patenting rejections over the '418 application, the '456 application, the '230 application, and the '636 application are provisional, and each of these applications has a later patent term filing date than that of the instant application. Thus, as each other rejection and objection are addressed by this reply, the Applicant requests that the remaining provisional double patenting rejections be withdrawn to allow the instant case pursuant to M.P.E.P § 804(I)(B)(1)(b)(i).
Applicants arguments have been fully considered but not found persuasive. Given that the application is currently not allowable form, the provisional rejection is maintained.
Claims 2, 4, 7-11, 13, 16-17 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6, 15-16, 21, 23, 27, 35, 94, 97-98, 100-101 of Co-pending 18/840636 in view of Sparks (US6514523, cited previously).
The instant application claims “A composition comprising a synthetic high density lipoprotein_(HDL) - therapeutic agent (sHDL-TA) nanoparticle,wherein the sHDL comprises at least one therapeutic agent, at least one HDL apolipoprotein, and at least one phospholipid wherein the therapeutic agent is between 0.01 - 20% by weight of the sHDL-TA, and the sHDL is between 80-99.99% by weight of the sHDL-TA, and wherein the HDL apolipoprotein is an apolipoprotein A-I (apo A-I) mimetic having a sequence selected from the group consisting of: PPVLDWFRELLNELLEALKQKLK (SEQ ID NO: 35), PVLDLFRELLNEWLEALKQKLK (SEQ ID NO: 54), and PVLDEFRELLNELLEALKQKLK (SEQ ID NO: 79). The instant application further claims wherein the mimetic is one of SEQ ID Nos: 35, 54, 79; wherein the lipid is PC or DMPC (Claim 4); wherein the therapeutic is an anticoagulant, beta blocker, statin, Liver X R agonist (see claims 5-6, 14-15); further comprising an imaging agent (claims 9, 11, 17); 20% therapeutic, 80-99% sHDL (see claim 10); 6-20 nm particle size (see claim 7).
Co-pending 18/840636 claims “A method comprising administering to a subject:a composition comprising a nanoparticle; and a composition comprising an immunomodulatory agent capable of expanding regulatory T cells (Tregs) within the subject.” (see claim 1). Co-pending 18/840636 further wherein the nanoparticle is an sHDL nanoparticle comprising a mixture of at least one phospholipid and at least one HDL apolipoprotein or apolipoprotein mimetic (see claim 6, SEQ ID Nos:1-336, which SEQ ID NO:35 is the same as instant SEQ ID NO:35); a therapeutic agent, in particular a tolerogenic antigen (see claim 2)
Co-pending 18/840636 doesn’t specifically claim (i) the concentrations of the therapeutic (antigen) in the composition,(ii) inclusion of an imaging agent.
However, Sparks teaches a composition comprising a synthetic HDL, wherein the synthetic HDL comprises Apo AI and a phospholipid (see abstract). Sparks teaches wherein the therapeutic agent is in the range of 1-20% (see column 6, lines 39-40) and provide an example of 20% drug and 80% sHDL (see Example 1) meeting the limitations of claim 117. Sparks teaches wherein the size of the particle is 5-20 nm (see abstract) and in particular 7.5 nm as a preferred diameter (see column 7, lines 14-16). Sparks discloses wherein the sHDL-therapeutic agent further comprises an imaging agent (Carbon-14) which meets the limitation of nuclear imaging agent.
It would have been obvious to optimize the amount of therapeutic in the particle to achieve optimal therapeutic efficacy. Furthermore, it would have been obvious before the invention to add an imaging agent to the sHDL nanoparticle of Co-pending 18/840636 to visualize intracellular delivery of the particle to determine effectiveness of the particle. There is a reasonable expectation of success given that imaging labels including radionuclides are commonly used to track the delivery of the sHDL.
Instant Claims 2, 4, 7-11, 13, 16-17 are obvious over claims 1-3, 6, 15-16, 21, 23, 27, 35, 94, 97-98, 100-101 of Co-pending 18/840636 in view of Sparks.
This is a provisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
Applicant argues As to the provisional double patenting rejections, the instant application claims priority to PCT Application No. PCT/US2016/024230 and therefore has a patent term filing date of March 25, 2016. The remaining provisional double patenting rejections over the '418 application, the '456 application, the '230 application, and the '636 application are provisional, and each of these applications has a later patent term filing date than that of the instant application. Thus, as each other rejection and objection are addressed by this reply, the Applicant requests that the remaining provisional double patenting rejections be withdrawn to allow the instant case pursuant to M.P.E.P § 804(I)(B)(1)(b)(i).
Applicants arguments have been fully considered but not found persuasive. Given that the application is currently not allowable form, the provisional rejection is maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2, 4-5, 7-11, 13-14, 16-17 remain rejected under 35 U.S.C. 103 as being unpatentable over Sparks (USPN 6514523, cited in IDS) in view of Dasseux (US20030203842 A1, cited previously) and Zhang (Small 2010, 6, No. 3, 430–437, cited in IDS).
Sparks teaches a composition comprising a synthetic HDL, wherein the synthetic HDL comprises Apo AI and a phospholipid (see abstract). Sparks teaches wherein the therapeutic agent is in the range of 1-20% (see column 6, lines 39-40) and provide an example of 20% drug and 80% sHDL (see Example 1) meeting the limitations of claims 10. Sparks teaches wherein the apolipoprotein is APO A-I (see abstract and claim 7). Regarding claims 4, 13, Sparks teaches wherein the phospholipid comprises phosphatidylcholine (See Example 1, column 10). Regarding claims 2, 5, 14, Sparks teaches wherein the drug is an anticoagulant (see column 3, vitamin E for example) and also estradiol which is a vasodilator (see column 6, line 11). Regarding claims 7, 16, Sparks teaches wherein the size of the particle is 5-20 nm (see abstract) and in particular 7.5 nm as a preferred diameter (see column 7, lines 14-16). Regarding claims 8, 9, 11, 17, Sparks discloses wherein the sHDL-therapeutic agent further comprises an imaging agent (Carbon-14) which meets the limitation of nuclear imaging agent (see Figure 3, brief description). Furthermore, Sparks teaches wherein the therapeutic agent/imaging agent is 20% by weight of the sHDL (see Examples 1 and 3).
As stated above, Sparks teaches wherein the therapeutic agent is in the range of 1-20% (see column 6, lines 39-40) and provide an example of 20% drug and 80% sHDL (see Example 1) meeting the limitations of claim 10. Regarding the concentration of therapeutic, sHDL and imaging agent, MPEP states that "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005) (claimed alloy held obvious over prior art alloy that taught ranges of weight percentages overlapping, and in most instances completely encompassing, claimed ranges; furthermore, narrower ranges taught by reference overlapped all but one range in claimed invention). MPEP § 2144.08. Furthermore, it would have been obvious to optimize the amount of therapeutic/imaging agent in the particle to achieve optimal therapeutic efficacy.
Sparks is silent to wherein the Apolipoprotein A-I is an Apo A-I mimetic and comprises instant SEQ ID NO:35.
However, Dasseux teaches ApoA-I agonist peptides that are designed to mimic the structure and biological activity of native apoA-I (see Abstract, paragraphs 0001-0002). Dasseux teaches that the disclosed ApoA-I agonist peptides form amphipathic alpha helices in the presence of lipids (see paragraph 0001, 0084, 088); bind phospholipids and form HDL-like or pre-B-HDL like complexes (see paragraphs 0014, 0042, 0044, 0084); associate with the HDL component in plasma and increase HDL and pre-BHDL particles (see paragraphs 0084-0086). Dasseux expressly discloses ApoA-I mimetic peptide sequences SEQ ID Nos:35, 54, 79, which are identical to the sequences recited in claims 2 and 11 (see claim 19; paragraph 0019; claims 19 and 42). Dasseux further teaches that these ApoAI agonist peptides are formulated as peptide lipid complexes, including phospholipid complexes that are suitable for parenteral administration and form HDL-like particles (see paragraphs 0042-0046, 0081-0083, 0397-0402, see also Figure 11).
Zhang teaches HDL-mimicking Peptide-Lipid nanoparticles (see title). High-density lipoprotein (HDL) is an endogenous nanocarrier possessing many of these attractive features. It possesses ultrasmall size control (7–12 nm) through the apoA-1 lipoprotein component and favorable surface properties. This unique combination results in long circulation half-lives ranging from 10 to 12 h in rodents and 5 days in humans (see page 431, left column, second paragraph). Zhang further teaches wherein the ApoA-I protein component of the nanocarrier is an Apo A-I mimetic peptide (see page 431, left column, last paragraph, section 2.1).
One of ordinary skill in the art, prior to the effective filing date of the claimed invention, would have been motivated to substitute the apoA-I protein taught by Sparks with SEQ ID NO:35 taught by Dasseux. Such motivation arises because Dasseux expressly teaches that SEQ ID NO:35 is an apoA-I agonist peptide that mimics the structure and biological activity of native apoA-I, including adoption of an amphipathic α-helical conformation in lipid environments and self-assembly with phospholipids into HDL-like particles (see Dasseux, Abstract; ¶¶ [0001], [0084]–[0086]). Dasseux further teaches that apoA-I mimetic peptides form discoidal peptide–lipid complexes, as illustrated in FIG. 11, which are structural analogs of synthetic HDL particles. Accordingly, Dasseux teaches that SEQ ID NO:35 is functionally compatible with lipid-based HDL-mimicking nanoparticles and is capable of forming stable particles in the presence of phospholipids.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting SEQ ID NO:35 for the ApoA-I protein of Sparks, because Dasseux demonstrates that the peptide forms lipid-associated, HDL-like particles and retains apoA-I biological function, including lipid binding and particle self-assembly. These properties directly align with the functional requirements of the synthetic HDL particle disclosed by Sparks.
Furthermore, Zhang teaches that apoA-I mimetic peptides may be used as the apolipoprotein component in HDL-mimicking peptide–lipid nanoparticles, further reinforcing that apoA-I and apoA-I mimetic peptides were recognized in the art as interchangeable components in HDL-like nanocarriers.
As articulated in KSR Int’l Co. v. Teleflex Inc., when a claimed invention results from the substitution of one known element for another known, functionally equivalent element, and the substitution yields predictable results, the claimed invention is obvious. Here, substituting the known apoA-I protein of Sparks with the known apoA-I mimetic peptide SEQ ID NO:35 taught by Dasseux represents a predictable substitution that results in formation of an HDL-like lipid nanoparticle suitable for therapeutic delivery. Such substitution would have been obvious to try with a reasonable expectation of success.
Response to Applicant’s Arguments
Applicant argues it sparks itself provides no suggestion to substitute an APO-A1 mimetic peptide for an ApoAI or ApoAII and does not disclose SEQ ID numbers 35, 54 or 79. Applicants arguments have been fully considered but not found persuasive. The rejection does not rely upon sparks alone to teach the presently claimed Apo AI memetic peptide sequences. Sparks has relied upon for the teaching the synthetic HDL nanoparticle comprising an apolipoprotein and phospholipid and incorporating A therapeutic agent including the amounts of particle characteristics identified in the rejection. Dasseux is relied upon for teaching Apo AI memetic peptides including the particular sequences recited in instant claims 2 and 11 and their ability to associate with lipids to form HDL like complexes. Saying further evidence is the known use of Apo AI memetic peptides as components of HDL mimicking peptide lipid nanoparticles.
Obviousness is determined based upon the combined teachings of the prior art rather than whether the primary reference individually contains every claim feature. Thus the absence from sparks of the particular memetic peptide sequence does not render the proposed combination non obvious (see MPEP 2145, Arguing references individually).
Applicant argues that Dasseux would have directed the skilled artisan away from SEQ ID Nos:35, 54, and 79 because those sequences exhibit only 31%, 19% and 9% LCAT activation, respectively, whereas Dasseux identifies peptides having At least about 38% LCAT activation as preferred and particularly prefers still greater LCAT activation.
Applicants argument has been fully considered but not found persuasive. This argument focuses on a property that is not the basis for the proposed modification of Sparks. The office does not rely upon SEQ ID Nos: 35, 54 and 79 because those sequences provide superior LCAT activation. Nor do claims 2 and 11 require particular degree of LCAT activation. Dasseux is relied upon for its teaching of APOAI mimetic peptides having properties pertinent to the formation of HDL like lipid particles. As set forth in the rejection, Dasseux teaches ApoAI agonist peptides designed to mimic structural and biological properties of ApoAI including adoption of amphipathic alpha helical conformations, lipid environments, lipid phospholipid association and formation of pre beta HDL like or HDL like complexes.
These teachings are relevant to the proposed modifications because the ApoAI component of sparks functions as a component of a synthetic HDL lipid particle. Accordingly the pertinent question is not whether the peptides exhibit the greatest LCAT activation among peptides but whether the prior art would have provided reason to employ an ApoAI mimetic having the lipid associating and HDL particle forming characteristics that are required for use in an HDL like nanoparticle.
Applicants identification of other Dasseux peptides having greater L cat activation therefore does not establish that the clean peptides would have been unsuitable for the function of which they are employed in the proposed combination. Furthermore the mere disclosure of a preferred embodiment does not necessarily exclude or discourage less preferred embodiments. The fact that Dasseux identifies peptides having higher lcat activity as preferred does not without more establish that Dasseux teachers that lower lcat peptides are incapable of lipid association or HDL like particle formation (see MPEP2123). MPEP 2123 states “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have "relatively acceptable dimensional stability" and "some degree of flexibility," but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since "Gurley asserted no discovery beyond what was known in the art." Id. at 554, 31 USPQ2d at 1132.). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).”
Applicant relies upon Dasseux’s statement that previously known ApoAI memetic peptides having less than approximately 40% of APOAI’s LCAT activity has not been demonstrated to be useful as drugs. Apple contends that a skilled artisan therefore would not have selected the peptides of the instant claims for therapeutic purposes.
Applicants arguments have been fully considered but not found persuasive. In the proposed combination the therapeutic agent is carried by the SHDL nanoparticle taught by sparks. The Dasseux peptide Is substituted for the native ApoAI as the mimetic apolipoprotein component of the lipid nanoparticle. Thus whether a particular ApoAI memetic would itself have been referred as an independently active therapeutic drug does not resolve whether it would have been useful as a structural lipid associating component of an HDL like nanoparticle carrying another therapeutic agent. Applicant therefore conflates two different functions therapeutic activity attributable to ApoAI/LCAT activation and the ability of an ApoAI mimetic peptide to participate in the formation of an HDL like peptide lipid particle.
Applicant argues that the claim sequences exhibit lower helicity than other Dasseux peptides and therefore a skilled artisan would have selected peptides having greater helicity and or greater lcat activation.
Applicants arguments have been fully considered but not found persuasive. The existence of alternatives exhibiting quantitatively greater helicity of or lcat activation does not establish that the presently claimed sequences were unsuitable for lipid association or formation of HDL like particles. The obviousness inquiry does not require showing that the claimed alternatives was the optimum or most preferred alternative known in the art. The rejection instead relies upon the prior arts teachings concerning the functional suitability of ApoAI memetics for HDL like lipid systems and Dasseux’s express disclosure of the presently recited sequences. Applicants showing that other peptides may exhibit superior performance according to other metrics does not negate the reason to use an expressly disclosed memetic peptide for the lipid particle forming function relevant to sparks.
Applicant argues that Zhang discloses only a single ApoAI memetic peptide which differs from the claimed peptides. Applicant therefore contends that Zhang cannot provide a reason to select the claimed Dasseux sequences. Applicants arguments have been fully considered but not found persuasive. Saying is not relied upon to disclosed the peptides of the instant claims. Dasseux teaches those sequences. Zhang is not relied upon to establish the lcat activity of those sequences. Rather Zhang is relied upon as evidence that APO AI memetic peptides were known in the art to be employed as the peptide apolipoprotein component of HDL mimicking peptide lipid nanoparticles. The fact that Zhang’s particular memetic peptide has a different amino acid sequence does not negate Zhang’s relevant teaching that an APOAI mimetic peptide can be employed in constructing an HDL mimicking peptide lipid nanoparticle.
The applicant argues that Zhang’s peptide lacks the leucine substitutions that Dasseux describes as providing particular APOAI like structural and functional properties. Applicant contends that Zhang therefore would not have suggested using the peptides of Dasseux.
Applicants arguments have been fully considered but not found persuasive. The references are relied upon for complementary teachings. Dasseux supplies the particular mimetic sequences that teach their mimetic lipid related properties. Zhang supplies evidence that ApoAI mimetic peptides were known for use as components of HDL mimicking peptide lipid nanoparticles.
Applicant argues that the references provide no motivation to specifically select one of SEQ ID Nos. 35, 54 or 79 from among Dasseux’s peptides because the other peptides exhibit superior lcat activation and or Helicity.
Applicants arguments have been fully considered but not found persuasive. The proposed combination does not arise merely from the fact that the claim sequences can be located somewhere within Dasseux. Rather, Dasseux expressly identifies the claim sequences within its disclosure of ApoAI mimetic peptides while also teaching the lipid associating and HDL like complex forming characters of its mimetics. Sparks provides A synthetic HDL therapeutic agent delivery particle employing ApoAI and phospholipid while Zhang demonstrates the known use of ApoAI mimetic peptides in HDL mimicking peptide lipid nanoparticles.
Taken together these teachings would have provided a person of ordinary skill with reason to substitute in Apoa I mimetic taught by Dasseux for the ApoAI mimetic used by Sparks in order to provide an HDL like peptide lipid nanoparticle suitable for incorporation of the therapeutic agent with a reasonable expectation that an ApoAI mimetic possessing the disclosed lipid associating HDL forming properties would perform the particle forming function. The fact that Dasseux identifies other peptides as preferred according to lcat activation does not negate this rationale because maximizing lcat activation is not the objective of the proposed modification it is not a limitation of claims to or 11.
Claim(s) 2, 4-11, 13-17 remain rejected under 35 U.S.C. 103 as being unpatentable over Sparks (US6514523, cited in IDS) in view of Dasseux (US20030203842 A1) and Zhang (Small 2010, 6, No. 3, 430–437, cited in IDS) as applied to Claim(s) 2, 4-5, 7-11, 13-14, 16-17 above, in further view of Ackermann (EP2673296 B1, cited in IDS).
The teachings of Sparks in view Dasseux and Zhang are provided in the above rejection.
Additionally Sparks teaches that “The present invention provides carrier particles which are small in size and not easily recognized as foreign by the body for drug delivery of hydrophobic, amphipathic, or cationic lipophilic drugs. The present invention further provides a process for preparing carrier particles comprising drugs. It is an object of the invention to circumvent drawbacks in hydrophobic drug delivery described in the prior art” (see column 2, lines 57-64). The teachings of Sparks in view of Dasseux and Zhang are silent to wherein the therapeutic agent is isotretinoin (retinoid X receptor agonist).
However, Ackermann teaches a composition comprising a lipid fraction and Apo A-I (see claim 1). Ackermann teaches wherein the composition further comprises a hydrophobic, hydrophilic active agent and wherein the active agent is isotretinoin (see claim 22) and wherein the composition comprises an imaging agent (see claim 25). Ackermann teaches additional therapeutic agents including statins (see paragraph 0188, claim 22).
It would have been obvious before the effective filing date of the claimed invention to incorporate vitamin A and/or isotretinoin as the therapeutic agent within the sHDL nanoparticle, as taught by Ackermann, because Sparks teaches sHDL nanoparticles as delivery vehicles for hydrophobic and lipophilic drugs, and Ackermann teaches that vitamin A compounds and isotretinoin are compatible therapeutic agents for HDL-based delivery systems. A person of ordinary skill in the art would have had a reasonable expectation of success, as each reference teaches structurally and functionally compatible components, namely HDL or HDL-mimetic lipid nanoparticles, ApoA-I or ApoA-I mimetic peptides, and lipophilic therapeutic agents. Under KSR Int’l Co. v. Teleflex, the claimed invention represents the substitution of one known element (isotretinoin or vitamin A from Ackermann) into a known delivery platform (sHDL nanoparticles from Sparks in view of Dasseux and Zhang) to obtain a predictable result, namely delivery of a lipophilic therapeutic agent via an HDL-based nanoparticle. Such substitution constitutes routine optimization and would have been obvious to try with a reasonable expectation of success.
Response to Applicant’s Arguments
Applicant argues that Ackermann does not cure the alleged deficiencies of sparks, Dasseux and Zhang because Ackerman does not disclose the specific sequences of the instant claims and describes APOAI memetics by reference to activation of LCAT.
Applicants argument has been fully considered but not found persuasive. Ackerman is not relied upon to supply the claimed sequences. Those sequences are supplied by Dasseux. Rather Ackerman is relied upon in the additional rejection for the therapeutic agent teachings identified in the office action including the use of isotretinoin/Vitamin A compounds in an HDL based delivery composition. Thus applicants observation that Ackerman does not disclose the sequences does not address the teaching for which Ackerman is applied. Ackerman's discussion of LCAT activation does not negate the combined teachings of sparks, Dasseux and Zhang concerning formation of HDL like lipid nanoparticles using ApoAI mimetic peptides. The proposed modification does not require selection of a peptide for maximum LCAT activation.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
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