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 .
This office action is Non-Final. The finality of the last Office action dated 9/25/2023 is withdrawn due to the Appeal Board Decision dated 9/25/2025.
Claim Status
Claims 1, 3-10, 13-15, 17-25 and 34-37 are pending.
Claims 2, 11-12, 16, and 26-33 were cancelled.
Claims 1, 5 and 25 are amended and claims 34-37 are new.
Claims 14-15 and 17-24 are withdrawn as being directed to a non-elected method invention, the election having been made on 12/24/2019. The new claim 37 is further withdrawn because applicant’s elected compound of l-tetradecanoyl-sn-glycero-3-phosphocholine (lyso 14:0) does not contain an unsaturated hydrocarbon chain with one or more double bonds between carbon atoms.
Claims 1, 3-10, 13, 25, and 34-36 have been examined.
Priority
This application is a 371 of PCT/US2017/042307 07/17/2017.
PCT/US2017/042307 has PRO 62/363,395 07/18/2016.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/23/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Rejection
The rejection of claims 11-12, 26-33 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn because applicant canceled the claims.
The rejection of claim 12 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn because applicant canceled the claims.
The rejection of claim 25 under 35 U.S.C. 112(b) in the appeal broad’s decision is withdrawn because the amendment to claim 25 overcomes the rejection.
New Ground of Objection and Rejection
Claim Objection
Claims 5, 8-9, and 36 are objected to because of the following informalities:
Claim 5 is objected to because “wherein a molar percent ratio” should be “wherein the molar percent ratio”.
Claim 8 is objected to because the image resolution of compound formulas I, II, IV, and V is poor. The examiner requests applicant to provide clear image of the compound formulas. Furthermore, R1 and R2 recited in claim 8 should be R1 and R2 shown in Formula (I).
Claim 9 is objected to because the image resolution of compound formulas Ia, II, IV, and V is poor. The examiner requests applicant to provide clear image of the compound formulas.
Claim 36 contains the acronym “CMC”, and an acronym in the first instance of claims should be expanded upon/spelled out as “Critical Micelle Concentration” with the acronym indicated in parentheses as (CMC). The abbreviations can be used thereafter.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-10, and 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a NEW MATTER rejection.
Contain 1 contains a limitation “wherein the lysolipid is configured to be displaced by a hydrophobic drug” not supported by the specification of record. Applicant’s remarks argues paragraphs 00124, 00129, and 00171 support the limitation, but the examiner did not find evidence sufficient to support “the lysolipid is configured to be displaced by a hydrophobic drug”.
[00124] disclosed few hydrophobic drug, but not support “the lysolipid is configured to be displaced by a hydrophobic drug”. In particular, the disclosed drug examples do not represent the entire genus of a hydrophobic drug and the specification did not disclose how to determine the precise location of a lysolipid in the nanolipoprotein particle.
[00129] disclosed “the hydrophobic drugs can displace the lysolipids from the formed NLPs once the drugs are incorporated and the lysolipids will be expulsed from the assembled NLPs.” There is insufficient disclosure to support “the lysolipid is configured to be displaced by a hydrophobic drug” because the specification failed to establish correlation between a configured lysolipid and a hydrophobic drug able to displace the configured lysolipid. For instant, a specific displacement of a lysolipid by a hydrophobic drug may need to be performed under a particular condition (temperature, pH, or salt concentration) or in the presence of additional reagent (e.g., detergent).
[00171] disclosed paclitaxel can displace the lysophospholipids from the particle upon
incorporation, but paclitaxel does not represent the entire genus of a hydrophobic drug. Since applicant failed to establish correlation between a configured lysolipid and a hydrophobic drug, there is no evidence that all hydrophobic drugs can displace lysolipids.
Claims 3-13 are rejected as depending on claim 1.
Modified Rejection
Claim Rejections - 35 USC § 103
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.
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.
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.
1. Claims 1, 4-10, 13, 25, and 34-36 are rejected under 35 U.S.C. 103 as being unpatentable over Shelness (US 2003/0008014 Al, previously cited 1/31/2020) in view of Watkin (US 2006/0127467 A1, previously cited 1/31/2020) and evidenced by (a) Ryan et al. (Expert Opin. Drug Deliv. (2008) 5(3):343-351) and (b) Zhang et al. (US 2005/0175683).
Claim 1 is drawn to a nanolipoprotein particle comprising:
a membrane forming,
lipid, a lysolipid., and
a scaffold protein,
the membrane forming lipid and the lysolipid arranged in a discoidal membrane forming lipid bilayer stabilized by the scaffold protein,
the discoidal membrane forming lipid bilayer comprising the lysolipid in a molar
concentration of about 10 to about 70 mol%.,
wherein the lysolipid is configured to be displaced by a hydrophobic drug.
The wherein clause (vi) neither change the structure of a lysolipid nor a hydrophobic drug structure. Furthermore, if the wherein clause is intended to introduce a process of making the nanolipoprotein particle, the claims is examined as a product not a method.
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Shelness teaches a nanolipoprotein particle comprising: a membrane forming lipid and a recombinant scaffold protein arranged in a discoidal membrane of lipid bilayer, and recombinant discoidal complexes with a nanodisk structure are formed in the presence of apoB17F [0032] shown in figure 4 above, reading on the limitations of (i) and (iii). Shelness teaches the lipid composition further comprising at least one polar lipid, such as lysolipid, to form the nanolipoprotein complex [0054, claim 14], reading on the limitation (ii). Shelness shows the membrane forming lipid and the lysolipid arranged in a discoidal membrane forming lipid bilayer stabilized by the scaffold protein above (Fig 4).
Shelness does not specify a molar ratio of a lysolipid in the membrane of a nanolipoprotein particle.
Similarly, Watkin teaches the use of a lipid based nanoparticle (e.g., a nanolipoprotein particle of nanodisk) or a liposome as a drug carrier [Abstract, 0006, claim 2]. Watkin teaches a lipid bilayer or membrane of the lipid nanoparticle comprising a primary phospholipid (reading on membrane forming lipid) and a lysolipid [0006]. Watkin teaches the lysolipid may have a chain length ranging from about 6 to 24 carbon atoms, with a preferred chain length of about 14
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carbon atoms [0027], such as l-tetradecanoyl-snglycero-3-phosphocholine (lyso14:0; the elected lysolipid species), shown as follows[Fig 3b]. Watkin suggests the molar ratio of phospholipid to the lysolipid is a result effective variable ranged from 80:20 to about 95:5 and preferably about 90: 10 [0030], reading on the limitations (ii), (iv), and (v).
Ryan et al. is cited to show nanodisks (NDs) as hydrophobic drug delivery vehicles known in the art (Title). Ryan et al. show the common knowledge of nanodisks as hydrophobic drug delivery vehicles comprising (a) the edge of the ND is stabilized through apolipoprotein, a scaffold protein, binding to the disk perimeter (p344, Fig 1, legend), (b) NDs do not possess an aqueous core (c) scaffold proteins constitute an intrinsic structural element of NDs, (d) ND diameters much smaller than liposome, and (e) unlike liposomes, NDs are fully soluble in aqueous media (p344, col 1, 1.1 Nanodisk structure). Thus, one of ordinary skill in the art would have known different properties between Shelness’s ND and liposome are (a)-(e) listed above even though they may contain the same phospholipids and lysolipids. Zhang et al. is further cited to show common knowledge that lysolipids, e.g., lysophosphatidylcholine, having one hydrocarbon chain serves as surfactant (not a lipid bilayer forming lipid) in a lipid bilayer vesicle [0035-0036].
With respect to limitation (vi), Shelness in view of Watkin teaches a nanolipoprotein particle (nanodisk known in the art) comprising a membrane forming lipid, a lysolipid, and a recombinant scaffold protein. Lysolipids, e.g., lysophosphatidylcholine, having one hydrocarbon chain serves as surfactant in a lipid bilayer vesicle known in the art evidenced by Zgang et al. [0035-0036]. One of ordinary skill in the art would have known to optimize the amount of lysolipid in the nanolipoprotein particle (nanodisk) below critical micelle concentration of the lysolipid (CMC) to avoid micelle formation according to Watkin’s suggestion for the molar ratio of phospholipid to the lysolipid is a result effective variable ranged from 80:20 to about 95:5 and preferably about 90:10 [0030], reading on the limitations (i)-(v) described above. The specification [00129] disclosed “once the drugs are incorporated and the lysolipids will be expulsed from the assembled NLPs”, that is too say, if lysolipids are not excluded then a hydrophobic drug CANNOT be incorporated into the nanolipoprotein particle. Since Shelness’s hydrophobic drug of paclitaxel incorporated into the nanolipoprotein particle (Fig 4) is the same drug used by applicant [00165-00166], the limitation (vi) is necessary to be satisfied in the nanolipoprotein particle (nanodisk) taught by Shelness in view of Watkin, reading on claims 1 and 6.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Shelness's nanolipoprotein bilayer particle with Watkin's lysolipid of 1-tetradecanoyl-snglycero phosphocholine (lyso14:0) because (i) Shelness teach a lipid bilayer nanolipoprotein particle comprising a lysolipid as a drug carrier [0054] and (ii) Watkin teaches the use of lysolipid 14:0 of l-tetradecanoyl-snglycero-3-phosphocholine (Fig 3b) compatible with phospholipid to make a lipid bilayer of a drug delivery vehicle. The combination would have reasonable expectation of success because both references teach lysolipid in a lipid bilayer of drug delivery vehicle.
Ryan et al. is cited as evidence to show the common knowledge of nanodisks as hydrophobic drug delivery vehicles (p344, col 1, 1.1 Nanodisk structure). Zhang et al. is further cited as evidence to show common knowledge that lysolipids having one hydrocarbon chain serves as surfactant in a lipid bilayer vesicle [0035-0036].
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With respect to claims 4-5, Shelness teach the truncated scaffold protein can be optimized from 0.5% to 90% [0073]. Shelness further teaches apoB is capable of stabilizing the bilayer particle for controlling the size of the nanolipoprotein particle [0065, Fig 4]. Thus, the molar ratio of a scaffold protein in a nanolipoprotein bilayer particle is a result effective variable, which can be optimized through routine experimentation. MPEP 2144.05 (II) states “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).”
With respect to claims 7-10, Watkin show the lysolipid (Fig 3b) is l-tetradecanoyl-snglycero-3-phosphocholine (lyso14:0; the elected lysolipid species), reading on the elected species in claims 7-10.
With respect to claim 13, Shelness teaches truncated apoB as a fusion protein with a single chain antibody, ligand or receptor, or any other peptide sequence that would be specific for a particular macromolecular cell surface marker [0024]. Shelness teaches the use of truncated apoB to compartmentalize lipophilic drugs, such as paclitaxel in a nanolipoprotein particle [0018, Fig 2-4], reading on a functionalized amphipathic compound.
With respect to claim 25, Shelness in view of Watkin teach a nanolipoprotein particle and a process of making the nanolipoprotein. Shelness teaches a system comprising a membrane forming lipid of phospholipids and lysolipids [0054] as well as a scaffold protein [0058]. Shelness shows upon assembly the one or more membrane forming lipids and the scaffold protein provide a discoidal membrane lipid bilayer for the nanolipoprotein particle in which the one or more lysolipids are comprised within the discoidal membrane lipid bilayer in the sustem (Fig 4). Shelness shows the scaffold protein able to stabilize phospholipids and lysolipids in the system in figure 4 (known as nanodisk/ND) and further evidenced by Ryan’s teaching that the edge of ND is stabilized through apolipoprotein binding to the disk perimeter (p344, Fig 1, legend). Watkin suggests the molar ratio of phospholipid to the lysolipid is a result effective variable ranged from 80:20 to about 95:5 and preferably about 90: 10 [0030] in the system. Watkin teaches the lysolipid in the system may have a chain length ranging from about 6 to 24 carbon atoms, with a preferred chain length of about 14 carbon atoms [0027], such as l-tetradecanoyl-snglycero-3-phosphocholine (lyso14:0; the elected lysolipid species), shown in figure 3b. Also See rejection of claim 1 above.
With respect to claim 34, see rejection of claim 1 above. Claim 34 has broader claim scope than the rejected claim 1 above.
With respect to claim 35, Watkin teaches the lysolipid may have a chain length ranging from about 6 to 24 carbon atoms, with a preferred chain length of about 14 carbon atoms [0027], such as l-tetradecanoyl-snglycero-3-phosphocholine (lyso14:0; the elected lysolipid species), comprising a chain length of 14 carbons [Fig 3b].
With respect to claim 36, Zhang et al. is cited to show common knowledge that lysolipids, e.g., lysophosphatidylcholine, having one hydrocarbon chain serves as surfactant in a lipid bilayer vesicle [0035-0036]. One of ordinary skill in the art would have known to optimize the amount of lysolipid in the nanolipoprotein particle (nanodisk) below critical micelle concentration of the lysolipid (CMC) to avoid micelle formation. Furthermore, Watkin’s lysolipid of l-tetradecanoyl-snglycero-3-phosphocholine (lyso14:0; the elected lysolipid species) has the CMC value of 80 µM disclosed in the specification [00180].
Applicant’s Arguments
Shelness does not and would not disclose Shelness's phospholipids being displaced by the lipophilic compound (Remarks, p12, last para to p13,para 1-2).
Response to Arguments
Applicant's arguments filed 11/15/2025 have been fully considered but they are not persuasive for the reasons as follows.
The argument is not persuasive because of the following reasons.
The wherein clause (vi) neither change the structure of a lysolipid nor a hydrophobic drug structure. If the wherein clause is intended to introduce a process of making the nanolipoprotein particle, the claims is examined as a product not a method.
The specification [00129] disclosed “once the drugs are incorporated and the lysolipids will be expulsed from the assembled NLPs” [00129], that is too say, if lysolipids are not excluded a hydrophobic drug CANNOT be incorporated into the nanolipoprotein particle. Since Shelness shows the hydrophobic drug of paclitaxel, the same drug used by applicant [00165-00166], successfully incorporated into the nanolipoprotein particle (nanodisk) in figure 4, the lysolipids must be expulsed by the incorporated paclitaxel.
2. Claims 1, 3-10, 13, 25, and 34-36 are rejected under 35 U.S.C. 103 as being unpatentable over Shelness (US 2003/0008014 Al, previously cited 1/31/2020) in view of Leigh et al. (US 6599527 B1, previously cited 1/31/2020) and evidenced by (a) Ryan et al. (Expert Opin. Drug Deliv. (2008) 5(3):343-351), (b) Zhang et al. (US 2005/0175683), and (c) Zoac et al. (Arterioscler Thromb. 1994 Apr;14(4):567-75).
Claim 1 is drawn to a nanolipoprotein particle comprising:
a membrane forming,
lipid, a lysolipid., and
a scaffold protein,
the membrane forming lipid and the lysolipid arranged in a discoidal membrane forming lipid bilayer stabilized by the scaffold protein,
the discoidal membrane forming lipid bilayer comprising the lysolipid in a molar
concentration of about 10 to about 70 mol%.,
wherein the lysolipid is configured to be displaced by a hydrophobic drug.
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Shelness teaches a nanolipoprotein particle comprising: a membrane forming lipid and a recombinant scaffold protein arranged in a discoidal membrane of lipid bilayer, and recombinant discoidal complexes with a nanodisk structure are formed in the presence of apoB17F [0032] shown in figure 4 above, reading on the limitations of (i) and (iii). Shelness teaches the lipid composition further comprising at least one polar lipid, such as lysolipid, to form the nanolipoprotein complex [0054, claim 14], reading on the limitation (ii). Shelness shows the membrane forming lipid and the lysolipid arranged in a discoidal membrane forming lipid bilayer stabilized by the scaffold protein above (Fig 4).
Shelness does not specify a molar ratio of a lysolipid in the membrane of a nanolipoprotein particle.
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Similarly, Leigh et al. teach the use of a lipid bilayer comprising a mixture of membrane forming lipid and lysolipid for drug delivery (Fig 1B). Leigh et al. show that phosphatidylcholine (PC) to a lysophospholipid of mono-acyl phosphatidyl choline (MAPC) at an optimized ratio of 60:40 can beneficially increase the amount of a delivered lipophilic drug carried by the nanolipoprotein particle (Fig 10), reading on the limitation of lysolipid in a molar concentration of about 10 to about 70 mol%. Leigh et al. suggest the phosphatidyl choline (PC) and monoacyl phosphatidyl choline (MAPC) are endogenous compounds (col 6, line 2-3). The common endogenous fatty acids are palmitate (linear C16) or myristic acid (linear C14) well-known in the art. Leigh's mono-acyl phosphatidyl choline (MAPC) reads on the compound formulas (I) and (Ia) shown as follows; wherein R1 is C13 or C15 alkyl. When R1=C13, Q1=Q2=O, n=1, 0=0, m=2, R21=H, and Z= choline, the compound formula reads on a lysolipid of l-tetradecanoyl-snglycero-3-phosphocholine (lyso14:0 with CPC of 80 µM as disclosed in the specification [00180]), reading on the limitation of a lysolipid with CMC value ranging between 0.0005 to 100 mM. Because both Shelness and Leigh et al. teach a lipid bilayer drug delivery vehicle comprising phospholipid and lysolipid, one of ordinary skill in the art would have found it obvious to use phosphatidylcholine (PC) to a lysophospholipid of mono-acyl phosphatidyl choline (MAPC) at ratio of 60:40 to increase the amount of a delivered lipophilic drug carried by the nanolipoprotein particle (Fig 10), reading on the limitations of (ii), (iv), and (v).
Ryan et al. is cited to show nanodisks (NDs) as hydrophobic drug delivery vehicles known in the art (Title). Ryan et al. show the common knowledge of nanodisks as hydrophobic drug delivery vehicles comprising (a) the edge of the ND is stabilized through apolipoprotein binding to the disk perimeter (p344, Fig 1, legend), (b) NDs do not possess an aqueous core (c) scaffold proteins constitute an intrinsic structural element of NDs, (d) ND diameters much smaller than liposome, and (e) unlike liposomes, NDs are fully soluble in aqueous media (p344, col 1, 1.1 Nanodisk structure). Thus, one of ordinary skill in the art would have known major different properties between Shelness’s ND and liposome are (a)-(e) listed above even though they may contain the same phospholipids and lysolipids. Zhang et al. is cited to show common knowledge that lysolipids, e.g., lysophosphatidylcholine, having one hydrocarbon chain serves as surfactant in a lipid bilayer vesicle [0035-0036].
With respect to limitation (vi), Shelness in view of Leigh teaches a nanolipoprotein particle (nanodisk known in the art) comprising a membrane forming lipid, a lysolipid, and a recombinant scaffold protein. Lysolipids, e.g., lysophosphatidylcholine, having one hydrocarbon chain serves as surfactant in a lipid bilayer vesicle known in the art evidenced by Zgang et al. [0035-0036]. One of ordinary skill in the art would have known to optimize the amount of lysolipid in the nanolipoprotein particle (nanodisk) below critical micelle concentration of the lysolipid (CMC) to avoid micelle formation as applied to the limitations (i)-(v) above. The specification [00129] disclosed “once the drugs are incorporated and the lysolipids will be expulsed from the assembled NLPs.” Since Shelness’s hydrophobic drug of paclitaxel (Fig 4) is the same drug used by applicant [00165-00166], the limitation (vi) is necessary to be in the nanolipoprotein particle (nanodisk) as taught by Shelness in view of Leigh.
Thus, Shelness in view of Leigh et al. and evidenced by (a) Ryan et al. and (b) Zhang et al. are obvious to the instant claims 1, 3, and 6.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Shelness's nanolipoprotein bilayer particle with Leigh's lysolipid of 1-tetradecanoyl-snglycero phosphocholine (lyso14:0) because (i) Shelness teach a lipid bilayer nanolipoprotein particle comprising a phospholipid (e.g., phosphatidylcholine) and a lysolipid as a drug delivery vehicle of a nanolipoprotein [0054] and (ii) Leigh et al. show that phosphatidylcholine (PC) to a lysophospholipid of mono-acyl phosphatidyl choline (MAPC) at an optimized ratio of 60:40 can beneficially increase the amount of a delivered lipophilic drug carried by the nanolipoprotein particle (Fig 10). The combination would have reasonable expectation of success because both references teach the use of a nanolipoprotein comprising phosphatidylcholine and lysophospholipid to deliver a hydrophobic or lipophilic drug.
Ryan et al. is cited as evidence to show the common knowledge of nanodisks as hydrophobic drug delivery vehicles (p344, col 1, 1.1 Nanodisk structure). Zhang et al. is further cited as evidence to show common knowledge that lysolipids having one hydrocarbon chain serves as surfactant in a lipid bilayer vesicle [0035-0036]. Zoac et al. is further cited as evidenced to show endogenous fatty acids of palmitate (linear C16) or myristic acid (linear C14) well-known in the art by (p567, col 1).
With respect to claims 4-5, Shelness teach the truncated scaffold protein can be optimized from 0.5% to 90% [0073]. Shelness further teaches apoB is capable of stabilizing the bilayer particle for controlling the size of the nanolipoprotein particle [0065, Fig 4]. Thus, the molar ratio of a scaffold protein in a nanolipoprotein bilayer particle is a result effective variable, which can be optimized through routine experimentation. MPEP 2144.05 (II) states “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).”
With respect to claim 7, Leigh et al. teach the lysolipid of MAPC is mono-acyl phosphatidyl choline (col 5, line 36-38), reading on lysophospholipids.
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With respect to claims 8-10, Leigh et al. suggest the phosphatidyl choline (PC) and monoacyl phosphatidyl choline (MAPC) are endogenous compounds (col 6, line 2-3). The common endogenous fatty acids are palmitate (linear C16) or myristic acid (linear C14) well-known in the art as evidenced by Zoac et al. (p567, col 1). Leigh's mono-acyl phosphatidyl choline (MAPC) reads on the compound formulas (I) and (Ia) shown above; wherein R1 is C13 or C15 alkyl. A lysolipid of myristic acid (R1=C13) reads on the elected species of l-tetradecanoyl-sn-glycero-3-phosphocholine (lyso 14:0).
With respect to claim 13, Shelness teaches truncated apoB as a fusion protein with a single chain antibody, ligand or receptor, or any other peptide sequence that would be specific for a particular macromolecular cell surface marker [0024]. Shelness teaches the use of truncated apoB to compartmentalize lipophilic drugs, such as paclitaxel in a nanolipoprotein particle [0018, Fig 2-4], reading on a functionalized amphipathic compound.
With respect to claim 25, Shelness in view of Leigh et al. teach a nanolipoprotein particle comprising a membrane forming lipid of phospholipids and lysolipids as well as a scaffold protein in a composition/system. Shelness teaches the system/composition comprising a membrane forming lipid of phospholipids and lysolipids [0054] as well as a scaffold protein [0058]. Shelness shows upon assembly the one or more membrane forming lipids and the scaffold protein provide a discoidal membrane lipid bilayer for the nanolipoprotein particle in which the one or more lysolipids are comprised within the discoidal membrane lipid bilayer in the system (Fig 4). Shelness shows the scaffold protein able to stabilize phospholipids and lysolipids in the system in figure 4 (known as nanodisk/ND) and further evidenced by Ryan’s teaching that the edge of ND is stabilized through apolipoprotein binding to the disk perimeter (p344, Fig 1, legend). Leigh et al. suggest that molar ratio of phosphatidylcholine (PC) to a lysophospholipid of mono-acyl phosphatidyl choline (MAPC) as an result effective variable and an optimized ratio of 60:40 can beneficially increase the amount of a delivered lipophilic drug carried by the nanolipoprotein particle (Fig 10) in the system. Leigh et al. further suggest a lysolipid of mono-acyl phosphatidyl choline (MAPC) in the system as reading on the compound formulas (I) and (Ia); wherein R1 is C13 or C15 alkyl. When R1=C13, Q1=Q2=O, n=1, 0=0, m=2, R21=H, and Z= choline. Leigh’s Lysolipid reads on the compound of l-tetradecanoyl-snglycero-3-phosphocholine (lyso14:0 with CPC of 80 µM as disclosed in the specification [00180]). Also See rejection of claim 1 above.
With respect to claim 34, see rejection of claim 1 above. Claim 34 has broader claim scope than the rejected claim 1 above.
With respect to claim 35, Leigh's mono-acyl phosphatidyl choline (MAPC) reads on the compound formulas (I) and (Ia) shown above; wherein R1 is C13 or C15 alkyl. A lysolipid of myristic acid (R1=C13) reads on the elected species of l-tetradecanoyl-sn-glycero-3-phosphocholine (lyso 14:0). See rejection of claims 8-10 above.
With respect to claim 36, Zhang et al. is cited to show common knowledge that lysolipids, e.g., lysophosphatidylcholine, having one hydrocarbon chain serves as surfactant in a lipid bilayer vesicle [0035-0036]. One of ordinary skill in the art would have known to optimize the amount of lysolipid in the nanolipoprotein particle (nanodisk) below critical micelle concentration of the lysolipid (CMC) to avoid micelle formation. Furthermore, Leigh’s Lysolipid reads on the elected compound of l-tetradecanoyl-snglycero-3-phosphocholine (lyso14:0) with CPC of 80 µM as disclosed in the specification [00180].
Response to Arguments
Applicant's arguments filed 11/15/2025 have been fully considered but they are not persuasive. See response to arguments above.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIA-HAI LEE whose telephone number is (571)270-1691. The examiner can normally be reached Mon-Fri from 9:00 AM to 6:00 PM.
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/J.L/Examiner, Art Unit 1658
26-December-2025
/LI N KOMATSU/ Primary Examiner, Art Unit 1658