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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a provisional application filed as 63/170,119 on 04/02/2021.
All claims are given the priority date of 04/02/2021.
Application Status
Receipt is acknowledged of amendment, filed 06/30/2026. Claims 1-6, 14-18, 22-24, 27-29 and 46-48 are currently pending.
Election/Restriction
Applicant’s election of Group I, drawn to claims 1-6, 14-18, 22-24 and 27-29 in the reply filed on 06/30/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant's election with traverse of the dendron of formula 1f in the reply filed on 06/30/2026 is acknowledged. However, no election-of-species requirement was made in the previous Office Action mailed on 05/04/2026. Accordingly, the traversal of an election-of-species requirement is moot due to requirement being made in the previous Office Action. Therefore, the current claim limitations will be examined as written.
Claims 46-48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/30/2026.
Claims 1-6, 14-18, 22-24 and 27-29 are currently under examination.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statements filed on 10/02/2023, 04/04/2025 and 04/13/2026 have been received and all references have been considered.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al (ACS Appl. Mater. Interfaces 13 May 2020; 12 (19): 21270–21282).
Regarding claim 1, Chen teaches dendrons were synthesized by the repetitive condensation of a difunctional alcohol with acetonide-protected (2,2-bis (hydroxymethyl) propionic acid (bis-MPA), followed by deprotection of the acetonide group, according to precedent (Page 21272, Column 1 bridging Column 2). Chen teaches that after building these polyesters to the desired dendron generation, we converted the alcohol functional groups of the dendron surface into primary amines by coupling to Boc-protected β-alanine, followed by TFA deprotection, which ultimately yielded the desired polycationic target structures (Page 21272, Column 2). Chen teaches the structure of instant formula Ic wherein eight amine groups are attached to a C8G3 polyester dendron and hydrophobic unit (Page 21270, Abstract and Page 21272, Figure 1) as shown below:
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Regarding claim 2, Chen teaches the structure of instant formula Ic wherein eight amine groups are attached to a C8G3 polyester dendron and hydrophobic unit (Page 21270, Abstract and Page 21272, Figure 1).
Regarding claim 3, Chen teaches dendrons were synthesized by the repetitive condensation of a difunctional alcohol with acetonide-protected (2,2-bis (hydroxymethyl) propionic acid (bis-MPA), followed by deprotection of the acetonide group, according to precedent (Page 21272, Column 1 bridging Column 2). Chen teaches that after building these polyesters to the desired dendron generation, we converted the alcohol functional groups of the dendron surface into primary amines by coupling to Boc-protected β-alanine, followed by TFA deprotection, which ultimately yielded the desired polycationic target structures (Page 21272, Column 2). Chen teaches the structure of instant formula Ic wherein eight amine groups are attached to a C8G3 polyester dendron and hydrophobic unit (Page 21270, Abstract and Page 21272, Figure 1).
Regarding claim 4, Chen teaches the polyester dendron is an eight branched dendron (Page 21270, Abstract and Page 21272, Figure 1).
Regarding claim 5, Chen teaches eight amine end groups wherein the amine group is N, N-dimethylmethanamine (Page 21271, Scheme 2 and Page 21272, Column 1 and Figure 1).
Regarding claim 6, Chen teaches the structure of instant formula Ic wherein eight amine groups are attached to a C8G3 polyester dendron and hydrophobic unit (Page 21270, Abstract and Page 21272, Figure 1).
Claims 1-4 and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Poon et al (Nanomedicine: Nanotechnology, Biology, and Medicine 7 (2011) 201-209).
Regarding claim 1, Poon teaches paclitaxel encapsulated LDP micelles wherein the LDP is a fully biodegradable chemical composition comprising the polyester bis-MPA dendron core, hydrophobic COOH-PEG-OOC unit and NH2+ amine end groups that is functionalized with folate (Page 203, Figure 1A and Column 2).
Regarding claims 2 and 3, Poon teaches the polyester bis-MPA dendron is a G3, or generation 3, dendron core (Page 203, Figure 1A).
Regarding claim 4, Poon teaches the polyester bis-MPA dendron is a G3, or generation 3, dendron core and comprises 8 branches from the dendron core (Page 203, Figure 1A).
Regarding claims 14-17, Poon teaches paclitaxel encapsulated LDP micelles wherein the LDP is a fully biodegradable chemical composition comprising the polyester bis-MPA dendron core, hydrophobic COOH-PEG-OOC unit and NH2+ amine end groups that is functionalized with folate (Page 203, Figure 1A and Column 2). Poon teaches the use of the paclitaxel encapsulated LDP micelles conjugated with folate for the treatment of KB tumors (Page 208, Column 1 bridging Column 2).
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.
Claims 18, 22-24 and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Poon et al (Nanomedicine: Nanotechnology, Biology, and Medicine 7 (2011) 201-209) in view of Dohmen et al (WO 2015/128030 A1).
The teachings of Poon as described and applied above.
Regarding claims 18, 22, 24 and 27, Poon does not teach the nanoparticle composition further comprising a PEG-lipid wherein the PEG-lipid is 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (poly- ethylene glycol)- 2000] or 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000; wherein the composition comprises a phospholipid and cholesterol; and wherein the phospholipid is 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or distearoylphosphatidylcholine (DSPC).
Dohmen teaches dendrons comprising a core, branches and end/terminal groups wherein the core of the dendron to its periphery defines its generation (G-1, G-2, G-3); dendrimers of higher generations are larger, more branched and have more end groups at their periphery than dendrimers of lower generations (Page 40, Last paragraph bridging Page 41, first paragraph). Dohmen teaches the formula comprised in a nanoparticle (Page 9, Paragraph 1) further comprises lipids such as Cholesterol, DSPC and DMG-PEG2k (1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000) or DGP-PEG2k (1,2-dipalmitoyl-sn-glycerol methoxypolyethylene glycol-200) which are preferred helper lipids useful for preparing lipoplexes specifically for delivery of RNA (Page 56, last paragraph bridging Page 57, first paragraph). Dohmen teaches specifically the lipidoid C12-(2-3-2) was formulated with 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), cholesterol and 1,2-dipalmitoyl-sn-glycerol methoxypolyethylene glycol (DPG-PEG 2000) and loaded into nanoparticles which resulted in mRNA effectively expressed in the GI tract of rats and not detected in other major organs (Page 119, Paragraph 3; and Page 121, Results (last) paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Poon to include the specific PEG-lipid helper lipids as taught by Dohmen because Poon teaches it is within the ordinary skill in the art to use paclitaxel encapsulated LDP micelles wherein the LDP is a fully biodegradable chemical composition comprising the polyester bis-MPA dendron core, hydrophobic COOH-PEG-OOC unit and NH2+ amine end groups that is functionalized with folate to be delivered as a pharmaceutical composition for the treatment of KB tumors and Dohmen teaches lipidoid C12-(2-3-2) was formulated with 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), cholesterol and 1,2-dipalmitoyl-sn-glycerol methoxypolyethylene glycol (DPG-PEG 2000) and loaded into nanoparticles which resulted in mRNA effectively expressed in the GI tract of rats and not detected in other major organs.
One would have been motivated to make such a modification in order to receive the expected benefit of targeted delivery of mRNA using helper lipids as taught by Dohmen.
Regarding claims 23, 28 and 29, Poon does not teach the nanoparticle composition comprises the PEG-lipid in a range from 1 mol% to 10 mol% of the PEG-lipid per nanoparticle composition; the nanoparticle composition comprises the phospholipid in a range from 10 mol% to 15 mol% of the phospholipid per nanoparticle composition; and the nanoparticle composition comprises the cholesterol or derivative thereof in a range from 50 mol% to 75 mol% of the cholesterol or derivative thereof per nanoparticle composition.
Dohmen teaches that the dendron nanoparticle composition containing a lipidoid is about 40-60% lipidoid, about 40-60 % cholesterol, and about 5-20% PEG-lipid (in percent by weight, based on the total weight of the composition) (Page 56, last paragraph bridging Page 57, first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Poon to include the specific PEG-lipid helper lipids as taught by Dohmen because Poon teaches it is within the ordinary skill in the art to use paclitaxel encapsulated LDP micelles wherein the LDP is a fully biodegradable chemical composition comprising the polyester bis-MPA dendron core, hydrophobic COOH-PEG-OOC unit and NH2+ amine end groups that is functionalized with folate to be delivered as a pharmaceutical composition for the treatment of KB tumors and Dohmen teaches lipidoid C12-(2-3-2) was formulated with 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), cholesterol and 1,2-dipalmitoyl-sn-glycerol methoxypolyethylene glycol (DPG-PEG 2000) wherein the dendron nanoparticle composition containing a lipidoid is about 40-60% lipidoid, about 40-60 % cholesterol, and about 5-20% PEG-lipid (in percent by weight, based on the total weight of the composition).
One would have been motivated to make such a modification in order to receive the expected benefit of targeted delivery of mRNA using helper lipids as taught by Dohmen.
Pertinent Prior Art
The prior art Pearson et al (CS Macro Lett. 2013 Jan 15;2(1):77-81) is put on the record for teaching PCL3.5K-G3-PEG2K-NH2 dendrons within micelles for prospective drug delivery (Page 78, Scheme 1 and Page 2, Paragraph 2 of the supplemental information).
The prior art Hsu et al (Macromolecules. 2014 Oct 14;47(19):6911-6918) is put on the record for teaching a nucleic acid carrier comprising an alkyne-core functionalized polyester G3 dendron (870 g/mol) was conjugated with azido-functionalized PCL (3500 g/mol) using click chemistry, followed by PEGylation of the dendritic arms using heterobifunctional NH2-PEG600-BOC wherein the end groups of the PDCs were then modified to amine (PDC600-NH2) (Page 6913, Column 2 and Page 6914, Fig. 1A). Hsu teaches a series of PEGylated dendron-based micelles with various end groups (-NH2, -Ac, and -COOH) and PEG chain lengths (600 and 2000 g/mol) are prepared and tested in vitro (Page 6911, Abstract). Hsu teaches the micelles were prepared using the inclusion of rhodamine-labeled polymer or hydrophobic dyes in polymer solution (Page 6912, Column 2).
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
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