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 .
Claims 1-3 and 6-35 are currently pending
Applicant's election with traverse of Group III in the reply filed on 05/26/2026 is acknowledged.
The traversal is on the ground(s) that the claims as amended involve a special technical feature that makes a contribution over the Agrahari paper cited in the Requirement for Restriction of 03/26/2026 based on Applicant’s assertion that the instant claimed inventions require galactosylated dendrimers comprising oligoethylene building blocks and the galactosylated dendrimers of Agrahari do not require oligoethylene building blocks. This is not found persuasive because the “special technical feature” described by Applicant does not link all claims of all groups as claimed by Applicant. Instant claim 22, even as amended, is directed to pharmaceutical formulations that may be used in the method of claim 1 and does not specifically require this pharmaceutical formulation to comprise galactosylated dendrimers comprising oliogoethylene building blocks.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-3, 6-21 and 23-28 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 05/26/2026.
Claims 22 and 29-35 will be examined on the merits.
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.
Claim(s) 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Patterson Veterinary Supply (Patterson Veterinary Supply; Saline Solution 0.9%; URL = https://www.pattersonvet.com/Supplies/fluids-iv-administration/iv-fluids/saline-solution-0-9/PIF_34296 ; First available 1/31/2001; Accessed 8/10/2026).
Note on claim interpretation: instant claim 22 is directed to a pharmaceutical formulation for use in the method of claim 1. The BRI for claim 22 encompasses any pharmaceutical composition that can be used in the method of claim 1. As such, claim 22 is being interpreted as encompassing pharmaceutical compositions that may be used as diluents for preparing the galactosylated dendrimer-comprising composition administered in the method of instant claim 1.
Patterson Veterinary Supply teaches of 0.9% sterile saline, which is isotonic with body fluids and uses as a diluent for antibiotics, other pharmaceuticals and biologics (Patterson Veterinary Supply, p1). In the instant case, the 0.9% sterile saline of Patterson Veterinary supply is a pharmaceutical formulation and could be used as a diluent for preparing the galactosylated dendrimer-comprising composition administered in the method of claim 1.
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.
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) 22 and 29-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agrahari (Agrahari, et al, RSC Adv, 2020, 10:31553) in view of Cloninger (Cloninger, et al., Curr. Opin. Chem. Biol. 2002 6:742), Sonoke (Sonoke, et al., Biol. Pharm. Bull 2011 34(8):1338), Sheikhi (Sheikhi, et al., Mater. Chem. Front. 2018 2(11): 2081).
Agrahari teaches on the subject of the syntheses of glycodendrimers with terminal galactose units using copper catalyzed azide-alkyne cycloaddition (Agrahari, Abstract). Agrahari teaches that both 1[Wingdings font/0xE0]2 branching dendrimers as well as 1[Wingdings font/0xE0]3 branching may be produced by the method of Agahari (Agahari, Abstract). Agrahari teaches that dendrimers that expand divergently in a 1[Wingdings font/0xE0]3 branching fashion have a significant advantage of dendrimers expanding in a 1[Wingdings font/0xE0]2 branching fashion due to its densely distributed peripheral groups for the same generation (Agrahari, p 31553, ¶ 1). Agrahari teaches a 1[Wingdings font/0xE0]2 branching generation 1 dendrimer, which comprises six terminal galactose groups (note: galactose groups have acyl protecting groups), deemed compound 20 of Agrahari:
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(Agrahari, Scheme 4, Compound 20)
…. as well as a 1[Wingdings font/0xE0] 2 branching generation 2 dendrimer comprising 12 terminal galactose groups, deemed compound 21 of Agrahari:
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(Agrahari, Scheme 4, Compound 21)
… as well as a 1[Wingdings font/0xE0]3 divergent branching generation 2 dendrimer comprising 18 terminal galactose units, deemed compound 22 of Agrahari:
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(Agrahari, Scheme 4, Compound 22).
Agrahari does not teach galactosylated dendrimers comprising galactose linked to tetraethylene glycol. Agrahari does not teach a generation 2 dendrimer comprising 6 internal galactose units connected throught TEG, 24 outer layer galactose moieties and 24 terminal hydroxyl groups. Agrahari does not teach that the galactosylated dendrimer comprises one or more therapeutic, diagnostic or prophylactic agents for delivery to the liver.
Cloninger teaches subject of biological applications of dendrimers (Cloninger, Abstract). Cloninger teaches that dendrimers are comprised of several different building block types including: A) poly(amidoamine) (PAMAM) building blocks, (Cloninger, p 742, ¶ 1; Fig. 1(a)), B) poly(propylene imine) building blocks (Cloninger, p 742, ¶ 1; Fig 1(b)), C) saccharide building blocks (Cloninger, p 742, ¶2; Fig 2(a)) and D) amino acid building blocks (Cloninger, p 743, ¶ 4; Fig. 2(b)), with the saccharide building block example of Cloninger being depicted below:
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(Cloninger, Fig. 2(a))
Cloninger also teaches that dendrimers as targeted delivery agents for the delivery of therapeutic agents encapsulated within the void space of the dendrimer (Cloninger, p 745, ¶ 2; Fig. 4(a)).
Sheikhi teaches on the subject of TEG-based dendrimers (Sheikhi, Abstract). Sheihi teaches that TEG was chosen as the branching unit due to its water solubility as well as the flexibility the TEG chains add to the dendrimer (Sheikhi, p 2983, ¶ 4). An example of a generation 2 TEG 1[Wingdings font/0xE0]3 branching dendrimer of Sheikhi:
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(Sheikhi, Scheme 3; Red arrows pointing to flexible, hydrophilic TEG groups added by examiner).
Sonoke teaches on the subject of galactose-modified cationic liposomes for delivery of siRNA to the liver (Sonoke, Abstract). Sonoke teaches that receptor-mediated drug targeting is a promising approach for delivering drugs to specific cell types, with hepatocytes comprising surface receptors that recognizes and facilitates their uptake (Sonoke, p 1338, ¶ 2). Sonoke teaches that cationic liposomes comprising terminal galactose units and comprising siRNA were able to enhance the transfer of the siRNA-comprising liposomes into hepatocytes in vivo (Sonoke, p 1338, ¶ 2).
It would be prima facie obvious to one of skill in the art to start with the 6 galactose-comprising dendrimer 20 of Agrahari:
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… and attach 4 galactose molecules via the TEG linker of Sheikhi to each of the six terminal galactose moieties of compound 20 of Agrahari via the 4 AcO groups present on the galactose units of compound 20 to form a G2 dendrimer comprising 6 internal galactose units linked to 24 outer galactose units via TEG and use the resultant G2 galactosylated dendrimer to deliver dendrimer-encapsulated therapeutic moieties to liver cells in view of the teachings of Sonoke, Agrahari, Sheikhi and Cloninger. One of ordinary skill in the art would be motivated to do this in order to better treat liver diseases. One of ordinary skill in the art would have a reasonable expectation of success attaching 4 galactose molecules via the PEG linker of Sheikhi to each of the six terminal galactose moieties of compound 20 of Agrahari via the 4 AcO groups present on the galactose units of compound 20 to form a G2 dendrimer comprising 6 internal galactose units linked to 24 outer galactose units via TEG and use the resultant G2 galactosylated dendrimer to deliver dendrimer-encapsulated therapeutic moieties to liver cells because: 1) Agrahari teaches that 1[Wingdings font/0xE0]3 branched dendrimers have a significant advantage over 1[Wingdings font/0xE0]2 branched dendrimers due to increased density of peripheral groups for the same generation, which would naturally lead one of skill in the art to explore higher branching degrees, including 1[Wingdings font/0xE0]4 as a means to further increase the density of peripheral galactose groups, 2) one of skill in the art, having read and understood both Agrahari and Cloninger would realize that the 6 galactose units present on compound 20 of Agrahari could be used as dendrimer building blocks themselves to generate such a 1[Wingdings font/0xE0]4 branched G2 dendrimer via the four oxygens on each of the galactose units, 3) Sheikhi teaches that addition of the TEG building block of Sheikhi would add both hydrophilicity and flexibility to the G2 dendrimer and 4) Sonoke teaches that galactose-terminated structures are capable of mediating delivery of therapeutic agents to liver cells via interaction of the terminal galactose moieties with surface enzymes on hepatocytes that bind and facilitate the uptake of galactose-comprising moieties.
Note: Regarding claim 30 specifically, there are 24 terminal galactose units in the G2 dendrimer of Agrahari, Sheikhi, Sonoke and Cloninger described above and each of these has four AcO groups, which become hydroxyls upon deprotection and 24 galactose * 4 OH/galactose = 96 terminal hydroxyls.
Claim(s) 22 and 29-34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agrahari (Agrahari, et al, RSC Adv, 2020, 10:31553) in view of Cloninger (Cloninger, et al., Curr. Opin. Chem. Biol. 2002 6:742), Sonoke (Sonoke, et al., Biol. Pharm. Bull 2011 34(8):1338), Sheikhi (Sheikhi, et al., Mater. Chem. Front. 2018 2(11): 2081) as applied to claims 22 and 29-32 above and in further view of Khoshbaten (Khoshbaten, et al., Hepat. Mon 2010 1:10(1):12).
The combined teachings of Agrahari, Cloninger, Sonoke and Sheikhi are discussed above.
The combined teachings of Agrahari, Cloninger, Sonoke and Sheikhi do not teach the G2 dendrimer comprising 24 terminal galactose units collectively taught by Agrahari, Cloninger, Sonoke and Sheikhi comprises a therapeutic agent that is the antioxidant N-acetyl cysteine (NAC).
Khoshbaten teaches on the subject of the antioxidant NAC as a treatment for nonalcoholic fatty liver disease (NAFLD) (Khoshbaten, Abstract). Khoshbaten teaches that the antioxidant NAC of Khoshbaten was able to improve liver function in patients with NAFLD (Khoshbaten, Conclusions).
It would be prima facie obvious to one of ordinary skill in the art to choose the NAC of Khoshbaten as the therapeutic agent encapsulated in the 24 terminal galactose-comprising, G2 dendrimer of Agrahari, Cloninger, Sonoke and Sheikhi and administer the resultant NAC-comprising dendrimer in methods of treating NAFLD. One of ordinary skill in the art would be motivated to do this to better treat NAFLD. One of ordinary skill in the art would have a reasonable expectation of success choosing the NAC of Khoshbaten as the therapeutic agent encapsulated in the 24 terminal galactose-comprising, G2 dendrimer of Agrahari, Cloninger, Sonoke and Sheikhi and administer the resultant NAC-comprising dendrimer in methods of treating NAFLD because the 24 terminal galactose-comprising, G2 dendrimer of Agrahari, Cloninger, Sonoke and Sheikhi is capable of delivery of therapeutic agents to liver cells and Khoshbaten teaches NAC can be used to treat nonalcoholic fatty liver disease.
Claim(s) 22, 29-32 and 34-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agrahari (Agrahari, et al, RSC Adv, 2020, 10:31553) in view of Cloninger (Cloninger, et al., Curr. Opin. Chem. Biol. 2002 6:742), Sonoke (Sonoke, et al., Biol. Pharm. Bull 2011 34(8):1338), Sheikhi (Sheikhi, et al., Mater. Chem. Front. 2018 2(11): 2081) as applied to claims 22 and 29-32 above and in further view of Hadi (Hadi, et al., Antioxidants 2018; 7, 12)
The combined teachings of Agrahari, Cloninger, Sonoke and Sheikhi are discussed above.
The combined teachings of Agrahari, Cloninger, Sonoke and Sheikhi do not teach the G2 dendrimer comprising 24 terminal galactose units collectively taught by Agrahari, Cloninger, Sonoke and Sheikhi comprises a therapeutic agent that is the antioxidant vitamin E.
Hadi teaches on the subject of the antioxidant Vitamin E as a therapeutic agent for NAFLD (Hadi, Abstract). Hadi teaches that clinical trials for NAFLD have showed modest improvement in liver biochemistry and histology induced by vitamin E administration (Hadi, p 8, ¶ 7-8).
It would be prima facie obvious to one of ordinary skill in the art to choose the vitamin E of Hadi as the therapeutic agent encapsulated in the 24 terminal galactose-comprising, G2 dendrimer of Agrahari, Cloninger, Sonoke and Sheikhi and administer the resultant vitamin E -comprising dendrimer in methods of treating NAFLD. One of ordinary skill in the art would be motivated to do this to better treat NAFLD. One of ordinary skill in the art would have a reasonable expectation of success choosing the vitamin E of Hadi as the therapeutic agent encapsulated in the 24 terminal galactose-comprising, G2 dendrimer of Agrahari, Cloninger, Sonoke and Sheikhi and administer the resultant vitamin E -comprising dendrimer in methods of treating NAFLD because the 24 terminal galactose-comprising, G2 dendrimer of Agrahari, Cloninger, Sonoke and Sheikhi is capable of delivery of therapeutic agents to liver cells and Hadi teaches vitamin E produces a modest improvement in liver biochemistry and histology in NAFLD clinical trials.
Conclusion
Claims 22 and 29-35 are rejected.
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sydney Van Druff whose telephone number is (571)272-2085. The examiner can normally be reached 10 am - 6 pm.
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/SYDNEY VAN DRUFF/ Examiner, Art Unit 1643
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643
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