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 .
Status of Claims
Claims 60-63 and 67-77 are pending as of the response and amendments filed on 8/18/26. Claims 1-59 and 64-66 have been canceled, claims 72-77 are currently withdrawn from examination as being directed to a non-elected invention. Claims 60-63 and 67-71 are currently under examination.
The rejection of claims 65-67 under 35 USC 112(b) is withdrawn in consideration of the amendments.
The 103 rejections of record over Bharatam, J. Nanosci. & Nanotech. Publ. 2006; over Kannan, US 20170119899; over Kannan in view of Still; over Kannan in view of Rangaramanujam; and over Kannan in view of Kobayashi are withdrawn in consideration of the amendments.
Based on the amendments, new rejections under 35 USC 103 are made, discussed below.
Claims 60-63 and 67-71 were examined and are rejected.
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) 60 and 67-71 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rangaramanujam et. al., US 20190142964 A1, publ. 5/16/2019, cited in an IDS.
Rangaramanujam teaches dendrimer formulations comprising one or more prophylactic or therapeutic agents, suitable for topical, enteral or parenteral delivery for treatment of various diseases (title & abstract; para [0004]). Rangaramanujam teaches the dendrimers to have a high density of hydroxy groups, at least 1 hydroxyl group/nm3, wherein the dendrimers have a central core; one or more branching units; and terminal functional groups (para [0014-0015]). Rangaramanujam teaches preferably the therapeutic agent is covalently conjugated to the dendrimer via one or more linkages selected from a disulfide, ester, ether, carbamate, carbonate, or amide group(s), optionally via one or more spacers (para [0017], [0069]). Rangaramanujam teaches the therapeutic agent to be a nucleic acid, small molecule, peptidomimetic, protein, peptide, carbohydrate, or lipid (para [0034], [0075]). Rangaramanujam teaches preferred active agents to include agents that promote peroxisome proliferation, e.g., agonists of PPAR, such as pioglitazone (para [0083]). The dendrimers are taught to include generations 4, 5 or 6 polyamidoamine (PAMAM) (para [0046]). Rangaramanujam exemplifies the following dendrimer for conjugation (p. 6, Formula I):
PNG
media_image1.png
200
400
media_image1.png
Greyscale
. Notably, the dendrimer has a plurality of terminal hydroxyl groups and linkers comprising PEG and triazolyl rings. Rangaramanujam teaches an embodiment wherein conjugation of the active agents/linkers occurs via about 1-5% of the total available hydroxyl groups of the dendrimers prior to the conjugation (para [0146]). Rangaramanujam teaches the dendrimers as biocompatible and inexpensive, and to allow for improved delivery to the CNS (para [0010-0011], [0013]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims, to have arrived at the composition of the instant claims, comprising a dendrimer conjugated to a PPAR agonist, such as pioglitazone, through a linker comprising PEG and triazolyl rings, wherein the dendrimer has a plurality of terminal hydroxyl groups, and wherein an ether linkage is formed by a terminal group of the dendrimer conjugated to the linker in consideration of Rangaramanujam. Rangaramanujam teaches dendrimer formulations comprising one or more prophylactic or therapeutic agents including PPAR agonists such as pioglitazone, conjugated via a linker to the dendrimer, wherein the dendrimer formulations are biocompatible and inexpensive, and allow for improved delivery to the CNS. Rangaramanujam exemplifies a dendrimer has a plurality of terminal hydroxyl groups and linkers comprising PEG and triazolyl rings, as well as the therapeutic agent being conjugated to the dendrimer via one or more linkages selected from a disulfide, ester, ether, carbamate, carbonate, or amide group(s), optionally via one or more spacers. As such, one of ordinary skill in the art would have found it prima facie obvious to have arrived at the composition of the instant claims and have had a reasonable expectation of success.
Claim(s) 61 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rangaramanujam et. al., US 20190142964 A1, as applied to claims 60 and 67-71 above, in view of Kannan et. al., US 20170119899 A1, publ. 5/4/2017, of previous record.
The teachings of Rangaramanujam as discussed previously are incorporated herein. Additionally, Rangaramanujam teaches the dendrimers are intact after clearance through the kidneys (para [0040]). However, kits are not explicitly taught.
Kannan teaches compositions comprising dendrimers conjugated with a therapeutic agent (title & abstract; para [0012]). Kannan teaches dendrimers for conjugation to include PAMAM dendrimers, for conjugation to therapeutic agents such as pioglitazone (para [0013]). Kannan teaches the compositions to have therapeutic utility for treating peroxisomal disorders, including cystic kidneys (para [0151]). Kannan further teaches medical kits for the dendrimer compositions, optionally including pharmaceutical carriers, in dosage units in one or more containers, with instructions for administration (para [0173]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims, to have incorporated the dendrimer composition of Rangaramanujam into a medical kit as described by Kannan. Rangaramanujam and Kannan both teach dendrimer compositions comprising therapeutic agents such as pioglitazone, while Kannan teaches such compositions as therapeutically useful for treating cystic kidneys, and that these compositions can conveniently be incorporated into a medical kit with instructions for administration. As such, one of ordinary skill in the art would have been motivated to have incorporated the dendrimer composition of Rangaramanujam into a medical kit with instructions for administration, such as for treating cystic kidneys, and have had a reasonable expectation of success.
Claim(s) 62 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rangaramanujam et. al., US 20190142964 A1, as applied to claims 60 and 67-71 above, in view of Still et. al., Calcif. Tissue Int., vol. 83, pp. 285-292, publ. 2008, of previous record.
The disclosure of Rangaramanujam as discussed previously is incorporated herein. In addition to pioglitazone as a therapeutic agent for conjugation to a dendrimer, bezafibrate is included as an acceptable therapeutic (para [0083]).
Rangaramanujam doesn’t explicitly teach the therapeutic agent as a PPAR-δ agonist.
Still teaches bezafibrate as a PPARα/δ agonist (abstract).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the conjugate composition of the instant claims, comprising the PPARα/δ agonist, bezafibrate, covalently conjugated through a linker comprising PEG and triazolyl rings, wherein the dendrimer has a plurality of terminal hydroxyl groups, and wherein an ether linkage is formed by a terminal group of the dendrimer conjugated to the linker. As discussed previously, Rangaramanujam teaches dendrimer formulations comprising one or more prophylactic or therapeutic agents, such as pioglitazone and bezafibrate, conjugated to the dendrimer via a linker, while Still teaches bezafibrate as a PPARα/δ agonist. Therefore, one of ordinary skill in the art would have found it prima facie obvious to have arrived at the dendrimer composition of the instant claims comprising a PPAR-δ agonist, bezafibrate, covalently conjugated to a dendrimer as described in Rangaramanujam, and have had a reasonable expectation of success.
Claim(s) 62-63 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rangaramanujam et. al., US 20190142964 A1, as applied to claims 60 and 67-71 above, in view of Kobayashi et. al., WO 2010110479, publ. 9/30/2010, of previous record.
The disclosure of Rangaramanujam as discussed previously is incorporated herein. However, indanyl acetic acid derivatives that are PPAR-δ agonist are not explicitly taught.
Kobayashi teaches indanylacetic acid derivative compounds as PPAR activators for the treatment of PPAR-mediated diseases (abstract; para [0001], [0003]). In particular, Kobayashi teaches the compounds as PPARδ agonists, with some compounds also possessing PPARα and/or PPARγ agonist activity, and that these agents have therapeutic utility for treating a variety of conditions such as malignant tumors, diabetes, obesity, hypercholesterolemia, heart failure, cardiovascular disease, Alzheimer’s disease and other neurodegenerative diseases, and other inflammatory diseases (p. 12 of 26; p. 24 of 26, Table 13; p. 26 of 26, claim 15).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the composition of the instant claims comprising a dendrimer having a plurality of terminal hydroxyl groups conjugated to a PPARδ agonist, an indanylacetic acid derivative, wherein the conjugation is via an ester or amide linkage in consideration of the combined teachings of Rangaramanujam and Kobayashi.
As discussed previously, Rangaramanujam teaches dendrimer formulations comprising one or more prophylactic or therapeutic agents, including PPAR agonists such as pioglitazone and bezafibrate, conjugated to the dendrimer via a linker. Kobayashi teaches indanylacetic acid derivative compounds as PPAR agonists, wherein the PPAR agonists are in particular PPARδ agonists, and that these agents have utility for treating neurodegenerative and inflammatory diseases. As such, one of ordinary skill in the art would have been motivated to have conjugated the indanyl acetic acid derivatives of Kobayashi to the dendrimers taught by Rangaramanuam, and have had a reasonable expectation of success.
Information Disclosure Statement
The IDS filed on 8/18/26 has been considered.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/ Primary Examiner, Art Unit 1627
