DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Request for Continued Examination (RCE), Amendments and Remarks, filed 28 August 2026, in the matter of Application N° 18/222,775. Said documents have been entered on the record. The Examiner further acknowledges the following:
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 28 August 2026 has been entered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 2 and 3 have been canceled. No claims have been added.
Claims 1, 11, and 17-20 have been amended. Independent claims 1 and 17 have been notably amended to recite that the triblock copolymer nanoparticles comprise conjugated folate with rapamycin. Both claims additionally recite that the nanoparticles are formulated to provide polycystic kidney disease-targeted delivery by accumulating in the polycystic kidney disease-affected tissue and cystic tubular epithelium. The amended limitations are supported.
Claims 11, 18, and 19 are editorially amended and claim 20 is narrowed to recite a kidney as the targeted organ.
No new matter has been added.
Thus, claims 1, 4-6, and 8-20 now represent all claims currently under consideration.
Information Disclosure Statement
No new Information Disclosure Statement(s) (IDS) have been filed for consideration.
Withdrawn Rejections
Rejection under 35 USC 103
Applicants’ amendment to claim 1 is sufficient in overcoming the previously maintained obviousness rejection over Zhang. As amended, the nanoparticles now comprise rapamycin that is conjugated to folate, a limitation which is not met by the reference. As such, the rejection is withdrawn.
Rejection under 35 USC 103
Applicants’ remarks traversing the combined teachings of Zhang and Kipp are adequate in overcoming the previously maintained obviousness rejection. As such, the rejection is withdrawn.
Rejection under 35 USC 103
Applicants’ remarks traversing the combined teachings of Zhang, Kipp, and Knight are adequate in overcoming the previously maintained obviousness rejection. As such, the rejection is withdrawn.
New Rejections
Applicants’ amendments have necessitated the following ground(s) of rejection:
Claim Rejections - 35 USC §112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10 and 11 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As amended, claim 1 now recites that the nanoparticles “comprise conjugated folate with rapamycin” (i.e., folate-conjugated rapamycin). Claim 10 continues to recite “wherein the one or more pharmaceutical agents are conjugated to folate, while claim 11 similarly recites “wherein one of the one or more pharmaceutical agents is conjugated to folate.”
As claim 1 now requires at least one folate-conjugated pharmaceutical agent in rapamycin, the dependent claims are not considered to further limit the claim from which they both depend.
Applicants may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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. Applicants are 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.
Claims 1, 4-6, 8, 10-16, and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (ACS Biomater. Sci. Eng.; 2019).
As amended, the limitations recited by instant claim 1 are directed to a nanoparticle formulation comprising one or more pharmaceutical agents encapsulated in a polymer, wherein the polymer is a triblock copolymer and the nanoparticles comprise conjugated folate with rapamycin. The limitation reciting “conjugated folate with rapamycin” is broadly and reasonably considered as reciting folate-conjugated rapamycin.
The limitations reciting that the nanoparticulate formulations are “for the treatment of chronic kidney diseases” remains drawn to one of intended use. Similarly, the final limitation reciting that the nanoparticles “are formulated to provide polycystic kidney disease-targeted delivery by accumulating in polycystic kidney disease-affected tissue and cystic tubular epithelium” is broadly and reasonably considered as also being directed to a recitation of intended use. The “formulated” limitation does not add any compositional or structural limits to the composition of the claim.
Huang discloses a folate receptor-mediated renal-targeting nanoplatform for the specific delivery of an active agent in order to treat renal ischemia/reperfusion (see e.g., Title; Abstract).
The Examiner acknowledges that the article is deficient insomuch as it exemplifies triptolide as the delivered active agent (see e.g., Abstract).
However, the article more generally, is directed to developing renal-targeting Pluronic F127/P123 nanoparticles (FPNPs) as a delivery platform of drugs for treating renal diseases (see Abstract).
Huang additionally teaches that in normal tissues and organs, folate receptor (FR) usually expresses in kidney membranes (see pg. 2878, left col., lines 2-4). Several FRs can specifically express in renal proximal tubule epithelial cells (PTECs) as well as [have a] high affinity between folate (FA) and FR, thus resulting in FA-modified vehicles being able to deliver drugs to the kidney by FR-mediated endocytosis.
The teachings of Shillingford and Taylor are incorporated by reference in their discussion of their respective teachings (see pg. 2878, left col., lines 9-13).
Therein it is respectively disclosed that “Shillingford and his co-workers have demonstrated that FA-rapamycin conjugate could achieve kidney-targeting delivery by FR-mediated endocytosis,” while “Taylor’s group also created a 4-hydroxy-Tempo-FA to target PTECs for preventing renal IRI.”
Huang further acknowledges that “[a]lthough drug-FA conjugates can achieve kidney targeting, they still have some deficiencies such as short retention time in blood circulation and inefficient drug release” and advance that drug nanocarriers (e.g., polymeric) possess superiority in prolonging drug retention time and improving drug release efficiency in vivo.
To accomplish this, Pluronic copolymers are used as biocompatible and easily modified nanocarriers which can form a core-shell structure to incorporate lipophilic drugs. Pluronics have shown great advantages in drug loading and controlled release drug carriers (see pg. 2878, left col.).
Combining the advantages of both folate conjugation and Pluronic copolymers, Huang constructed a biocompatible and high-efficiency renal-targeting platform, in this case for renal IRI therapy.
The foregoing disclosures are considered to teach the limitations of claims 1, 4-6, 8-14, and 17-20.
Regarding the dosing frequencies of claims 15 and 16, Huang discloses in the in vivo toxicological evaluation that the test subjects were injected with the composition of a test group three times per week for three weeks, thereby receiving their designated dose less frequently than daily, but on a weekly basis (see pg. 2879, right col.).
Based on the foregoing combined teachings within the four corners of Huang, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited methods of treatment.
As established, Huang discloses a triblock, copolymer nanocarrier delivery platform that carries folate-conjugated drugs with the goal of extending their residency within the circulatory system and controlling their release at the intended target. The Examiner has acknowledged that the reference’s exemplified drug is a drug that is different from either of the drugs claimed, namely triptolide.
However, despite this more specific teaching, the Examiner also points out the incorporated disclosures of Shillingford and Taylor whereby both folate-conjugated rapamycin and folate-conjugated, 4-hydroxy-Tempo are discussed as being conjugated to target specific renal delivery points and conditions. The latter teaches targeting and preventing IRI, while the former teaches targeting the kidney to treat polycystic kidney disease.
Huang’s added disclosure of using Pluronic copolymers as nanocarriers to extend and control the delivery of the active of choice, the Examiner respectfully submits that a person of skill in the art before the effective filing date, would have expected to achieve the claimed compositions and methods
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (ACS Biomater. Sci. Eng.; 2019) as applied to claims 1 and 8, further in view of Yu et al. (Molecules; 2021).
As amended, the limitations recited by instant claim 1 are directed to a nanoparticle formulation comprising one or more pharmaceutical agents encapsulated in a polymer, wherein the polymer is a triblock copolymer and the nanoparticles comprise conjugated folate with rapamycin. The limitation reciting “conjugated folate with rapamycin” is broadly and reasonably considered as reciting folate-conjugated rapamycin.
The limitations reciting that the nanoparticulate formulations are “for the treatment of chronic kidney diseases” remains drawn to one of intended use. Similarly, the final limitation reciting that the nanoparticles “are formulated to provide polycystic kidney disease-targeted delivery by accumulating in polycystic kidney disease-affected tissue and cystic tubular epithelium” is broadly and reasonably considered as also being directed to a recitation of intended use. The “formulated” limitation does not add any compositional or structural limits to the composition of the claim.
Huang discloses a folate receptor-mediated renal-targeting nanoplatform for the specific delivery of an active agent in order to treat renal ischemia/reperfusion (see e.g., Title; Abstract).
The Examiner acknowledges that the article is deficient insomuch as it exemplifies triptolide as the delivered active agent (see e.g., Abstract).
However, the article more generally, is directed to developing renal-targeting Pluronic F127/P123 nanoparticles (FPNPs) as a delivery platform of drugs for treating renal diseases (see Abstract).
Huang additionally teaches that in normal tissues and organs, folate receptor (FR) usually expresses in kidney membranes (see pg. 2878, left col., lines 2-4). Several FRs can specifically express in renal proximal tubule epithelial cells (PTECs) as well as [have a] high affinity between folate (FA) and FR, thus resulting in FA-modified vehicles being able to deliver drugs to the kidney by FR-mediated endocytosis.
The teachings of Shillingford and Taylor are incorporated by reference in their discussion of their respective teachings (see pg. 2878, left col., lines 9-13).
Such is considered to teach the limitations recited by instant claims 1 and 8.
Where Huang is deficient is with respect to instant claim 9 which narrows the poloxamer of claim 8, to poloxamer 188 (aka Pluronic F-68).
Yu bridges this gap in teaching in its discussion of Pluronic polymers. The Examiner acknowledges that the article additionally discusses the use of Pluronics for the delivery of cancer/tumor treatments and this diverges from the instant invention and the teachings of Huang. However, Yu is being relied upon for its teachings of the delivery polymer.
Therein, Yu discusses classification of the different Pluronic polymers correlating their hydrophilic-lipophilic balance (HLB) with the length of the middle PPO chain. Figure 2 (pg. 3 of 23) depicts the core structure of Pluronic polymers as well as different blends and their defining chain lengths:
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The four different categories (I)-(IV) of polymers are categorized by their HLB ranges with category (I) having a HLB range of 20-29 and category (IV) having a HLB <20.
Here, it is reiterated that Huang discloses studying a blend of F127/P123, which according to the above classification scheme is a blend of categories (I) and (IV). Thus, what the above chart suggests to the ordinarily skilled artisan is that success in achieving the composition of instant claim 9 would have been expected in view of the teaching that F68 and F127 Pluronic polymers are similarly classified in terms of their HLB.
Section 2.1 of the reference discusses the first class of Pluronic polymers again noting its inclusion of both F68 and F127 and further defining the class as having good hydrophilicity, and excellent biocompatibility. These properties are recognized as being beneficial for the accumulation of drugs in an organism and the prolongation of the blood circulation time.
The article additionally characterizes F68 as being useful to enhance the stability of nanoparticles and premature drug leakage with the PEG chain having the effect of increasing stability and prolonging blood circulation (see paragraph bridging pp. 7-8).
MPEP §2144.06(II) states that “[i]n order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on Applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents.”
Based on the foregoing disclosure pertaining to the characterization of F68 and F127 blends of Pluronic, the Examiner submits that a person of ordinary skill in the art, practicing the method disclosed by Huang, would have reasonably expected success in producing the composition recited by instant claim 9 by substituting F68 for F127 in the blend used by Huang.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
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