FINAL 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 .
Status of the Claims
This action is in response to papers filed 02/11/2026 in which claims 2, 11, 23-24, 36-37, and 40-59 were canceled; claims 4-5, 32-35, 38, and 39 were withdrawn; and claims 1, 3, 6-10, 16, 18, 25, and 26 were amended. All the amendments have been thoroughly reviewed and entered.
Claims 1, 3, 6-10, 12-22, and 25-31 are under examination.
Withdrawn Objections/Rejections
The Examiner has re-weighted all the evidence of record. Any rejection and/or objection not specifically addressed below is hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
New Objection
Claim Objections
Claim 16 is objected to because of the following informalities: the recitation of “selected from the group consisting of” followed by “including” is an improper Markush language. When materials recited in a claim are so related as to constitute a proper Markush groups, they may be recited in the conventional manner, or alternatively. For example, if “wherein R is a material selected from the group consisting of A, B, C and D” is a proper limitation, then “wherein R is A, B, C or D” shall also be considered proper. Appropriate correction is required.
New Rejections
Necessitated by Applicant’s Claim Amendments
Claim Rejections - 35 USC § 112 – NEW MATTER
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 21 and 22 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.
Claims 21 and 22 introduce new matter as the claims recite the limitations: “the oral delivery carrier includes an enteric coating and/or gelatin (claim 21) and “the oral delivery carrier is an enteric coating that includes a component selected from the group consisting of cellulose acetate, hydroxypropyl methyl cellulose, methyl acrylate, and combinations thereof” (claim 22). There is no support in the specification for the oral delivery carrier to include both “crosslinked chitosan” and “an enteric coating and/or gelatin” or in other words a combination of “crosslinked chitosan” and “an enteric coating and/or gelatin.”
Paragraph [0124] of the specification discloses “the oral delivery carrier can include an enteric coating and/or materials such as gelatin. Examples of enteric coatings include, but are not limited to, cellulose acetate, hydroxypropyl methyl cellulose, methyl acrylate, or combinations thereof.” While Paragraph [0124] later also discloses “[a]n a variation, the oral delivery carrier includes chitosan, and in particular, a nano-sized chitosan nanoparticle capsule (i.e., a nano-sized chitosan particle) that encapsulates the pharmaceutical payload. In a refinement, the chitosan capsule includes crosslinked chitosan,” these two embodiments (e.g., “enteric coating and/or materials such as gelatin” and “crosslinked chitosan”) are separate embodiments or “variation” of oral delivery carriers that are not indicated as used together or in combination. In other words, paragraph [0124] of specification only provide support for the oral delivery carrier to include either “an enteric coating and/or gelatin” OR “crosslinked chitosan.” However, claims 21 and 22 encompassed a combination of “crosslinked chitosan” and “an enteric coating and/or gelatin,” which is not supported by the specification. Thus, Applicant does not have possession of a combination of “crosslinked chitosan” and “an enteric coating and/or gelatin” as the oral delivery carrier.
MPEP §2163.06 states: “Applicant should therefore specifically point out the support for any amendments made to the disclosure.” Applicant has not directed the Examiner to the support in the specification for the amendment.
As such, the disclosure does not reasonably convey that the inventor had possession of the subject matter as amended at the time of filing of the instant application.
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.
Claim 10 is 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.
Claim 10 is not further limiting from claim 1 because claim 10 recites “polyethylene having a weight average molecular weight from about 500 Daltons to 10000 Daltons,” and thus, claim 10 has broadened from the scope of “polyethylene glycol having a weight average molecular weight less than or equal to 1800 Daltons” as recited in claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Modified Rejections
Necessitated by Applicant’s Claim Amendments
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 17 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 17, the recitation of “another statin” renders claim 17 indefinite because the metes and bounds of “another statin” is unclear. It is noted that claim 17 is dependent from claim 1, and claim 1 does not contain a statin as a the pharmaceutical payload and thus, it unclear what is meant and what is encompassed by “another statin.” It is suggested that the term “another” be removed, such that claim 17 recites the Markush group of “a pravastastin, a statin, or combinations thereof,” or claim 17 can also be amended to “a pravastastin, a statin other than pravastastin, or combinations thereof.”
As a result, claim 17 does not clearly set forth the metes and bounds of patent protection desired.
Response to Arguments
Applicant’s response filed 02/11/2026 did not address or amend claim 17 to address the 35 U.S.C. 112(b) indefinite rejection of claim 17.
Accordingly, claim 17 remained rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, for the reason of record.
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.
Claim(s) 1, 3, 6-10, 12-18, 21-22, 25, and 27-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (Nano Research, 2018, 11(10): 5584-5595; cited in ISR filed 11/11/2022) in view of Perumal et al( US 2012/0219600 A1; previously cited), Sosin et al (US 2016/0113881 A1), and Wang et al (WO 2019/128608 A1; English translation and citation via EPO; hereafter as “WO ‘608”).
Applicant elected targeting peptide sequence 6 as the species of kidney targeting peptide.
Regarding claim 1, Wang teaches a renal drug delivery system comprising nanoparticles formulation containing micelles comprising a hydrophobic core and a hydrophilic corona containing a kidney targeting peptide such as Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid)3-lysine) ((KKEEE)3K), wherein the micelles further contains a therapeutic agent (Abstract; pages 5585-5590). Wang teaches the kidney targeting peptide is conjugated to the hydrophobic core via a PEG linking compound (pages 5585-5587).
While Wang does not teach the delivery system contains an oral delivery carrier, it would have been obvious to disperse the micelles in a carrier that is suitable for oral administration/delivery in view of the guidance from Perumal.
Perumal teaches a drug delivery system comprising micelles dispersed in an oral pharmaceutically acceptable carrier so that the micelles can be suitable for oral delivery ([0006]-[0040], [0136]-[0156], and [0173]-[0174]).
It would have been obvious to one of ordinary skill in the art to disperse the micelles of Wang in an oral pharmaceutically acceptable carrier, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Perumal provided the guidance to do so by teaching that micelles can be dispersed in an oral pharmaceutically acceptable carrier so that the micelles can be suitable for oral administration/delivery. Thus, an ordinary artisan would have looked to formulating the micelles of Wang in conventionally known oral pharmaceutically acceptable carrier so that the micelles can be delivered orally, and achieve Applicant’s claimed invention with reasonable expectation of success.
With respect to the crosslinked chitosan of claim 1, Sosin teaches a nanoparticle composition in the form of micelles, wherein the micelle is an amphiphilic micelle which encapsulate therapeutic agents, wherein the nanoparticle composition is formulated for oral administration containing a carrier that include an enteric coating such as cellulose acetate, gelatin, or chitosan (Abstract; [0008], [0061]-[0110], [0199]-[0200], [0207]-[0214], [0135]). Sosin teaches the chitosan is crosslinked with tripolyphosphate ([0135]). Sosin teaches the use of enteric coating such as cellulose acetate or polymer such as chitosan crosslinked with tripolyphosphate, provides a drug delivery system which provides controlled release of the therapeutic agent ([0008]).
It would have been obvious to one of ordinary skill in the art to incorporate a chitosan crosslinked with tripolyphosphate as the oral pharmaceutically acceptable carrier that is used for formulating the drug delivery system of Wang in view of Perumal, and produce the claimed invention. One of ordinary skill in the art would have been motivated do so because Sosin provided the guidance to do so by teaching that polymer such as chitosan crosslinked with tripolyphosphate is a suitable material as carrier for formulating an oral drug delivery system so as provide a controlled release drug delivery system. Thus, an ordinary artisan looking to formulate a controlled release drug delivery system would have looked to incorporating a chitosan crosslinked with tripolyphosphate as the oral pharmaceutically acceptable carrier that is used for formulating the drug delivery system of Wang in view of Perumal, and achieve Applicant’s claimed invention with reasonable expectation of success.
With respect to the polyethylene glycol having a weight average molecular weight less than or equal to 1800 Daltons of claim 1, WO ‘608 teaches an amphiphilic mixed micelle having a hydrophobic core and a hydrophilic corona, wherein the micelle contains amphiphilic copolymer such as DSPE-PEG, wherein suitable PEGs include PEG having an average molecular weight of 1000 and 2000 (pages 1-2 and 7-9). WO ‘608 teaches the micelle encapsulates a variety of therapeutic agents including decitabine and pravastatin (pages 12-13).
It would have been obvious to one of ordinary skill in the art to select and use a PEG having an average molecular weight of 1000 as the PEG compound of Wang, and produce the claimed invention. One of ordinary skill in the art would have been motivated do so because WO ‘608 provided the guidance to do so by teaching that aside from PEG 2000, PEG 1000 is also suitable for use as the PEG for the amphiphile of DSPE-PEG. Thus, an ordinary artisan would have looked to other low molecular weight PEGs including PEG 1000, known to be suitable as the PEG for the amphiphile of DSPE-PEG with a reasonable expectation of providing a resultant amphiphilic micelle, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claims 3 and 6, as discussed above, Wang teaches the kidney targeting peptide is Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid)3-lysine) ((KKEEE)3K)
Regarding claim 7, Wang teaches a cysteine was added to the kidney targeting peptide at the N-terminus to allow for a thioester linkage (pages 5585-5587).
Regarding claims 8 and 9, Wang teaches the cysteine containing kidney targeting peptide was conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)(DSPE-PEG(2000)-maleimide (pages 5585-5587).
Regarding claim 10, Wang teaches the PEG has a weight average molecular with of 2000 Daltons (pages 5585-5587).
Regarding claims 12 and 13, Wang and Perumal teaches the therapeutic agent is located within the micelle (Wang: pages 5585-5587; Perumal: [0022]-[0039] and claims 8 and 19).
Regarding claims 14 and 15, Perumal teaches and provide the guidance for selecting and using curcumin (an mTOR inhibitor) as the therapeutic agent that is carried by the micelle ([0010], [0022]-[0039], [0135] and [0213]-[0214], and claims 8, 12 and 19).
Regarding claims 16 and 17, as discussed above, WO ‘608 teaches an amphiphilic mixed micelle having a hydrophobic core and a hydrophilic corona, wherein the micelle contains amphiphilic copolymer such as DSPE-PEG, wherein suitable PEGs include PEG having an average molecular weight of 1000 and 2000 (pages 1-2 and 7-9). WO ‘608 teaches the micelle encapsulates a variety of therapeutic agents including decitabine and pravastatin (pages 12-13). Thus, WO ‘608 provided the guidance for incorporating decitabine or pravastatin as the therapeutic agent in the micelle of Wang by teaching that aside from PEG 2000, PEG 1000 is also suitable for use as the PEG for the amphiphile of DSPE-PEG. Thus, an ordinary artisan would have looked to other low molecular weight PEGs including PEG 1000, known to be suitable as the PEG for the amphiphile of DSPE-PEG with a reasonable expectation of providing a resultant amphiphilic micelle.
Regarding claim 18, Perumal teaches and provide the guidance for selecting and using nucleic acid as the therapeutic agent that is carried by the micelle ([0135], [0163]; claim 9).
Regarding claim 21, Perumal teaches and provide the guidance for using gelatin as a material for the carrier ([0173]-[0176]).
Regarding claim 22, Sosin teaches a nanoparticle composition in the form of micelles, wherein the micelle is an amphiphilic micelle which encapsulate therapeutic agents, wherein the nanoparticle composition is formulated for oral administration containing a carrier that include an enteric coating such as cellulose acetate, gelatin, or chitosan (Abstract; [0008], [0061]-[0110], [0199]-[0200], [0207]-[0214], [0135]). Sosin teaches the use of enteric coating such as cellulose acetate provides a drug delivery system which provides controlled release of the therapeutic agent ([0008]). Thus, Sosin provides the guidance for incorporate an enteric coating such as cellulose acetate as the oral pharmaceutically acceptable carrier that is used for formulating the drug delivery system of Wang in view of Perumal by teaching that enteric coating such as cellulose acetate is a suitable material as carrier for formulating an oral drug delivery system so as provide a controlled release drug delivery system. Thus, an ordinary artisan looking to formulate a controlled release drug delivery system would have looked to incorporating an enteric coating such as cellulose acetate as the oral pharmaceutically acceptable carrier that is used for formulating the drug delivery system of Wang in view of Perumal.
Regarding claim 25, as discussed above, Sosin teaches the crosslinked chitosan is chitosan crosslinked with tripolyphosphate.
Regarding claims 27-31, Wang teaches the micelle contains a kidney-targeting multimodal micelle system of DSPE-PEG(2000)-Cy7:DSPE-PEG(2000)-(KKEEE)3-K:DSPE-PEG(2000)-Methoxy (pages 5585-5587).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (Nano Research, 2018, 11(10): 5584-5595; cited in ISR filed 11/11/2022) in view of Perumal et al( US 2012/0219600 A1; previously cited), Sosin et al (US 2016/0113881 A1), and Wang et al (WO 2019/128608 A1; English translation and citation via EPO; hereafter as “WO ‘608”), as applied to claim 1 above, and further in view of Miroshnichenko et al (Frontiers in Pharmacology, May 2019, 10(488): 1-17).
The drug delivery system of claim 1 is discussed above, said discussion being incorporated herein in its entirety.
Regarding claim 19, Miroshnichenko teaches microRNA (miRNA)-targeted therapeutics in which synthetic antisense oligonucleotides (or anti-miRNA Ons) are used for decreasing the hyperexpression of miRNAs, and said synthetic antisense oligonucleotides are suitable for formulating in micelle (Abstract; pages 4-7).
It would have been obvious to one of ordinary skill in the art to incorporate a synthetic antisense oligonucleotides or anti-miRNA Ons as the therapeutic agent in the micelle of Wang, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Miroshnichenko provided the guidance to do so by teaching that synthetic antisense oligonucleotides (or anti-miRNA Ons) is a suitable therapeutic agent for including in micelle drug delivery system, and Perumal indicated that any nucleic acids are suitable for encapsulation in micelles (Perumal: [0135], [0163]; claim 9). Thus, an ordinary artisan would have looked to nucleic acid such as antisense oligonucleotides or anti-miRNA Ons known to be suitable as the active substance that can be encapsulated in micelles so as to provide a desired drug delivery system, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (Nano Research, 2018, 11(10): 5584-5595; cited in ISR filed 11/11/2022) in view of Perumal et al( US 2012/0219600 A1; previously cited), Sosin et al (US 2016/0113881 A1), and Wang et al (WO 2019/128608 A1; English translation and citation via EPO; hereafter as “WO ‘608”), as applied to claim 1 above, and further in view of Zhang et al (US 2016/0153005 A1).
The drug delivery system of claim 1 is discussed above, said discussion being incorporated herein in its entirety.
Regarding claim 20, Zhang teaches nanoparticles of CRISPR enzyme mRNA encoding PKD1, PKD2 and PKHD1 for use in medicine, therapy, or manufacture of a medicament, wherein the nanoparticles of CRISPR enzyme mRNA is provided in any delivery system including micelles (Abstract; [0035], [0007], [0035], [0396], [0404] and [0678]).
It would have been obvious to one of ordinary skill in the art to incorporate CRISPR enzyme mRNA encoding PKD1, PKD2 and PKHD1 as the therapeutic agent in the micelle of Wang, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Zhang provided the guidance to do by teaching that CRISPR enzyme mRNA encoding PKD1, PKD2 and PKHD1 is used a medicament and such medicament is suitable for delivery from micelles. Thus, an ordinary artisan would have looked to therapeutic agents such as CRISPR enzyme mRNA encoding PKD1, PKD2 and PKHD1 known to be suitable as an active substance that can be encapsulated in micelles so as to provide a desired drug delivery system, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (Nano Research, 2018, 11(10): 5584-5595; cited in ISR filed 11/11/2022) in view of Perumal et al( US 2012/0219600 A1; previously cited), Sosin et al (US 2016/0113881 A1), and Wang et al (WO 2019/128608 A1; English translation and citation via EPO; hereafter as “WO ‘608”), as applied to claim 1 above, and further in view of Chu et al (US 2011/0150999 A1).
The drug delivery system of claim 1 is discussed above, said discussion being incorporated herein in its entirety.
Regarding claim 26, Chu teaches chitosan derivatives including a crosslinked chitosan having an degree acetylation from 60-99%, as a suitable carrier material in a drug delivery system to provide controlled release of a therapeutic agent (Abstract; [0026]-[0029], [0116]-[0117], [0131]).
It would have been obvious to one of ordinary skill in the art to use a crosslinked chitosan having an degree acetylation from 60-99% as the carrier material of Wang in view of Perumal and Sosin, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Chu teaches a crosslinked chitosan having an degree acetylation from 60-99% as a suitable crosslinked chitosan that can be used a carrier material for formulating a controlled release drug delivery system. It is noted that the crosslinked chitosan having an degree acetylation from 60-99% of Chu overlaps the claimed acetylated chitosan having a degree of acetylation from about 70 to 98 mole percent. Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization and usage of an acetylated chitosan having a degree of acetylation of about 70 to 98 mole percent would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II). As such, an ordinary artisan would have looked to incorporating a crosslinked chitosan having an degree acetylation from 60-99% as the carrier material of Wang in view of Perumal and Sosin, so as to provide a desired controlled release drug delivery system, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 02/11/2026 have been fully considered but they are not persuasive.
Below is the Examiner’s response to Applicant’s arguments as they pertain the pending 103 rejections.
Applicant argues:
“[n]o reference teaches a kidney targeting peptide conjugated via PEG having a molecular weight less than or equal to 1800 Daltons. Wang teaches the kidney targeting peptide but uses PEG 2000. WO '608 teaches PEG 1000 but does not teach kidney targeting peptides or peptide conjugation to micelles. A person of ordinary skill in the art would have no reason to modify Wang's system by reducing the PEG molecular weight from 2000 to 1800 or below. WO '608 provides no teaching or suggestion that reducing PEG molecular weight would improve kidney targeting of peptide-conjugated micelles. WO '608 uses PEG 1000 for an entirely different purpose in a different type of micelle system. The Examiner has not provided articulated reasoning explaining why a person of ordinary skill would modify Wang's PEG molecular weight based on WO '608. The mere fact that WO '608 discloses PEG 1000 in a different context does not provide motivation to apply that teaching to Wang's kidney targeting peptide micelles.” (Remarks, page 11).
In response, the Examiner disagrees. Both Wang and WO’608 are commonly drawn to micelles containing amphiphilic copolymer such as DSPE-PEG (Wang: pages 5585-5587; WO’608: pages 1-2 and 7-9). The kidney targeting peptides and peptide conjugation to micelles have already been taught by Wang (see 103 rejection, page 8 of this office action). WO ‘608 was used for providing guidance on using other lower molecular weight PEG including PEG 1000 known to be suitable for forming amphiphilic micelles with DSPE, which are the same amphiphilic micelles desired in Wang (see 103 rejection, pages 8-10 of this office action). Thus, as discussed above in pending 103 rejection, it is maintained it would have been obvious to one of ordinary skill in the art to select and use a PEG having an average molecular weight of 1000 as the PEG compound of Wang, and produce the claimed invention. One of ordinary skill in the art would have been motivated do so because WO ‘608 provided the guidance to do so by teaching that aside from PEG 2000, PEG 1000 is also suitable for use as the PEG for the amphiphile of DSPE-PEG. Thus, an ordinary artisan would have looked to other low molecular weight PEGs including PEG 1000, known to be suitable as the PEG for the amphiphile of DSPE-PEG with a reasonable expectation of providing a resultant amphiphilic micelle, and achieve Applicant’s claimed invention with reasonable expectation of success.
As such, contrary to Applicant’s allegation, an articulated reasoning have been provided the Examiner in the obviousness analysis of the pending 103 rejection for why it would have been obvious to one of ordinary skill in the art to select and use a PEG having an average molecular weight of 1000 as the PEG compound of Wang, as a motivation to combine/modify and a reasonable expectation of success in do so have articulated in the obviousness analysis based on the combined teachings of Wang and WO’608, thereby adequately establishing a prima face case of obviousness.
Applicant argues:
“the specification provides evidence of unexpected results that rebut any prima facie case of obviousness. The specification at pages 48-49 and Figure 11C demonstrates that PEG1000-(KKEEE)3K micelles achieved significantly greater kidney accumulation than PEG5000-(KKEEE)3K micelles. Specifically, PEG1000-(KKEEE)3K achieved renal accumulation of 2.43 x 109 + 2.0 x 108 p/s/cm2/sr. PEG5000-(KKEEE)3K achieved only 1.28 x 109 + 2.3 x 108 p/s/cm2/sr. This difference was statistically significant with p < 0.0001. This represents a nearly two-fold improvement in kidney accumulation by using lower molecular weight PEG. The specification explains the mechanism for this unexpected result. PEG1000- (KKEEE)3K micelles were 10.4 + 1.8 nm in diameter. This size is near the reported renal filtration cutoff size. See specification at page 49. The smaller micelle size facilitated kidney targeting by allowing passage through the glomerular filtration barrier. The prior art did not teach or suggest that reducing PEG molecular weight would result in smaller micelles with improved kidney accumulation. This unexpected result is commensurate in scope with the claimed PEG molecular weight limitation of less than or equal to 1800 Daltons. Evidence of unexpected results is sufficient to rebut a prima facie case of obviousness. The nearly two-fold improvement in kidney accumulation with statistical significance of p < 0.0001 demonstrates that the claimed PEG molecular weight limitation produces unexpected and superior results compared to the prior art.” (Remarks, page 11, last paragraph to page 12).
In response, the Examiner disagrees. Applicant’s alleged arguments and evidence of unexpected results shown on pages 48-49 and Figure 11 C of the specification are considered, but found insufficient to obviate the pending 103 rejection as set forth in this office action, for the reasons discussed below.
First, and contrary to Applicant’s allegation, claim 1 is not commensurate in scope with the PEG1000-(KKEEE)3K micelles and micelles size of 10.4 + 1.8 nm that was used in obtaining the alleged unexpected two-fold improvement in kidney accumulation. Thus, it is noted that [w]hether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100°C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110°C and 130°C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60°C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100°C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.). See MPEP §716.02(d).
Second, Applicant’s comparative data in the specification to PEG5000-(KKEEE)3K micelles are also not persuasive and insufficient to obviate the pending 103 rejection as set forth in this office action because with any alleged evidence of unexpected results, said alleged unexpected results must be compared to the closest prior art. In this instant case, the closest prior art is Wang. Applicant has not provide objective evidence comparing to Wang, showing Applicant’s alleged unexpected results was unexpectedly superior to Wang. Thus, it is noted that [w]hether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." See MPEP §716.02(e).
Third, Applicant’s alleged evidence of unexpected results drawn to “improvement in kidney accumulation by using lower molecular weight PEG” and that “smaller micelle size facilitated kidney targeting by allowing passage through the glomerular filtration barrier” are also not persuasive and insufficient to obviate the pending 103 rejection as set forth in this office action because the micelle of Wang is also a small size with an average diameter of 15.0 ± 0.0 and 12.0 ± 2.3 nm, and said micelle was shown to pass through the glomerular filtration barrier to provide enhanced kidney accumulation (see Wang, pages 5588-5590). Thus, Applicant’s alleged unexpected results with respect to “improvement in kidney accumulation by using lower molecular weight PEG” and that “smaller micelle size facilitated kidney targeting by allowing passage through the glomerular filtration barrier” are not unexpected, but rather expected by the teachings from Wang. Thus, it is noted that "[e]xpected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967).
As a result, for at least the reasons discussed above, claims 1, 3, 6-10, 12-22, and 25-31 remain rejected as being obvious and unpatentable over the combined teachings of the cited prior arts in the pending 103 rejections as set forth in this office action.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 6-10, 12-22, and 25-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5 and 12-20 of copending Application No. 18385174 in view of Wang et al (Nano Research, 2018, 11(10): 5584-5595; cited in ISR filed 11/11/2022).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims in the copending application ‘174 significantly overlap with the subject matter of the instant claims, i.e., drug delivery system for oral administration comprising a plurality of nanoparticles including a pharmaceutical acceptable carrier, and a plurality of micelles attached to a targeting peptide, and a therapeutic agent carried by the micelles, wherein the therapeutic agent is a nucleic acid, microRNA, mRNA, or a drug.
Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the copending Application No. 18385174.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 02/11/2026 have been fully considered but they are not persuasive.
Applicant indicated that a terminal disclaimer will be field upon the indication of allowable subject matter. (Remarks, page 13, last paragraph).
In response, the double patent rejection as set forth in this office action is maintained for the reason of record, and pending filing of a terminal disclaimer.
Conclusion
No claim is allowed.
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.
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613
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