DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed September 01, 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Objections
Claim 7 remains objected to because of the following informality:
Claim 7 is not grammatically correct and should be amended. For example, the claim could read “The composition of claim 6, wherein the composition is administered
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 12 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 12, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 12 recites the broad recitation “Poly(methacrylic acid-co-methyl methacrylate) 1:2”, and the claim also recites (CAS No. 25086-15-1) which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. To overcome this rejection, the parathesis can be removed from the claim.
Claim Rejections - 35 USC § 103 (New, Necessitated by Amendment)
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.
Claims 1 and 6-9 are rejected under 35 U.S.C. 103 as being as being obvious over Wu et al. (J. Mater. Chem. B, 2014, 2, 7410) in view of Lee (WO 2013/051778 A1).
Regarding claim 1, Wu discloses modifying laponite nano disks with folic acid for targeted anticancer drug delivery applications (abstract). Laponite nano disks were modified with 3-aminopropyldimethylethoxysilane (APMES) to render them with abundant surface amines, followed by conjugation with folic acid. The conjugated complex is then bound to a drug (abstract; Scheme 1). The laponite is a magnesium phyllosilicate (pg. 7411, left column, Materials) to which a 3-aminopropyl group (3-aminopropyldimethylethoxysilane) is introduced (abstract).
Wu does not disclose that the drug is an antibody therapeutic agent.
Lee discloses a conjugate used for the treatment of cancer (abstract) with monoclonal antibodies and folic acid as the carrier (abstract; English translation pg. 7, third paragraph). Lee teaches that the antibody is stable during circulation and is rapidly partitioned to produce an activated cytotoxic agent for targeted chemotherapy (pg. 7, third paragraph).
Since Wu generally teaches the delivery of a therapeutic agent for the treatment of cancer with folic acid, it would have been prima facie obvious to one of ordinary skill in the art to include monoclonal antibodies, within the teachings of Wu, because Lee teaches a conjugate used for the treatment of cancer with folic acid and an antibody. The ordinarily skilled artisan would have been motivated to use monoclonal antibodies because Lee teaches that the antibody is stable during circulation and is rapidly partitioned to produce an activated cytotoxic agent for targeted chemotherapy (pg. 7, third paragraph).
Claim 6 is rendered prima facie obvious because Wu discloses the complex is combined with a pharmaceutically acceptable carrier (pg. 7412, left column, bottom paragraph).
Claim 7 is rendered prima facie obvious because Wu discloses the claimed composition and the composition being administered by one of the claimed methods is interpreted as an intended use of the composition.
Claims 8 and 9 are rendered prima facie obvious because Wu discloses the complex is combined with a pharmaceutically acceptable carrier (pg. 7412, left column, bottom paragraph). While “for the prevention or treatment of inflammatory diseases or cancer” is interpreted as an intended use, the composition is capable of being used for the treatment of inflammatory diseases or cancer because Wu discloses the complexes are for anticancer drug delivery applications (abstract).
Claim 5 is rejected under 35 U.S.C. 103 as being as being obvious over Wu et al. (J. Mater. Chem. B, 2014, 2, 7410) in view of Lee (WO 2013/051778 A1) and further in view of Brown et al. (Annals of Oncology, 2008, 19:1340–1346).
The 35 U.S.C. 103 rejection over Wu in view of Lee was previously discussed.
The combined teachings of the prior art do not disclose the antibody therapeutic agent is an infliximab.
Brown teaches that an increasing number of clinical and translational studies have provided evidence for the role of the pro-inflammatory cytokine tumor necrosis factor-α (TNF- α) in the promotion and progression of cancer (pg. 1340, left column) and that infliximab is a monoclonal antibody that acts as an anti-TNF- α antagonist (pg. 1340, right column). Brown teaches that infliximab reduced the serum concentrations of TNF- α in advanced cancer patients and in some patients treated with infliximab the cancer stabilized (pg. 1345, left column).
Since the combined teachings of the prior art generally teach the delivery of a monoclonal antibody for the treatment of cancer, it would have been prima facie obvious to one of ordinary skill in the art to include infliximab, within the combined teachings of the prior art because Brown teaches that infliximab is a monoclonal antibody that acts as an anti-TNF- α antagonist (pg. 1340, right column) and TNF- α may play a role in the promotion and progression of cancer (pg. 1340, left column). The ordinarily skilled artisan would have been motivated to use infliximab because Brown teaches that infliximab reduced the serum concentrations of TNF- α in advanced cancer patients and in some patients treated with infliximab the cancer was stabilized (pg. 1345, left column).
Claims 10-13 are rejected under 35 U.S.C. 103 as being as being obvious over Wu et al. (J. Mater. Chem. B, 2014, 2, 7410) in view of Lee (WO 2013/051778 A1) and further in view of Traverso et al. (US 2021/0046011 A1).
The 35 U.S.C. 103 rejection over Wu in view of Lee was previously discussed.
Regarding claims 10-12, Wu does not disclose that a pH-sensitive polymer is coated on the FA-AC based nanocomposite as recited in claim 10, wherein the pH-sensitive polymer is a poly(methacrylic acid-co-methyl acrylate) copolymer as recited in claim 11, wherein the pH-sensitive polymer is poly(methacrylic acid-co-methyl methacrylate) 1:2 as recited in claim 12.
Traverso teaches an article for the delivery of a therapeutic agent where the article has an associated degradable coating, such as Eudragit S100 (a poly(methacrylic acid-co-methyl methacrylate) 1:2 copolymer) [0078]. Traverso teaches that the degradable coating enables tuning of a release location along the intestinal tract of the subject where the therapeutic agent is released [0052].
Since Wu generally teaches the delivery of a therapeutic agent, it would have been prima facie obvious to one of ordinary skill in the art to include Eudragit S100, within the teachings of Wu, because Traverso teaches Eudragit S100 as a degradable coating on an article for the delivery of a therapeutic agent. An ordinarily skilled artisan would have been motivated to use a degradable coating, such as Eudragit S100, because Traverso teaches that the degradable coating enables tuning of a release location along the intestinal tract of the subject where the therapeutic agent is released [0052].
Claim 13 is rendered prima facie obvious because the complex of Wu is combined with a pharmaceutically acceptable carrier (pg. 7412, left column, bottom paragraph). “For oral administration” is interpreted as an intended use of the composition, nevertheless, the combined teachings of the prior art with Eudragit S100 as a degradable coating are suitable for oral administration as Traverso teaches that the articles with a degradable coating are administered to a subject orally [0083]-[0084].
Response to Arguments
Applicant's arguments filed 09/01/2026 have been fully considered but they are not persuasive.
Applicant argues (at pg. 11 - pg. 12, top) that the folic acid-conjugated aminoclay (FA-AC) of the claimed subject matter and the drug delivery system (LM-FA) with folic acid attached to the surface of the laponite of Wu are clearly distinguishable in terms of chemical structure, synthesis pathway, and surface charge characteristics (e.g., applicant argues that the laponite of Wu is formed by conjugating APMES only to a portion of the surface whereas in the instant invention the aminopropyl groups of the aminoclay are internalized throughout the entire layered skeleton).
The Examiner disagrees because Wu meets all of the structural requirements of the nanocomposite as recited in claim 1 expect for the antibody therapeutic agent (which is taught by Lee). In the disclosure of Wu, a magnesium phyllosilicate is modified to include a 3-aminopropyl group and is conjugated with folic acid, thereby binding the laponite and folic acid via the aminopropyl group of the modified laponite (Scheme 1). This is the same nanocomposite structure as recited in the instant claims. The “distinguishing features” argued by the applicant (i.e., the laponite of Wu is formed by conjugating APMES only to a portion of the surface whereas in the instant invention the aminopropyl groups of the aminoclay are internalized throughout the entire layered skeleton) are not claimed features and, therefore, do not distinguish the claims over the prior art.
Applicant further argues (at pg. 12 bottom – pg. 13, top) that the claimed subject matter is different because the nanocomposites are made through a different method of production than taught by Wu.
The Examiner disagrees because the nanocomposite is claimed, not the method of production, and Wu meets all of the structural requirements of the nanocomposite as claimed expect for the antibody therapeutic agent (which is taught by Lee), as discussed above.
Applicant further argues that neither Lee nor Traverso disclose at all the folic acid-conjugated aminoclay (FA-AC)-based nanocomposite of the claimed subject matter or drug delivery using the same.
The Examiner disagrees because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. Wu discloses the claimed nanocomposite expect where Lee teaches an antibody therapeutic agent and Traverso teaches a poly(methacrylic acid-co-methyl methacrylate) 1:2 copolymer.
Claims 1 and 5-13 are rejected under 35 U.S.C. 103 as being as being obvious over Wu et al. (J. Mater. Chem. B, 2014, 2, 7410) in view of Kim et al. (J Nanobiotechnol, 2020, 18:133).
Regarding claim 1, Wu discloses modifying laponite nano disks with folic acid for targeted drug delivery applications. Laponite nano disks were modified with 3-aminopropyldimethylethoxysilane (APMES) to render them with abundant surface amines, followed by conjugation with folic acid. The conjugated complex is then bound to a drug (abstract; Scheme 1). The laponite is a magnesium phyllosilicate (pg. 7411, left column, Materials) to which a 3-aminopropyl group (3-aminopropyldimethylethoxysilane) is introduced (abstract).
Wu does not disclose that the drug is an antibody therapeutic agent.
Kim teaches the successful formation of antibody drug delivery nanocomposites with aminoclay (pg. 2, right column - pg. 3, left column, top). Kim teaches that this nanocomposite carrier loaded with the antibody, infliximab, provides a colon-specific anti-inflammatory effect without adversely affecting systemic homeostasis (abstract; conclusion; pg. 2, left column).
Since Wu generally teaches an aminoclay for targeted drug delivery, it would have been prima facie obvious to one of ordinary skill in the art to include an antibody, such as infliximab, within the teachings of Wu, because Kim teaches the formation of a drug delivery nanocomposite with animoclay and infliximab. An ordinarily skilled artisan would have been motivated to use the antibody, infliximab, because Kim teaches that aminoclay loaded with the infliximab provides a colon-specific anti-inflammatory effect without adversely affecting systemic homeostasis (abstract; conclusion; pg. 2, left column).
Regarding claim 5, while Wu does not disclose an infliximab, it would have been prima facie obvious to include the antibody, infliximab, as taught by Kim, within the teachings of Wu, as previously discussed.
Claim 6 is rendered prima facie obvious because Wu discloses the complex is combined with a pharmaceutically acceptable carrier (pg. 7412, left column, bottom paragraph).
Claim 7 is rendered prima facie obvious because Wu discloses the claimed composition and the composition being administered by one of the claimed methods is interpreted as an intended use of the composition.
Claims 8 and 9 are rendered prima facie obvious because Wu discloses the complex is combined with a pharmaceutically acceptable carrier (pg. 7412, left column, bottom paragraph). While “for the prevention or treatment of inflammatory diseases or cancer” is interpreted as an intended use, the composition is capable of being used for the treatment of inflammatory diseases or cancer because Wu discloses the complexes are for anticancer drug delivery applications (abstract).
Regarding claims 10-12 Wu does not disclose that a pH-sensitive polymer is coated on the FA-AC based nanocomposite as recited in claim 10, wherein the pH-sensitive polymer is a poly(methacrylic acid-co-methyl acrylate) copolymer as recited in claim 11, wherein the pH-sensitive polymer is Poly(methacrylic acid-co-methyl methacrylate) 1:2 as recited in claim 12.
Kim teaches Eudragit S100 (a Poly(methacrylic acid-co-methyl methacrylate 1:2 copolymer) is a pH-sensitive coating polymer which efficiently degrades and delivers drugs only at colon-specific pH both in vivo and in vitro, thus minimizing drug side effects (pg. 2, left column, bottom – right column).
Since Wu generally teaches the delivery of a therapeutic agent, it would have been prima facie obvious to one of ordinary skill in the art to include Eudragit S100, within the teachings of Wu, because Kim teaches Eudragit S100 as a coating polymer for the delivery of a therapeutic agent. An ordinarily skilled artisan would have been motivated to use Eudragit S100 because Kim teaches Eudragit S100 is a pH-sensitive coating polymer which efficiently degrades and delivers drugs only at colon-specific pH both in vivo and in vitro, thus minimizing drug side effects (pg. 2, left column, bottom – right column).
Claim 13 is rendered prima facie obvious because the complex of Wu is combined with a pharmaceutically acceptable carrier (pg. 7412, left column, bottom paragraph). “For oral administration” is interpreted as an intended use of the composition, nevertheless, the combined teachings of Wu and Kim with Eudragit S100 as a degradable coating are suitable for oral administration as Kim teaches oral delivery is a suitable delivery method for complexes with Eudragit S100 and aminoclays (abstract; pg. 2, left column bottom- pg. 3, right column).
Response to Arguments
Applicant's arguments filed 09/01/2026 have been fully considered but they are not persuasive.
Applicant’s arguments with respect to Wu were discussed above.
Applicant argues at pg. 12, that unlike the folate-conjugated aminoclay (FA-AC) of the claimed subject matter, Kim differs in that a liposome is used as a carrier and the negatively charged surface of the liposome is coated with the positively charged aminoclay.
The Examiner disagrees because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. Wu discloses the claimed nanocomposite expect where Kim teaches the antibody therapeutic agent, infliximab, and a poly(methacrylic acid-co-methyl methacrylate) 1:2 copolymer, which would have been obvious to include within the teachings of Wu for the reasons discussed above.
Analysis of Alleged Unexpected Results
Applicant argues at pg. 13-14 that when folic acid is combined with aminoclay
to form folic acid-conjugated aminoclay (FA-AC) and subsequently combined with an antibody
therapeutic agent (e.g., infliximab) there are improvements in therapeutic effect through targeted selective delivery of the antibody therapeutic agent which cannot be confirmed by the prior art references (i.e., the results are unexpected over the prior art).
The Examiner has fully reviewed and considered the examples in the specification. The results demonstrate that administration of EFA-AC-IFX (Eudragit S100 coated nanocomposites of infliximab and FA-AC) to colitis-induced mice attenuated the progression of disease and was effective in reducing colitis-induced weight loss, tissue damage, and tumor necrosis factor-α (TNF- α) levels compared to control groups (specification, pg. 16-18).
However, these results are not unexpected over the prior art. Kim et al. (J Nanobiotechnol, 2020, 18:133) teaches the benefits of incorporating infliximab with an aminoclay, specifically, 3-aminopropyl functionalized magnesium phyllosilicate. Kim teaches that when infliximab was incorporated with the aminoclay, the nanocomposite carriers targeted to inflamed colitis which minimized systemic exposure, had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score compared to the DSS-treated group, and that aminoclay- infliximab showed significantly higher improvement of the disease activity index, compared to control groups (abstract; pg. 2-6).
Finally, assuming purely arguendo that unexpected results have been established, (the Examiner does not believe at this time that they have), the claims would still not be “commensurate in scope” with the showing. See MPEP § 716.02(d). The Applicant has allegedly demonstrated “improved” benefits of incorporating infliximab (IFX) with an aminoclay nanocomposite, but even if this is so then it would only have been shown with IFX. It is unclear that a comparative composition containing IFX would be reasonably representative of compositions containing other “antibody therapeutic agents” (i.e., other than IFX) falling within the broader scope currently claimed.
Conclusion
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 Ashlee E Wertz whose telephone number is (571)270-7663. The examiner can normally be reached Monday - Friday, 8 AM - 5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ASHLEE E WERTZ/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
