DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Amendments to the Claims and Arguments/Remarks filed 13 February 2026, in response to the Office Correspondence dated 14 November 2025, are acknowledged.
The listing of Claims filed 13 February 2026, have been examined. Claims 1-8 and 10-15 are pending. Claims 1, 8, 10, and 14 are amended and are supported by the originally-filed disclosure. Claim 9 is canceled and no new claims have been added.
Response to Amendment
The objection to Claim 14 regarding the recitation of “cerium oxide (CeO)” is considered overcome by the amendment removing “CeO.” The objection to Claim 15 as dependent on Claim 14 is likewise moot. The indefiniteness rejection of Claim 14 regarding “CeO” is withdrawn based on the amendment to the claim.
The rejection under 35 U.S.C. § 112(b) for indefiniteness is maintained as to Claims 8 and 10. The applicant’s amendment of Claim 8 to replace “the surface where the fistula tract arises” with “the peritoneum” does not cure the indefiniteness. The claim now recites “once the solution of nanoparticles is injected in the fistula tract, a pressure is applied on the peritoneum.” This language remains indefinite because the peritoneum is an internal anatomical serous membrane lining the abdominal cavity that is not readily accessible for direct external pressure application in the context of treating an anoperineal fistula. A fistula tract originating in the anoperineal area does not anatomically contact or arise from the peritoneum. Applying pressure on the peritoneum to treat an anoperineal fistula is anatomically confusing and would require an invasive abdominal approach not supported by the specification. A person of ordinary skill in the art would be unable to determine with reasonable certainty how to perform this step. Because claim 10 depends from claim 8 and the indefiniteness of claim 8 is not cured, claim 10 is indefinite for the same reasons. Accordingly, the metes and bounds remain unclear per Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898 (2014). The rejection of claims 8 and 10 under 35 U.S.C. § 112(b) is maintained.
The applicant’s traversal of the prior rejections under 35 U.S.C. § 103 is noted but is unpersuasive, as outlined in the Response to Arguments. However, the prior rejections of the claims under 35 U.S.C. § 103 have been withdrawn based on the amendment to claim 1 including an additional limitation, and the claims are further rejected with a new supplemented ground of rejection under 35 U.S.C. § 103, based on the amended claims as outlined below.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 14 November 2025, since the art which was previously cited continues to read on the amended/newly cited limitations.
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 Applicant regards as his invention.
Claims 8-10 are 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, regards as the invention.
Regarding claim 8, the phrase "a pressure is applied on the surface where the peritoneum" is indefinite. The claim language does not provide reasonable certainty regarding the location and manner of applying pressure, which is not further elucidated in the specification (see Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 909 (2014)).
The peritoneum is an internal anatomical serous membrane lining the abdominal cavity that is not readily accessible for direct external pressure application in the context of treating an anoperineal fistula. A fistula tract originating in the anoperineal area does not anatomically contact or arise from the peritoneum. Applying pressure on the peritoneum to treat an anoperineal fistula is anatomically confusing and would require an invasive abdominal approach not supported by the specification. A person of ordinary skill in the art would be unable to determine with reasonable certainty how to perform this step. The claim fails to clarify whether pressure is applied externally (e.g., perianal region) or internally (e.g., surgical manipulation), the mechanism by which pressure is transmitted to the peritoneum, and the clinical context (e.g., open surgery versus a minimally invasive procedure).
Dependent claim 10 is included in the rejection of claim 8 because it does not cure the defects noted above. Appropriate correction is required to clarify ambiguous claim language.
New Rejections
The following new rejections are made from the previous Office Correspondence dated 14 November 2025, as the Applicant's amendment necessitated the new grounds of rejection presented below based on the amended/newly cited limitations. These rejections contain revised rejections under 35 U.S.C. § 103 addressing the amendments to claims 1, 8, 10, and 14, including the newly added limitation that "the solution does not contain gelatin" in claim 1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. § 102 and 103 (or as subject to pre-AlA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AlA) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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 1-5, 7, 8, 10, 11, and 13-15 are rejected under 35 U.S.C. § 103 as being unpatentable over Khademosseini and Oklu (WO2017069822A2; publication 27 April 2017, herein after referred to as “Khademosseini”) in view of Marzo et al. (Management of perianal fistulas in Crohn's disease: an up-to-date review. World J Gastroenterol. 2015 Feb 7;21(5):1394-403; herein after referred to as “Marzo”), in further view of Meddahi-Pellé et al. (Organ repair, hemostasis, and in vivo bonding of medical devices by aqueous solutions of nanoparticles. Angew Chem Int Ed Engl. 2014 Jun 16;53(25):6369-73; electronically published 2014 Apr 16, hereinafter referred to as “Meddahi-Pellé”).
Khademosseini teaches a method of treating a fistula and associated hemorrhage at the site of the fistula (claims 28 and 29) in patients that suffer from gastrointestinal medical disorder including inflammatory bowel (claims 12 and 13) and hemorrhage associated with inflammatory bowel disease or Crohn's disease (page 27, lines 8-20). Khademosseini injecting a therapeutically effective amount a shear-thinning composition containing silicate nanoparticles having a diameter from about 5-60 nm into a subject’s fistula tract locally at the site of trauma/hemorrhage (claims 16, 17, 34, 45, 52, and 76), wherein embodiments may include metal iron oxide nanoparticles (page 34, lines 19-20) and additional therapeutic agents including an anti-inflammatory agent (e.g., a TNFα inhibitor; claim 43). Khademosseini teaches aqueous solutions (claims 103 and 104), wherein the nanoparticle concentration is 0.5-30 wt% (approx. 5-300 mg/mL; example formulations at 22.5, 45, 67.5, 15, 30, 45, 15, and 22.5 mg/mL, claim 58, and page 23, line 23 - page 24, line 7) and compositions are injectable and can be administered via a catheter and flow with minimal applied pressure during injection (page 18, lines 21-27).
Since Khademosseini teaches silicate nanoparticles having a diameter from about 5-60 nm (claim 34), selecting nanoparticles of 5, 10, 15, or 20 nm from this range would be a matter of routine experimentation and optimization (see KSR, 550 U.S. at 417 (2007), wherein he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results). However, Khademosseini does not explicitly teach the fistula is specifically an anoperineal lesion of instant claim 1 or wherein the solution does not contain gelatin as the newly added limitation of instant claim 1, nor wherein the anti-inflammatory agent is specifically a TNFα blocking agent of instant claim 13.
Marzo supplies the anoperineal/perianal fistula context and TNFα blocking agent teaching. Marzo teaches perianal fistulae are common in the inflammatory bowel disease Crohn's disease, local injection therapies (e.g., fibrin glue, stem cell suspensions, or sealants) are used to close fistulous tracts (page 6, left column, paragraphs 2-4) and the use of anti-tumor necrosis factor alpha (TNF-α) inhibitors, such as infliximab, adalimumab and certolizumab pegol, to improve the management of perianal fistulas (page 4, right column, paragraphs 2-3) with local injection of anti-TNF-α into the fistula tract (page 6, left column, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to apply Khademosseini's injectable nanoparticle fistula sealing method to perianal/anoperineal fistulas in Crohn's disease because Marzo expressly teaches that perianal fistulae are common in Crohn's disease, and local injection therapies (fibrin glue, sealants) are already used to close such fistulous tracts (page 6, left column, paragraphs 2-4). A person of ordinary skill would recognize that Khademosseini's nanoparticle composition serves the same function (sealing fistulas) as the known injectable sealants, making it an obvious alternative or improvement.
It would have been obvious to co-administer a TNFα blocking agent with Khademosseini's composition because Marzo teaches that local injection of anti-TNF-α into the fistula tract" is an established treatment for perianal fistulas in Crohn's disease (page 6, left column, paragraph 2). The combination of a sealing agent with an anti-inflammatory agent would have been recognized as a synergistic approach to enhance healing and reduce inflammation, wherein combination therapies for synergistic tissue repair were well known in the art (see In re Kerkhoven, 626 F.2d 846 (C.C.P.A. 1980)). However, Marzo does not address nanoparticles or the gelatin-free limitation.
Khademosseini teaches a composition containing both gelatin and silicate nanoparticles, wherein shear-thinning behavior was not observed with gelatin or nanoparticles alone, but that both were required for the desired effect (page 20, lines 13-16). This could be viewed as teaching away from a gelatin-free composition if shear-thinning were a claimed property, however, claim 1 does not require shear-thinning, matrix formation, or promotion of the clotting cascade.
Even accepting that Khademosseini's preferred embodiment includes gelatin, the reference does not teach that gelatin is essential for all embodiments. Khademosseini explicitly contemplates iron oxide nanoparticles as diagnostic agents (page 34, lines 19-20) and teaches that the composition may include various therapeutic agents. The shear-thinning property taught in Khademosseini is a benefit of the gelatin-nanoparticle combination, but a person of ordinary skill would recognize that the composition could still be administered (e.g., via catheter, as taught at page 18, lines 21-27) without shear-thinning behavior, albeit potentially with different flow properties. Eliminating an optional component to simplify a composition does not confer patentability.
A person of ordinary skill in the art would have been motivated to simplify the composition by removing components that are not essential for the intended therapeutic function (fistula sealing). The desire to reduce potential toxicity, lower production costs, and avoid adverse immune responses by eliminating unnecessary excipients is a technology-independent motivation recognized as generally desirable (see Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356, 1368 (Fed. Cir. 2006), recognizing that motivation to simplify or improve a process is within the knowledge of an ordinary artisan).
Where a simpler formulation (gelatin-free) would be expected to work based on known nanoparticle adhesion mechanisms, a person of ordinary skill would have been motivated to pursue it. The rationale to combine may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent (see MPEP 2144). The motivation need not be expressly stated in a reference but may be inferred from the nature of the problem to be solved (see KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, at 420-421 (2007).
Moreover, Meddahi-Pellé teaches that aqueous nanoparticle solutions alone, without gelatin or other adhesives, can achieve effective tissue sealing and hemostasis. Thus, a person of ordinary skill would have known that the adhesive component (gelatin) was not strictly necessary for fistula sealing and could be eliminated. The fact that Khademosseini teaches a different mechanism (shear-thinning) does not preclude the existence of an alternative, simpler mechanism (nanoparticle packing/adhesion) that would have been obvious to try.
Meddahi-Pellé teaches the use of iron oxide nanoparticles for wound closure (Abstract) using aqueous solution of Fe₂O₃ 20-40 nm nanoparticles at a concentration of 42.2 g/L [42.2 mg/mL] (page 2, paragraph 4 and Supplementary Materials, page 2, paragraph 2), wherein the solution is applied by micropipette followed by gentle pressure to the surface where the wound arises for up to one minute after which time the wound had closed and did not reopen (page 2, right column, paragraph 3). The composition does not require gelatin or other adhesive agents and functions via nanoparticle adhesion alone.
Khademosseini and Marzo, as combined above, do not explicitly teach application of pressure following nanoparticle injection, pressure applied for at least 60 seconds, and the specific list of metal oxides in claims 14 and 15. Meddahi-Pellé supplies the teaching of applying pressure up to one minute that after applying an aqueous iron oxide nanoparticle solution to a wound. A fistula tract is a wound with an internal surface, wherein a person of ordinary skill would recognize that applying pressure to the external orifice or surrounding tissue would ensure the nanoparticle solution effectively seals the tract, just as pressure is applied to hold the edges of a linear wound together. The application of pressure following nanoparticle injection is thus an obvious adaptation of Meddahi-Pellé's teaching to the fistula context.
Regarding the applicant's amendment to claim 8 reciting "pressure is applied on the peritoneum", the indefiniteness rejection under 35 U.S.C. § 112(b) as set forth above and further described in light of the amendment is maintained. Even assuming arguendo that the peritoneum is anatomically relevant, Meddahi-Pellé's teaching of applying pressure to the surface where the wound arises would have rendered obvious the application of pressure to adjacent tissue, including peritoneum, for the same purpose.
Wherein Meddahi-Pellé teaches applying pressure for up to one minute (60 seconds) (page 2, right column, paragraph 3), a person of ordinary skill would understand that a more complex and irregular fistula tract (see Marzo, Introduction and Classification sections) may require pressure for at least the maximum time taught for simple surgical wounds, or longer, to ensure a robust seal. Selecting a pressure duration of at least 60 seconds is a predictable routine optimization (see KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007), wherein predictable variations are likely obvious). The claimed time does not represent an inventive departure from the prior art.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to u the specific metal oxides of instant claims 14 and 15 given Khademosseini teaches that embodiments may include iron oxide nanoparticles (page 34, lines 19-20) and broadly teaches silicate nanoparticles and Meddahi-Pellé specifically teaches the use of Fe₂O₃ (iron oxide) nanoparticles for tissue sealing (Abstract). A person of ordinary skill would have been motivated to substitute or additionally use the specific iron oxide nanoparticles taught by Meddahi-Pellé because they are a species within the genus of metal oxides disclosed by Khademosseini, and Meddahi-Pellé demonstrates their efficacy in wound closure. Regarding the other metal oxides recited in claim 14 (cerium oxide, aluminum oxide, zirconium oxide, titanium oxide, titanates, indium oxide, tin oxide, antimony oxide, magnesium oxide, calcium oxide, manganese oxides, molybdenum oxide, silica, zinc oxide, yttrium oxide, bismuth oxychloride, copper oxides), these were known in the art as biocompatible metal oxide nanoparticles for biomedical applications, and selecting a particular metal oxide from a known class would have been a matter of routine experimentation.
Claims 1, 5, 6 and 12 are rejected under 35 U.S.C. § 103 as being unpatentable over Khademosseini and Oklu (WO2017069822A2; publication 27 April 2017, herein after referred to as “Khademosseini”) in view of Marzo et al. (Management of perianal fistulas in Crohn's disease: an up-to-date review. World J Gastroenterol. 2015 Feb 7;21(5):1394-403; herein after referred to as “Marzo”), in further view of Meddahi-Pellé et al. (Organ repair, hemostasis, and in vivo bonding of medical devices by aqueous solutions of nanoparticles. Angew Chem Int Ed Engl. 2014 Jun 16;53(25):6369-73; electronically published 2014 Apr 16, hereinafter referred to as “Meddahi-Pellé”) and Wahajuddin and Arora (Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers. Int J Nanomedicine. 2012;7:3445-71; electronically published 06 Jul 2012, hereinafter referred to as “Wahajuddin”).
Khademosseini in view of Marzo and Meddahi-Pellé teach the limitations of instant claims 1 and 5, as described above, from which instant claims 12 or 6 depend, however does not teach specific limitations of instant claims 6 or 12.
Khademosseini does not explicitly teach wherein the iron oxide nanoparticles are Fe3O4 Ultrasmall Superparamagnetic Iron Oxide nanoparticles, or wherein the nanoparticles are injected in the fistula tract as an aqueous alcohol solution of nanoparticles. Meddahi-Pellé teaches the use of iron oxide nanoparticles for wound closure (Abstract), as an aqueous solution of Fe2O3 20-40 nm nanoparticles at a concentration of 42.2 g/L [42.2 mg/mL] (page 2, paragraph 4; Supplementary Materials, anie0053-6369-sd3.pdf, page 2, paragraph 2). However, Khademosseini, Marzo, and Meddahi-Pellé, as combined above, do not explicitly teach Fe₃O₄ Ultrasmall Superparamagnetic Iron Oxide (USPIO) nanoparticles specifically or aqueous alcohol solution of nanoparticles.
Wahajuddin teaches SPION Fe₃O₄ (magnetite) nanoparticles with a core ranging between 10 nm and 100 nm in diameter, wherein ultrasmall SPIONs are within the scope (Abstract and page 17, left column, paragraph 2), aqueous alcohol preparations (page 6, Table 1), utility as drug delivery vehicles including for targeted/controlled therapy (Abstract and "Utility as drug delivery vehicles" section) and use as diagnostic agents in magnetic resonance imaging (Abstract) with biocompatibility considerations.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to combine the teachings of Khademosseini, Marzo, Meddahi-Pellé and Wahajuddin with a reasonable expectation of success. Meddahi-Pellé teaches the use of Fe₂O₃ nanoparticles for wound closure. Wahajuddin teaches both superparamagnetic iron oxide Fe₂O₃ and ultrasmall Fe₃O₄ nanoparticles for biomedical applications including MRI imaging and localized drug delivery (Abstract; page 17, left column, paragraph 2). A person of ordinary skill would have been motivated to substitute Fe₂O₃ nanoparticles with Fe₃O₄ USPIO nanoparticles because Wahajuddin teaches that Fe₃O₄ USPIO nanoparticles offer enhanced magnetic properties, potential for targeted/controlled therapy and diagnostic imaging, and improved biocompatibility at effective concentrations (sections on SPION targeting approaches, utility as drug delivery vehicles, and absorption, distribution, metabolism, and excretion of SPIONs). Substituting one known iron oxide nanoparticle for another in a wound sealing composition would have been a routine substitution of a known equivalent with a reasonable expectation of success.
One would be motivation to use aqueous alcohol solution because Wahajuddin teaches that magnetic nanoparticles can be prepared in water-ethanol solvent and that such preparations take advantage of increased solubility and reactivity of metal salts and complexes at elevated temperature and pressure without bringing the solvent to its critical point and avoid agglomeration of metal nanoparticles (page 6). A person of ordinary skill would have been motivated to use an aqueous alcohol solution as the carrier for the nanoparticles to achieve these recognized benefits. The choice of solvent between aqueous versus aqueous alcohol is a routine formulation variable that would not have been expected to fundamentally alter the therapeutic efficacy.
One of ordinary skill in the art would have a reasonable expectation of success in combining the teachings of Khademosseini, Marzo, Meddahi-Pellé, and Wahajuddin with a reasonable expectation of success because Meddahi-Pellé discloses a method of treating tissue lesions by injecting an aqueous Fe₂O₃ nanoparticle solution to induce sealing and healing. Wahajuddin confirms that Fe₃O₄ USPIO nanoparticles are known substitutes for Fe₂O₃ with comparable or enhanced properties. The mechanism of action (nanoparticle packing/interaction with tissue) is similar across iron oxide nanoparticle compositions. The claimed methods do not require any unexpected synergy or novel property beyond the predictable efficacy of the substituted nanoparticle.
Response to Arguments
Applicant Arguments/Remarks of the reply, filed 13 February 2026, have been fully considered.
The applicant argues that Khademosseini teaches away from a gelatin-free composition because gelatin and nanoparticles together are required for shear-thinning behavior (page 20, lines 13-16). This argument is unpersuasive. Claim 1 does not require shear-thinning. The applicant amended claim 1 to exclude gelatin, but claim 1 recites no property (e.g., shear-thinning, matrix formation, or clotting cascade promotion) that would be defeated by the absence of gelatin.
The applicant asserts that removing gelatin would defeat Khademosseini’s purpose. However, this argument is not commensurate with the full scope of the reference. Khademosseini teaches multiple embodiments, including diagnostic and therapeutic uses of nanoparticle-based injectable systems for tissue sealing, where gelatin is one embodiment, not a required element of all compositions. The reference broadly emphasizes injectable nanoparticle systems, hemostatic and sealing functionality, and local administration to tissue defects. The fact that one embodiment uses gelatin does not teach away from a gelatin-free embodiment, particularly where Khademosseini explicitly contemplates iron oxide nanoparticles as diagnostic agents (page 34, lines 19-20). The applicant’s own specification admits that nanoparticle solutions without gelatin are known (¶[0003]). Injecting a nanoparticle solution and applying pressure is a method structurally identical to that of Meddahi-Pellé, which uses no gelatin.
One of ordinary skill seeking to treat an anoperineal fistula would have had a finite number of identified, predictable solutions. Khademosseini teaches nanoparticle-based fistula treatment. Marzo teaches that perianal fistulas are common in Crohn’s disease. The elimination of an excipient, gelatin, to simplify a composition, reduce immunogenicity, and utilize known nanoparticle-only adhesive systems does not confer patentability (see KSR Int’l v. Teleflex, 550 U.S. 398, 421 (2007), wherein the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results).
Nevertheless, a new supplemented rejection for claim 1 and the dependent claims 2-8 and 10-15 has been made as outlined above, further strengthen the rejections in the absence of gelatin.
Regarding the applicant’s amendment to claim 8 to require pressure application on the peritoneum. Meddahi-Pellé explicitly teaches applying an aqueous iron oxide nanoparticle solution to a wound, applying gentle pressure to the surface where the wound arises for up to one minute, and the wound closes and does not reopen. Even assuming the peritoneum were anatomically relevant to an anoperineal fistula, Meddahi-Pellé’s teaching of applying pressure to the wound surface renders the step of applying pressure to any adjacent tissue, including the peritoneum if the wound were abdomen, an obvious and predictable variation. A person of ordinary skill would understand that applying pressure to the tissue surrounding a fistula tract (whether perianal skin, perineum, or peritoneum) serves the identical purpose ensuring contact, promoting sealing, and preventing leakage. No inventive skill is required to select a location for pressure application that is anatomically adjacent to the lesion.
The applicant’s argument that Marzo is completely silent regarding the use of nanoparticles is not persuasive. Marzo is not relied upon for teaching nanoparticles, rather it is relied upon for teaching that perianal fistulas are common in IBD and Crohn’s disease, local injection therapies (e.g., fibrin glue, stem cells, sealants) are used to close fistulous tracts, and TNFα inhibitors are injected locally into fistula tracts, providing a motivation to optimize local treatments. Khademosseini provides the nanoparticle-based sealing composition. The combination is proper because Marzo supplies the motivation to apply Khademosseini’s composition to the specific anatomical location (anoperineal) and disease state (Crohn’s disease) and to co-administer a TNFα blocker. The fact that Marzo does not itself disclose nanoparticles is irrelevant, the test is whether the combined teachings of the references would have rendered the claimed invention obvious (see In re Keller, 642 F.2d 413 (CCPA 1981)). Substitution of known injectable materials (nanoparticles) into known treatment paradigms is prima facie obvious under KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007).
The applicant argues Khademosseini teaches iron oxide only diagnostically. This is not persuasive. Khademosseini discloses nanoparticles broadly as functional components in therapeutic compositions. The applicant further argues that Meddahi-Pellé does not compensate for deficiencies is similarly unpersuasive. Meddahi-Pellé is relied upon to teach magnetic nanoplatforms as drug carriers teaches therapeutic delivery and tissue interaction of iron oxide nanoparticles, the use of aqueous solutions of iron oxide (Fe₂O₃) nanoparticles for therapeutic tissue sealing, application of pressure for up to 60 seconds to achieve closure, and that nanoparticle solutions alone (without gelatin) are effective for wound closure.
The combined art clearly supports therapeutic use of nanoparticles, including iron oxides. Khademosseini teaches nanoparticle fistula treatment, Marzo teaches the specific anoperineal/Crohn’s context, and Meddahi-Pellé teaches the specific nanoparticle material (iron oxide) and the post-injection pressure step. One of ordinary skill would have been motivated to combine these teachings because each addresses a different aspect of the same problem, sealing a fistulous tract.
The applicant argues that Wahajuddin does not compensate for deficiencies is rejected. Wahajuddin is properly relied upon to teach ultrasmall superparamagnetic iron oxide (USPIO) Fe₃O₄ nanoparticles and aqueous alcohol solutions for nanoparticle preparation and that such nanoparticles are known for localized delivery and biocompatibility. Substituting Fe₂O₃ (Meddahi-Pellé) with Fe₃O₄ USPIO (Wahajuddin) is a routine substitution of a known equivalent. Using an aqueous alcohol solution rather than pure aqueous solution is a predictable variation in nanoparticle preparation chemistry. No unexpected results are asserted.
In summary, claims 1-8 and 10-15 are remain rejected under 35 U.S.C. § 103 as unpatentable over the cited prior art combinations as set forth herein to supplement the previous rejections.
Conclusion
No claims are allowed.
The 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 (87 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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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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