DETAILED 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 .
Election/Restrictions
To summarize the current election, the applicant elected Group I and the species, where the implant associated complication is foreign body response and the mechanotransduction inhibitor is an inhibitor of RAC2, without traverse.
The requirement was deemed proper and made FINAL.
The amendment to the claims limited instant claim 4 to administering a composition comprising a mechanotransduction inhibitor of IQ Motif containing GTPase activating protein 1 and it is not evident that such an inhibitor is embraced by the species election of an inhibitor of RAC2. Therefore claim 4 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites “a mechanotransduction inhibitor of RAC1 or RAC2” which is rather awkward because it reads as though the inhibitor acts via mechanotransduction to inhibit RAC1 or RAC2. The specification discusses mechanotransduction inhibitors that are also inhibitors of RAC1 or RAC2 which seems to be a slightly different distillation of the role of the mechanotransduction inhibitor, where the inhibiting action stops the transmission of the mechanical stimulus through the tissue. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1, 5, and 9 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.
Claim 1, the independent claim, recites that administering the composition to a human does one or more of “(a) reducing myofibroblast activity by at least 20% relative to an untreated control, (b) reducing mechanoresponsive immune cells activity by at least 20% relative to an untreated control; and (c) reducing FBR capsule formation by at least 20% relative to an untreated control”. The disclosure has no discussion of composition formulations or dosing regimen that correspond to particular degrees of reduction of any outcome in a human individual. The tests performed by the applicant administered a 10 mg/kg daily dose of the RAC2 inhibitor EHT 1864 for 27 days via daily injection in mice, then assessed various outcome indicators at day 28 (see specification paragraph 146). The claims do not recite a time point for assessment, thus they embrace the recited degrees of reduction occurring at any time after an initial administration of a claimed composition, in spite of the applicant only discussing a single assessment time point. In addition, it is not evident how the composition would need to be configured in regard to concentration and dosing in order to achieve the degree of difference that is claimed in humans. The responsiveness of one species to a drug is not the same as another. For example, a comparison of a rat and pig foreign body response and the impact of local drug release of drug to reduce the foreign body response from an implant found the same implants to be less effective at thwarting the foreign body response in the pig than in the smaller rat (see Kastellorizios et al. Journal of Controlled Release 2015 202:101-110, page 103 second column last partial paragraph-page 104 second column first partial paragraph and page 106 first column first-second full paragraphs). While the action of RAC2 in the process of foreign body response is explored in fibrous capsule tissue derived cells and in a mouse model by the applicant, the disclosure does not describe the structural aspects of the method necessary for the claimed methods to function as recited in humans.
Additionally, there is not full alignment between the scope of functions that are instantly claimed and those that are disclosed. For example, the activity of fusogenic macrophages and lymphocytes is recited to be reduced by at least 20% in the specification, but all the “activity” of all the cells embraced by the recitation “mechanoresponsive immune cells activity” (e.g., monocytes) is not discussed (see Fahy et al. Frontiers in Immunology 2019 10:383:1-12; page 10 first column last partial paragraph-second column first partial paragraph).
As a result, the artisan of ordinary skill would not have deemed the applicant to be in possession of the invention as currently claimed at the time of filing.
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.
Claims 1, 5, and 9 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The scope of outcomes embraced by the recitation “myofibroblast activity” is not clear. The specification discusses measuring the presence of myofibroblast activation via staining for alpha smooth muscle actin (see specification paragraphs 26 and 152). There is additional discussion of myofibroblast differentiation resulting in collagen deposition (see paragraph 128). The presence of collagen is also detailed as a part of the foreign body response capsule and the reduction in the formation of the capsule is separately claimed as an outcome (see paragraph 26). Thus it is not clear which outcomes need to be assessed in order to make the comparison recited in the claims.
Similarly the scope of activities embraced by the recitation “mechanoresponsive immune cells activity” also is not clear such that the outcomes that need assessment in order to make the comparison recited in the claims is apparent.
Claims that are rejected but are not explicitly elaborated upon are also indefinite because they depend from an indefinite claim and do not add clarity; therefore they are also indefinite.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 5, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Kyriades et al. (previously cited) in view of Bornstein et al. (US PGPub No. 2003/0129214) as evidenced by Fahy et al.
Kyriades et al. teach implants with a Rho GTPase activity antagonist as part of its surface to inhibit foreign body response (see abstract and page 3 lines 21-25 and page 4 lines 1-5 and example 6; instant claim 1). The implants of particular concern that they discuss include glucose sensors and breast augmentation prosthesis due to the malfunctions and failures the foreign body response is known to induce (see page 1 lines 18-29). NSC23766 is the preferred Rho GTPase activity antagonist (see abstract and page 3 lines 30-32). An example implants a composite polymer subcutaneous implant of polymer mixed with NSC23766 or the drug free implant in several mice (see example 6); instant claims 1, 5, and 9). The occurrence of foreign body giant cells, whose formation indicates the presence of a foreign body response, was assessed after two weeks and compared between the two types of implants (see example 6 and page 2 line 9-page 3 line 5). The approximately 11 mg implant containing NSC23766 produced 5 mg/mg of scaffold per day and induced significantly fewer foreign body giant cells than the drug free comparison device and, more specifically, inhibited the formation of foreign body giant cells by more than 50% (see example 6 and figure 4). Foreign body giant cells form due to the fusion of macrophages which are mechanoresponsive immune cells; thus the greater then 20% reduction in foreign body giant cell formation is a greater than 20% reduction in the activity of a type of mechanoresponsive immune cell (see Fahy et al. page 5 first column last partial paragraph; instant claim 1). Kyriades et al. teach that fewer foreign body giant cells form from monocytes as the concentration of NSC23766 increases (see page 4 lines15-18). Monocytes are the mechanoresponsive precursor cells of macrophages which yield the foreign body giant cells (see page 1 line 30-33 and Fahy et al. page 10 first column last partial paragraph-second column first partial paragraph). Administration to humans is not explicitly discussed.
Bornstein et al. also teach inhibiting the foreign body response to an implant by including an antagonist to the process in the implant (see paragraphs 4-6). The implants of particular concern that they discuss include glucose sensors and breast augmentation prosthesis due to the malfunctions and failures the foreign body response is known to induce (see paragraph 40. They go on to teach these implant devices employed in humans (see paragraph 9).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implant a device of Kyriades et al. that has a polymer comprising and releasing NSC23766 on its surface into a human in need of treatment with the device in order to inhibit the foreign body reaction elicited by the presence of the device. This choice of subject/patient would have been obvious in light of Bornstein et al. who teach humans as the target individual in need of protection from foreign body response that can be facilitated by the incorporation of an antagonist to the process in the device itself. Since the degree of impact of NSC23766 on foreign body giant cell formation inhibition increases with concentration, this parameter is a result effective parameter and thus it is obvious to optimize as a matter of routine experimentation. Further, MPEP 2145II discusses that mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). In addition, the fact that an inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). The method rendered obvious by the prior art conducts the instantly claimed active steps with the instantly claimed product on the instantly claimed patient population, thus the corresponding impact on mechanoresponsive immune cells would occur. Therefore claims 1, 5, and 9 are obvious over Kyriades et al. in view of Bornstein et al. as evidenced by Fahy et al.
Response to Arguments
Applicant's arguments filed March 27, 2026 have been fully considered. In light of the amendment, the objection to the specification and rejection under 35 USC 102 are hereby withdrawn. The applicant’s argument directed toward the amended claims meeting the requirements of 35 USC 112 and prior art based statutes are not persuasive.
The applicant argues that the claim language has been aligned to the data provided in the examples. However the examples provide mouse data and detail effectiveness of a claimed RAC2 inhibitor against various aspects of the foreign body response in mice, but the claims are drawn to treating humans. There is no clear parallel between the degree of impact of the claimed inhibitor compounds on foreign body response in mice and the degree of impact of the claimed inhibitor compounds on foreign body response in humans. The applicant notes that a human like foreign body response occurs in mice when implanted with a mechanically stimulating implant. There is no corresponding evidence that this similarity equates to the degree of impact of administering a RAC2 inhibitor on foreign body response in mice is the same as when administered to humans. In fact, different animal species are known to have their foreign body response impacted to different degrees by the same inhibitor, as noted in the new rejection under 35 USC 112(a). Thus the amendment does not align the claim scope to the data that was provided in the disclosure.
The applicant also notes a teaching in Kyriades et al. that notes that a difference in foreign body giant cell formation due to NSC23766 administration did not correlate with foreign body response capsule formation. However, the instant claim recites reducing mechanoresponsive immune cell activity as an indicator of treating foreign body response. Foreign body giant cell formation reduction is a reduction in mechanoresponsive immune cell activity because these cells originate from the fusion of mechanoresponsive immune cells. Kyriakides et al. detail that the activity of the foreign body giant cells is not directly involved in the capsule formation of the foreign body response, but instead is an indicator that the macrophages from which they originate are a pivotal cell type active in the foreign body response (see American Journal of Pathology 2004 165:2157–2166; page 2165 first column second full paragraph). Further, they detail that the foreign body giant cells degrade the surface of implanted biomaterials which is a response to the presence of a foreign body (a foreign body response) that could compromise the implant (see Kyriakides et al. page 2165 first column last partial paragraph-second column first partial paragraph). Even if the number macrophages present due to the NSC23766 treatment was no different than when the compounds was absent, as the applicant notes, the level of activity of the macrophages was reduced as indicated by the reduction of their fusion into foreign body giant cells. Thus the administration of the NSC23766 via an implant to thwart the deleterious impact of the body’s reaction to the implant’s presence is still a useful method to practice on a patient receiving an implant. Kyriades et al. in view of Bornstein et al. administer the same compound that is claimed by the applicant to the same claimed patient population via the same vehicle as that is instantly claimed. According to MPEP 2112.01, “[a] chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” This treatment results from In re Spada, which states that, “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). The applicant does not teach a particular dosing regimen for humans that is distinct from the dosing detailed by Kyriades et al. in a non-obvious manner. Therefore the instantly claimed method is obvious in light of the prior art teaching its steps.
The applicant appears to have explored mechanisms of action of a RAC2 inhibitor in the form of EHT 1684 against foreign body response due to implants that are mechanically stimulated as well as developed a mouse model whose foreign body capsule formation more closely resembles that of humans. While noteworthy, the claims are not limited to administering this compound. Prior art administers another RAC2 inhibitor to the address the body’s reaction to an implant as a foreign body, but does not describe its impact in the same manner. According to MPEP 2144 IV, “[t]he reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).” Thus the prior art is not required to identify the same mechanism of action or rationale in order to render the claimed method obvious and the applicant’s identification of a different mechanism or rationale does not alter the obviousness of the method
The applicant further discusses the impact of IQ Motif containing GTPase activating protein 1 on mechanical signaling. However inhibitors of this protein were not elected, therefore, this argument is not relevant to the claimed species under examination.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARALYNNE E HELM whose telephone number is (571)270-3506. The examiner can normally be reached Mon-Fri 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Wax can be reached at (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CARALYNNE E HELM/ Examiner, Art Unit 1615
/MELISSA S MERCIER/ Primary Examiner, Art Unit 1615
Prosecution Insights