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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/08/2026 has been entered.
Response to Amendment
The amendment filed 04/08/2026, amending claim(s) 84, 96, 101, and 107 is acknowledged.
Claims 84-92, 95-97, 99-101, 104, and 107-112 are pending and under examination.
Withdrawn Rejections
In light of the amendments to the claims, the rejection of claims 84-92, 97, 99-101, 104, 107, and 108 under 35 U.S.C. 103 as being unpatentable over Chatterjee is withdrawn. Applicant added the new limitation of “measuring vascular pathology of the animal before and/or after administering the therapeutic agent”, which is not taught by Chatterjee.
Priority
In light of the Applicant’s comments, the Examiner notes that claims 84-88, 96, 97, 99, 100, 104, and 107-112 are entitled to the priority date of provisional application 63/013,869, filed 4/22/2020.
Claims 89-95 and 101 of the instant case are entitled to the priority date of PCT/US2020/056962, filed 04/21/2021.
Claim Interpretation
Claim 84 recites “a method of screening a therapeutic agent for treatment of a vascular disease”. The examiner notes that the recitation of “for treatment of a vascular disease” in the preamble is interpreted as an intended use of the claimed invention and not a limitation of the claimed invention. “For treatment of a vascular disease” does not limit the structure of the claimed invention; therefore, it does not provide significance to the claim construction.
A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP § 2111.02.II.
In kind, claim 112 is not interpreted to further limit the claimed invention, as the recitation of “wherein the vascular disease is atherosclerosis” does not further limit the structure of the claimed invention.
See further discussion in “Response to Arguments” below.
Claim Objections
Applicant is advised that should claim 84 be found allowable, claim 112 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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.
Claim(s) 84-92, 96, 97, 99-101, 104, and 107-112 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chatterjee (WO2019236722A1, published 12/12/2019; same disclosure as US 20210244638 A1, published 8/12/2021, priority date of 06/05/2018 to provisional application), with support from D12108C Research Diet Inc Information Sheet (accessed 07/23/2025) and further in view of Cao (Cao, M., et al. "AAV2/8-humanFOXP3 gene therapy shows robust anti-atherosclerosis efficacy in LDLR-KO mice on high cholesterol diet." Journal of translational medicine 13.1 (2015): 235.; cited in IDS filed 10/22/2022 10 pgs.).
The Examiner notes that because the disclosure of US 20210244638 is the same as WO2019236722A1, US 20210244638 was used to refer to where the instantly recited limitations are disclosed for ease (e.g., [0145] refers to [0145] of US 20210244638, which is the same disclosure as pg. 55, line 25-pg. 66, line 2 of WO2019236722A1). WO2019236722A1 is included in the application file as well.
Regarding claims 84-88, Chatterjee teaches:
A method of screening a therapeutic agent comprising:
maintaining a low density lipoprotein receptor knockout (LDLR-KO) or Apo E knockout animal on a high cholesterol diet (e.g., western diet- 1.25% cholesterol); and
administering a therapeutic agent to the animal no earlier than 77 days (e.g., e.g., 84 days to 140 days) after beginning the high cholesterol diet [0145- ApoE -/- mice fed western diet (D12108C Research Diet Inc.) from age of 12 to 20 weeks, followed by western diet + biodegradable polymer (BPD)] [0244- ApoE -/- mice fed high fat and high cholesterol diet for 10 weeks prior to use in experiments (TD96121 Teklad Custom Diet)].
Chatterjee does not teach measuring vascular pathology of the animal before and/or after administering the therapeutic agent.
An Artisan, interested in evaluating the effects of therapeutic agents on animals on high cholesterol diets, would be aware of Cao for delivering AAV2/8/hFOXP3 to an LDLR-KO/HCD animal model to study the effects of the gene therapy.
Cao teaches investigating the therapeutic effect of FOXP3 on a vascular disease injecting LDLR-KO mice with two AAV/hFOXP3 (claims 110-112) virus boosters, followed by injections at an interval of 5-6 days. The mice were also fed a high cholesterol diet of 4% cholesterol and 10% cocoa butter starting on the day of the first injection and maintained for the entire study period (Abstract; pg. 2, “Animal treatments”). Additionally, Cao carried out ultrasound imaging to measure the flow velocity and orientation of the abdominal aorta (pg. 2, “Ultrasound imaging”) (claim 96). Ultrasound imaging was done after administering the therapeutic to monitor vascular disease treatment (e.g., Fig. 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to combine the method of Cao with the method taught by Chatterjee by adding the ultrasound imaging step (e.g., measuring vascular pathology) taught by Cao to the method of screening taught by Chatterjee with a reasonable expectation for success. An artisan would have a reasonable expectation of success because measuring the blood flow velocity via ultrasound would not impact the prior method steps of maintaining a knockout animal model and administering a therapeutic agent as taught by Chatterjee. Additionally, both Chatterjee and Cao utilize knockout animal models to study atherosclerosis. One would be motivated to modify the method of Chatterjee to include assessing the blood flow velocity, cross-sectional area of the aorta lumen, and/or the aortic wall thickness of the animal by ultrasound imaging because as taught by Cao, these assessments can be used to measure atherogenesis and the potential clinical use of a therapeutic agent to treat atherogenesis (Abstract).
Chatterjee teaches the diet comprising about 17% cocoa butter (see D12108C document – 155g of cocoa butter/897.35g total).
The instant specification fails to disclose an element of criticality for the amount of cholesterol and cocoa butter in the high cholesterol diet (e.g., there is no disclosure of the importance/difference between 1.25% cholesterol vs. 4% cholesterol) in a method of screening a therapeutic compound.
In addition, there is no clear evidence that the composition of the diet taught by Chatterjee would function different from the diet of the claimed invention, nor that the difference in percentage of cholesterol and cocoa butter comprising the diet is critical (i.e., produces unexpected results).
Further, regarding to the amount of cholesterol and cocoa butter in the high cholesterol diet, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. 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). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Additionally, would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to combine the method of Cao with the method taught by Chatterjee by using a high cholesterol diet of 4% cholesterol and 10% cocoa butter in place of the Western diet taught by Chatterjee with a reasonable expectation of success. An artisan would have a reasonable expectation of success because both Cao and Chatterjee teach atherosclerosis animal models consuming a high cholesterol diet. One would be motivated to use the high cholesterol diet of 4% cholesterol and 10% cocoa butter taught by Cao because as taught by Cao, this HCD successfully resulted in high blood cholesterol levels compared to controls, allowing the researchers to study the efficacy of the therapeutic agent against HCD-associated atherosclerosis (pg. 3, col 1, “AAV vectors and animal treatments”; pg. 4, col 1, para 1; Fig. 2).
Regarding claims 89-92, Chatterjee teaches the diet further comprising sucrose (see D12108C Research Diet Inc.). Additionally, Chatterjee teaches added sugar comprising about 20% (e.g., about 22%) of the energy in the high cholesterol diet (sucrose + lodex 10 (maltodextrin) = 195.41g/897.35g total= 21.7%) (% of energy of diet is interpreted to read on % composition of the diet).
Regarding claim 97, Chatterjee teaches the therapeutic agent being administered no earlier than 12 to 20 weeks (e.g., 84 days to 140 days) after beginning the high cholesterol diet [0145].
Regarding claims 99 and 100, Chatterjee teaches administering the therapeutic agent to the subject once or if multiple doses, separating the doses by days, weeks, or months [0122].
Regarding claims 101 and 104, Chatterjee teaches administering the therapeutic agent parenterally, topically, or by other methods of injection, and through different (e.g., more than one) routes [0016, 0106 (e.g., transdermal patch reads on suspension applied to location of interest), 0110] (Chatterjee claims 8 and 9).
Regarding claims 107 and 108, Chatterjee discloses the therapeutic agent being a cytokine or anti-inflammatory (Chatterjee claim 7).
Regarding claim 109, Chatterjee does not teach the anti-inflammatory molecule being a wildtype or variant FOXP3 polypeptide and/or IL10, and/or a nucleic acid encoding a wildtype or variant FOXP3 polypeptide and/or IL10.
As mentioned above, Cao administers an AAV vector comprising FOXP3 to the LDLR-KO animals (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the vector comprising a FOXP3 polypeptide (e.g., AAV FOXP3 gene delivery) taught by Cao for the therapeutic agent taught by Chatterjee with a reasonable expectation for success. An artisan would have a reasonable expectation of success because the simple substitution of one known element for another (e.g., substituting one therapeutic agent for another) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06. Additionally, both Chatterjee and Cao utilize knockout animal models to study the effect of a therapeutic agent on atherosclerosis.
One would be motivated to replace the therapeutic agent in the method taught by Chatterjee because as taught by Cao, FOXP3 is an anti-inflammatory gene and could potentially be used as a therapeutic agent to limit atherosclerosis (Abstract).
As discussed above, claim 112 further limiting the vascular disease to atherosclerosis does not modify the structure of the claimed method. Thus, claim 112 is rejected by the teachings of Chatterjee (see claim 84 rejection above). In addition, Cao teaches investigating the therapeutic effect of FOXP3 on atherosclerosis (Abstract).
Claim(s) 95 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chatterjee and Cao as applied to claims 84-92, 96, 97, 99-101, 104, and 107-112 above, and further in view of Johansson (Johansson, Maria E., et al. "High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice." Journal of Hypertension 27.1 (2009): 41-47.)
Regarding claim 95, Chatterjee does not teach the high cholesterol diet further comprising added salt, wherein the added salt comprises a sodium-rich chow of about 4% or 8% NaCI, tap water containing about 1% NaCI ad libitum, or both.
An Artisan, interested in studying the effect of high-salt diets, would be aware of Johansson for studying the outcomes of ApoE -/- mice on a high-salt diet.
Johansson investigates the effect of excess dietary salt on atherosclerosis (Objective). Johansson teaches providing ApoE -/- mice a sodium-rich chow (8% NaCl) for 24 weeks (pg. 42, “Study 1: effect of salt on atherosclerosis”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to combine the high salt diet taught by Johansson with the high cholesterol diet taught by Chatterjee and Cao by adding the sodium-rich chow taught by Johansson to the diet taught by Chatterjee and Cao with a reasonable expectation for success. An artisan would have a reasonable expectation of success because both Johansson and Chatterjee and Cao are directed to using animal models of atherosclerosis and providing a high salt or high cholesterol diet to induce atherosclerosis [e.g., 0177 of Chatterjee] (Objectives of Johansson). One would be motivated to modify the method of Chatterjee and Cao to include added sodium because as taught by Johansson, a high-salt diet with fixed high Ang II levels synergistically affects the acceleration of atherosclerosis, and exposing animals to different salt diets allows one to explore the effects of salt on the atherosclerotic process (pg. 45, “Discussion”, paras 1 and 2).
Response to Arguments
Applicant's arguments filed 04/08/2026 have been fully considered but they are not persuasive.
In response to applicant's argument that the recitation of “for treatment of a vascular disease” in the preamble of claim 84 is “necessary to give life, meaning, and vitality” to the claim, and that the Examiner incorrectly asserts that “ [a] recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.”, the quotation referenced by the Examiner is cited directly from the MPEP, specifically MPEP § 2111.02.II. The Applicant fails to provide evidence or explain how this reference is an incorrect assertion.
Further, the Applicant cites Gilead Sciences, Inc. to support their argument that the preamble is limiting. However, the preamble from Gilead Sciences, Inc. recites a method of treatment/a method with an expected outcome from the method steps (e.g., to protect a primate host from a self-replicating infection). The preamble of instant claim 84 is related to a method of screening, not a method of treatment. It is unclear how the recitation of “A method of screening a therapeutic agent for treatment of a vascular disease” claims a “positively recite[d] efficacy limitation” as in Gilead Sciences, Inc. The Board in this case also noted that “protection” was a key in the patent’s prosecution and not necessarily an inherent result. The instantly recited preamble does not require a similar result (e.g., the therapeutic agent is not required to treat vascular disease). Additionally, if the prior art teaches the same claimed method steps, why would the prior art not then be able to screen a therapeutic agent for treatment of a vascular disease? What about the preamble further limits the structure (e.g., active method steps) of the claims?
In kind, the statement of claim 112 being objected to if claim 84 is found allowable stands.
The Examiner notes however, in response to applicant's argument that Chatterjee is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Chatterjee is analogous art due to studying the effect of a high cholesterol diet on a subject and various interventions.
Additionally, in response to Chatterjee dealing with a different problem to be solved, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Further, Chatterjee does teach vasculitis, a vascular disease, as one of the diseases being investigated and treated (e.g., claim 6 of Chatterjee). With this consideration, the Applicant fails to distinctly point out the criticality of the percentage of cholesterol and cocoa butter in the high cholesterol diet used in Chatterjee. The Applicant refers to studying late-stage vascular diseases, but this feature is not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The Applicant argues that “it is well known that it takes time for a high cholesterol diet to induce, e.g., atherosclerotic pathology” and that “significantly increasing the percentage of cholesterol in the diet by over three times and prolonging the high cholesterol dietary condition prior to administration of a therapeutic agent pursuant to the present claims better induces the pathology for vascular disease when compared to previous and current model”. However, the Applicant fails to provide any evidence from the prior art to support this statement.
In response to applicant's arguments against the references individually, such as Johansson and Cao, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
No claims are allowed.
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ALLISON M. JOHNSON
Examiner
Art Unit 1638
/ALLISON MARIE JOHNSON/Examiner, Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
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