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 .
Detailed Action
Request for Continued Examination
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/19/2026 has been entered.
Response to Amendments
The amendments to the claims submitted 12/22/2025 have been entered.
In view of the amendments made, the 103 and 102 rejections made in the office action of 10/20/2025 have been withdrawn. However, on further consideration, new grounds of rejection are introduced.
Status of Claims
Claims 53-79 are currently pending.
Claims 63, 67, 72-73, and 75 are withdrawn.
At examiner’s discretion, search and examination was expanded to include all thiol isomerases of claims 54, 55, and 56.
Claims 56 and 78-79 have been rejoined.
Claim Interpretation
Claim 53 is drawn to a method of inhibiting thiol isomerase. The limitation “inhibiting a thiol isomerase” is an inherent property. Any instance where a galloylated polyphenol has been administered would read on the instant claims as the compounds have the property of the inhibiting thiol isomerases as shown by the instant disclosure.
New Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 53-60, and 76-77 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Zhao (US 8,039,510, published 2011).
Zhao in col. 14-15, Example 1 discloses methods of isolating and preparing compositions comprising Theaflavin-3-gallate and Theaflavin-3,3’-digallate. Zhao in col. 15, Example 2 discloses methods of isolating and preparing compositions comprising, individually, theaflavin-3-gallate or theaflavin-3,3’-digallate. Zhao in col. 16, Example 4 and Table 1 discloses administration of “pure theaflavin” in dosages of 1-4 mg/kg/day. Administered theaflavins include theaflavin-3-gallate (TF2-A2) and theaflavin-3,3’digallate (TF3-2).
Claim(s) 53-55 and 78 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Wen (Molecules, 2023, 28, 4856, published June 2023).
Wen in sec. 6 Safety Profile and Pharmacokinetics of PGG discloses administration of pentagalloyl-glucose (PGG) in doses of 100 or 200 mg/kg/day to determine safety.
Claim(s) 53-55 and 79 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Hsu (British Journal of Nutrition, 2007, 98, 727-735)
Hsu in its abstract discloses administration of gallic acid in dose levels of 50 and 100 mg/kg to rats for a period of 10 weeks.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 53-62, 64-66, 68-71, 74, and 76-79 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhao (cited above) in view of Wen (cited above), Hsu (cited above), Bekendam (Basic & Clinical Pharmacology & Toxicology, 2016, 199, 42-48), Stopa (JI Insight, 2017;2(1)), Pottier (Thrombosis Research, 124, 2009, 468-476), Engbers (Journal of Thrombosis and Haemostasis, 12, 290-296, 2013), and Bertina (Thromb. Haemost. 1999; 82(02): 601-609).
Discussion of Zhao, Wen, and Hsu from the 102 rejections above is incorporated here.
Zhao, Wen, and Hsu do not explicitly teaches or discuss administration of the galloylated polyphenols in patients and/or subjects having venous thrombosis and/or arterial thrombosis, any of the conditions in claim 62, is at risk for venous thrombosis and/or arterial thrombosis, at risk of any of the conditions in claim 66, wherein the subject at risk of thrombosis has had one or more heart valve replacement surgeries, has been previously diagnosed with one or more of a blood clot, blood clotting disorder, atrial fibrillation, or cancer, or wherein the subject has been immobilized for a prolonged period of time.
This is addressed by the combination of Bekendem, Stopa, Pottier, Engbers, and Bertina.
In regards to claims 60-62 Bekendam on p. 45 sec. Blocking PDI activity in Thrombotic Disease states “The observation that PDI serves an essential role in thrombus formation raises the possibility that inhibition of PDI could prevent thrombosis, which occurs in the setting of myocardial infarction, stroke, peripheral arterial occlusive disease, pulmonary embolism and deep vein thrombosis.” In this same section, Bekendam states “In a laser-induced mouse model of thrombus formation, quercetin-3-rutinoside blocked platelet accumulation and fibrin formation at concentrations as low as 0.5 mg/kg.”
While Bekendam is drawn to the effects of quercetin-3-rutinoside, Bekendam at least establishes that inhibition of PDI can lead to antithrombotic results. Considering this, the combination of Paglia and Bekendam at least makes obvious a method of inhibiting a thiol isomerase comprising administering punicalagin to a patient in need thereof.
In regards to claims 58 and 59, Stopa on p. 1, para 1 states “Inhibition of PDI by either monoclonal antibodies or small-molecule inhibitors prevents both platelet formation and fibrin formation at sites of vessel injury.
Additionally, Stopa on p. 2 states “The administration of quercetin-3-rutinoside similarly inhibited thrombus formation following vascular injury in mouse models of thrombosis. Quercetin-3-rutinoside blocks PDI activity by binding to the substrate-binding pocket on PDI and inducing a conformational change in the enzyme, which results in a more compact molecular envelop and reduces substrate binding.”
Regarding claims 64-66 and 68-71, and 74 Pottier, Engbers, and Bertina discuss the connection between blood clots and/or surgery with deep vein thrombosis.
Pottier on p. 468, sec. Introduction states “Based on pathophysiological arguments, immobilization has been suspected of being a risk factor for venous thromboembolism (VTE).” Pottier on p. 475, sec. Conclusions states “This systematic review and meta-analysis suggest that the risk of VTE is approximately doubled in medical bedridden patients even if this result might be overestimated.”
Engbers on p. 293, sec. Results states “Overall, hospitalization was associated with a greater than 7-fold increased risk of venous thrombosis. Engbers continues “Among the cases hospitalized within the 3 months before the index date, 79 of the 126 (65%) had surgery during the hospital admission.” In the same section, Engbers states “Thirty-one (7.8%) of the cases and [four] (0.9%) of the control subjects underwent lower extremity surgery, indicated that lower extremity surgery was associated with an almost 9-fold increased risk of thrombosis…”.
Regarding claim 71, Bertina in its introduction states “A diagnosis of venous thrombosis is made each year in about 0.1% of Western populations. In the majority of cases, the diagnosis is based on objective evidence for an obstruction of the circulation by a blood clot that either formed locally or developed elsewhere in the circulation.”
The MPEP section 2112 states:
A REJECTION UNDER 35 U.S.C. 102 AND 103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. "There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102." In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. Therefore, a 35 U.S.C. 102 and 103 rejection is appropriate for these types of claims as well as for composition claims.
The instant disclosure in figures 13A, 14A, and 14B indicate that gallic acid, theaflavin-3-gallate, theaflavin-3,3’-diagallate, and pentagalloyl glucose inhibit the thiol isomers PDI, ERp57, and Erp5 to some degree. As stated above, the ability to inhibit the claimed thiol isomerases is a property of the compound themselves. Therefore, one of ordinary skill in the art would recognize that administering the galloylated polyphenols would have made the instant claims prima facie obvious at the time of the effective filing date as the thiol isomerase inhibition is a property of the galloylated polyphenols.
Conclusion
No claims allowed.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624