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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/02/2026, were in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents were considered. A signed copy of Form PTO-1449 is enclosed herewith.
Status of the Claims
Claims 1-4 and 6-30 are pending.
Applicants’ arguments filed on 07/02/2026, 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 Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn.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 of rejections and/or objections presently being applied to the instant application.
Applicants’ amendments, filed on 07/02/2026, have each been entered into the record. Applicants have amended claims 1-4. Applicants have newly added claims 20-30. Claims 7-19 remain withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected invention. Therefore, claims 1-4, 6 and 20-30 are the subject of the Office action below.
Withdrawn Rejections:
The rejection of claims 1-4 and 6 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is overcome by the Applicants’ amendments and is hereby withdrawn. For example, claim 1 has been amended so that claim 1 no longer recites “less than about 1%”.
Claim Rejections - 35 USC § 103
Maintained/New Grounds of Rejection, Necessitated by Applicant’s Amendments
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.
The rejection of claims 1-4 and 6 is maintained and newly added claims 20-30 are rejected under 35 U.S.C. 103 as being unpatentable over Bharadwaj of record (Oncotarget, 2016) in view of: 1) Minus of record (Org. & Biomol Chem., 2020, 18, 3288-3296); 2) Fu of record (Org. Biomol. Chem., 2019, 17, 9994-9998); 3) Tweardy of record (WO2019204427A1); and 4) Basak of record (Advanced Drug Delivery Reviews, 2007), for the reasons of record set forth in the previous office action, of which said reasons are herein reiterated.
By way of a background, Applicants’ invention (see e.g., ¶s 00033-00043 of the specification), is drawn to a composition comprising compound of formula (I):
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(also known as TTI-101, see ¶ 000150 of the specification); and substantially free of an impurity selected from the group consisting of a compound of formula (II):
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, a compound of formula (III):
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, and a compound of formula (IV):
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, or a combination thereof.
The specification discloses working examples showing:
a) presence of impurity compound 6 (a compound of formula (II)), during: i) synthesis of compound TTI-101 (see ¶s 000150-000155 of the specification); or ii) recrystallization of compound TTI-101 (see ¶s 000156-000166 of the specification).
b) depending on the storage condition, presence of impurity compound 6 (a compound of formula (II)), or presence of impurity compound 6 (a compound of formula (II)) and impurity compound of formula (IV), during storage of compound TTI-101 (see ¶s 000167-000171 of the specification).
Independent claim 1 directed to a composition comprising:
a) at least 98% area by HPLC of TTI-101;
b) >0 and ≤ 1% area by HPLC of a compound of formula (II); and
c) >0 and ≤ 0.2% area by HPLC of a compound of formula (IV).
Independent claim 20 is similar to claim 1, however, claim 20 requires a composition that does not comprise a detectable amount of a compound of formula (III).
Independent claim 21 is similar to claim 1, however, claim 21 requires a product by process.
Claim 6 is drawn to a pharmaceutical composition comprising a composition of claim 1 and a pharmaceutically acceptable carrier.
Claim 6 does not specify a particular carrier, but it does reads on a carrier. Accordingly, for the purpose of examination, any carrier that is employed in the formulation of a pharmaceutical composition comprising a composition of claim 1, is included in the interpretation of “a pharmaceutically acceptable carrier”.
Regarding claims 1-4, 6 and 20, Bharadwaj teaches a pharmaceutical composition comprising TTI-101 (C188-9, see, e.g., Table 1) and a pharmaceutically acceptable carrier. TTI-101 is a STAT3 inhibitor, which was found to inhibit the growth of radioresistant head and neck squamous cell carcinoma (HNSCC) in mice HNSCC xenograft. Please see abstract, Figures 1-5, Tables 1-3 and “Materials AND METODS” section. Bharadwaj did not teach compound of formula (III) in a composition.
Although Bharadwaj is not explicit in disclosing a trace amount of an impurity, in the composition, a person skilled in the art would have reasonably expected that a pharmaceutical composition comprising TTI-101, would comprise a trace amount of an impurity (e.g., >0 and ≤ 1% area by HPLC), in the composition. This is because at the time of the instant invention:
TTI-101 was known to be susceptible to oxidative degradation.
stability of compound TTI-101 can be enhanced under certain conditions.
3) FDA allow for certain trace levels of impurities in drugs, and determination of the limits for the trace levels of impurities is a routine activity in the pharmaceutical art.
For example:
1a) Minus teaches that significant oxidative decomposition of TTI-101 (C188-9) to iminoquinone compound (which is identical to Applicants’ impurity compound of formula (II), see discussions above), was observed within 4 hours in aqueous buffer (a pharmaceutically acceptable carrier). Please see Minus at ¶ on left column of page 3292, Figure S1 and Scheme 1 illustration below for illustration:
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Minus discloses that the 1,4-substitution pattern of hydroxyl-naphthalene sulfonamides renders the core structure susceptible to oxidation. Some synthetic intermediates indeed proved quite prone to air oxidation and subsequent decomposition. Please see ¶ on left column of page 3292. Minus (see page 3288), also discloses TTI-101 as STAT3 inhibitor with a known utility as an anticancer agent.
1b) Furthermore, N-arylsulfonamide compounds are also susceptible to oxidation, generating corresponding quinone imine and quinone compounds similar to compound (II) and compound (IV). For example, similar to Minus (see discussions above), Fu (see page 9996, Scheme 2), also teaches oxidation of N-arylsulfonamide compound 1a:
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Accordingly, at the time of the instant invention, one skilled in the art would have envisaged the susceptibility of an N-arylsulfonamide compound (e.g., TTI-101) to oxidation, generating a quinone imine compound of formula (II) and a quinone compound of formula (IV):
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, from the Minus and Fu disclosures.
2) Tweardy at ¶ 00276, states:
“A batch of compound of Formula IIIx was stored in Teflon Bags (5 mil PFA; 5" x 4"; Welch Fluorocarbon, Inc., Part Number (PN) P-00014-1), using plastic tie strips under two conditions: 25 °C/65% RH and 40 °C/75% RH. The results show that under both conditions, compound of Formula IIIx maintained white powder appearance after three months. Additionally, after three months, the purity of compound of Formula IIIx by HPLC remained at 100% AUC under both conditions.” Emphasis added.
Similar to the Minus (see discussions above), Tweardy (see page 77), also teaches a working example of obtaining compound III (i.e., Applicants’ claimed compound of formula (II)), from the oxidation of compound IIIx (i.e., TTI-101), which confirms the prior art knowledge that TTI-101, is susceptible to oxidation (see discussions above).
3) Basak discloses that FDA allow for certain trace levels of impurities in both drug substance and product. Please see abstract and §s 1-8. Drug substance impurities threshold could be up to 1%, depending on the maximum daily dose and the type of impurity. Please see Tables 1-2. The nature and the quantity of these impurities is governed by a number of different factors, including synthetic route of the drug substance, reaction conditions, quality of the starting material of the drug substance, reagents, solvents, purification steps, excipients, drug product manufacturing processes, packaging, and storage of the end product. Emphasis added, please see § 3.
The separation methods include thin layer chromatography (TLC), high performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrophoresis (CE). HPLC is the most commonly used method for impurity monitoring in an inexpensive way. Please see § 4.
Therefore, at the time of the instant invention, it would have been obvious to one skilled in the art to employ conditions that would, for example, reduce oxidation of TTI-101 at the OH-aryl bond and N-aryl bond, in order to generate a quinone compound of formula (II) and a quinone compound of formula (IV), with a reasonable expectation of limiting the level of impurities to within the threshold of, for example, >0 and ≤ 1% area by HPLC. Please see discussions above.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
The threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed impurity compound of formula (II) and impurity compound of formula (IV), is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art (see discussions above).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality (emphasis added) has been demonstrated in the specification with regard to the claimed threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed compound of formula (II) and compound of formula (IV).
Regarding claims 21-30, the cited prior art (see discussions above), combine to disclose a composition comprising:
a) at least 98% area by HPLC of TTI-101;
b) >0 and ≤ 1% area by HPLC of a compound of formula (II); and
c) >0 and ≤ 0.2% area by HPLC of a compound of formula (IV).
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). "The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product”. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983). See MPEP 2113.
In the instant case, the cited prior art (see discussions above), combine to disclose a composition. Therefore, claims 1-4, 6 and 20-30 are obvious over Bharadwaj, Minus, Fu, Tweardy and Basak.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited reference. Therefore, the invention as a whole was prima facie obvious at the time it was made.
Response to Applicants’ Arguments
Applicants raised several arguments (see pages 10-18 of Remarks), alleging that instant claims are non-obvious over the cited prior art on the grounds that:
1) the combination of the cited references fails to disclose the claimed composition components with the distinct threshold (see page 11 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive, because the threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed impurity compound of formula (II) and impurity compound of formula (IV), is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art (see discussions above).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality (emphasis added) has been demonstrated in the specification with regard to the claimed threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed compound of formula (II) and compound of formula (IV).
2) the cited prior arts (see page 11 of Remarks), fail to address the limitation of to a composition comprising:
a) at least 98% area by HPLC of TTI-101;
b) >0 and ≤ 1% area by HPLC of a compound of formula (II); and
c) >0 and ≤ 0.2% area by HPLC of a compound of formula (IV).
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive, because all the claim elements recited the amended claim 1 have been addressed in the new grounds of rejection set forth in the discussions above. The Examiner, therefore, applies the same reasons hereto.
3) Bharadwaj fails to disclose or suggest any impurity amounts for TTI-101 (see page 11 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive, because Bharadwaj was cited for teaching a pharmaceutical composition comprising TTI-101 (see discussions above). The Office did not take the position that Bharadwaj teaches any impurity amounts for TTI-101.
4) Minus and Tweardy fail to disclose >0 and ≤ 1% area by HPLC of a compound of formula (II). Please see page 11 of Remarks.
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive, because the reasons for the Office’s reliance on the Minus and Tweardy references, in order to reject the instant claims, are set forth in the discussions above. The Examiner, therefore, applies the same reasons hereto. It is also noted that Tweardy (see page 77), also teaches a working example of obtaining compound III (i.e., impurity compound of formula (II)), from the oxidation of compound IIIx (i.e., TTI-101), which confirms the prior art knowledge that TTI-101, is susceptible to oxidation (see discussions above). The threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed impurity compound of formula (II), is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art (see discussions above).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality (emphasis added) has been demonstrated in the specification with regard to the claimed threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed compound of formula (II).
5) Basak fails to disclose or suggest TTI-101 or an impurity compound for TTI-101 (see pages 11-12 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive, because Basak was cited for disclosing that FDA allow for certain trace levels of impurities in both drug substance and product. Drug substance impurities threshold could be up to 1%, depending on the maximum daily dose and the type of impurity. The nature and the quantity of these impurities is governed by a number of different factors, including synthetic route of the drug substance, reaction conditions, quality of the starting material of the drug substance, reagents, solvents, purification steps, excipients, drug product manufacturing processes, packaging, and storage of the end product. Emphasis added, please see discussions above.
6) Applicants argue (see page 12 of Remarks), against the Fu reference on the grounds that: i) Fu’s compound is structurally unrelated to compound TTI-101; and ii) Fu does not disclose >0 and ≤ 0.2% area by HPLC of a compound of formula (IV).
Response:
Fu was cited for disclosing the susceptibility of an N-arylsulfonamide compound to oxidation, generating quinone imine compound and quinone compound (see discussions above). The threshold of, for example, >0 and ≤ 0.2% area by HPLC, for the claimed impurity compound of formula (IV), is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art (see discussions above).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality (emphasis added) has been demonstrated in the specification with regard to the claimed threshold of, for example, >0 and ≤ 0.2% area by HPLC, for the claimed compound of formula (IV).
7) One skilled in the art would not have had a reasonable expectation of success in combining the cited references because the cited references individually or in combination fails to disclose or suggest how to arrive at a composition comprising TTI-101, a compound of formula (II) and a compound of formula (IV), within the claimed composition limitations (see pages 12-17 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive, because the cited references (see discussions above), combine to disclose that:
i) N-arylsulfonamide compounds (e.g., TTI-101) are susceptible to oxidation, generating a quinone imine compound (e.g., compound of formula (II)) and a quinone compound (e.g., compound of formula (IV)).
ii) FDA allow for certain trace levels of impurities in both drug substances and product. Drug substance impurities threshold could be up to 1%, depending on the maximum daily dose and the type of impurity. The nature and the quantity of these impurities is governed by a number of different factors, including synthetic route of the drug substance, reaction conditions, quality of the starting material of the drug substance, reagents, solvents, purification steps, excipients, drug product manufacturing processes, packaging, and storage of the end product. Emphasis added, please see discussions above.
Therefore, at the time of the instant invention, it would have been obvious to one skilled in the art to employ conditions that would, for example, reduce oxidation of TTI-101 at the OH-aryl bond and N-aryl bond, in order to generate a quinone compound of formula (II) and a quinone compound of formula (IV), with a reasonable expectation of limiting the level of impurities to within the threshold of, for example, >0 and ≤ 1% area by HPLC. Please see discussions above.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
The threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed impurity compound of formula (II) and impurity compound of formula (IV), is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art (see discussions above).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality (emphasis added) has been demonstrated in the specification with regard to the claimed threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed compound of formula (II) and compound of formula (IV).
8) The claimed invention is not directed to TTI-101 as a compound per se (see pages 12-17 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive, because the Office did not take the position that the claimed invention is directed to TTI-101 as a compound per se.
Furthermore, in response to the Applicants’ arguments against the references individually (e.g., Bharadwaj fails to disclose or suggest any impurity amounts for TTI-101, see e.g., pages 13-16 of Remarks), one cannot show nonobviousness by attacking references individually where the rejections are based on combination of references. In obviousness rejection a combination of references is used, and the references are relied upon in combination and are not meant to be considered separately as in a vacuum. It is the combination of all of the cited and relied upon references that make up the state of the art with regard to the claimed invention. 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).
The rejection of claims 1-4 and 6 is maintained and newly added claims 20-30 are rejected under 35 U.S.C. 103 as being unpatentable over Alibhai of record (U.S. Pub. No. 20210228512, effective filing date 01/248/2020), in view of: 1) Minus of record (Org. & Biomol Chem., 2020, 18, 3288-3296); 2) Fu (Org. Biomol. Chem., 2019); and 3) Basak of record (Advanced Drug Delivery Reviews, 2007), for the reasons of record set forth in the previous office action, of which said reasons are herein reiterated.
The corresponding teachings of Minus, Fu and Basak, are discussed above and hereby incorporated into the instant rejection.
Regarding claims 1-4, 6 and 20, Alibhai (see Example 5 and Table 6), discloses that the compound of formula (I) is susceptible to oxidation and also discloses a composition comprising compound of formula (I) and having a purity of 99.05% by HLPLC. Please see Example 5 and Table 6.
Therefore, at the time of the instant invention, it would have been obvious to one skilled in the art to employ conditions that would, for example, reduce oxidation of TTI-101 at the OH-aryl bond and N-aryl bond, in order to generate a quinone compound of formula (II) and a quinone compound of formula (IV), with a reasonable expectation of limiting the level of impurities to within the threshold of, for example, >0 and ≤ 1% area by HPLC. Please see discussions above.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
The threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed impurity compound of formula (II) and impurity compound of formula (IV), is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art (see discussions above).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality (emphasis added) has been demonstrated in the specification with regard to the claimed threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed compound of formula (II) and compound of formula (IV).
Regarding claims 21-30, the cited prior art (see discussions above), combine to disclose a composition comprising:
a) at least 98% area by HPLC of TTI-101;
b) >0 and ≤ 1% area by HPLC of a compound of formula (II); and
c) >0 and ≤ 0.2% area by HPLC of a compound of formula (IV).
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). "The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product”. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983). See MPEP 2113.
In the instant case, the cited prior art (see discussions above), combine to disclose a composition. Therefore, claims 1-4, 6 and 20-30 are obvious over Alibhai, Minus, Fu and Basak.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited reference. Therefore, the invention as a whole was prima facie obvious at the time it was made.
MPEP 2143(e) states: The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited reference. Therefore, the invention as a whole was prima facie obvious at the time it was made.
Response to Applicants’ Arguments
Applicants argue (see pages 18-19 of Remarks), alleging that instant claims are non-obvious over the cited prior art on the grounds that Alibhai fails to disclose or suggest an impurity compound of formula (II) or an impurity compound of formula (IV) for TTI-101.
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive. This is because, Alibhai was cited for disclosing that TTI-101 is susceptible to oxidation and also discloses a composition comprising TTI-101 and having a purity of 99.05% by HLPLC (see discussions above). Minus, Fu and Basak (see discussions above), combine to disclose that:
i) N-arylsulfonamide compounds (e.g., TTI-101) are susceptible to oxidation, generating a quinone imine compound (e.g., compound of formula (II)) and a quinone compound (e.g., compound of formula (IV)).
ii) FDA allow for certain trace levels of impurities in both drug substances and product. Drug substance impurities threshold could be up to 1%, depending on the maximum daily dose and the type of impurity. The nature and the quantity of these impurities is governed by a number of different factors, including synthetic route of the drug substance, reaction conditions, quality of the starting material of the drug substance, reagents, solvents, purification steps, excipients, drug product manufacturing processes, packaging, and storage of the end product. Emphasis added, please see discussions above.
Accordingly, a composition comprising compound of formula (I), an impurity compound of formula (II) and an impurity compound of formula (IV), from the Alibhai’s disclosures, would have been obvious in view of Minus, Fu and Basak.
The threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed impurity compound of formula (II) and impurity compound of formula (IV), is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art (see discussions above).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality (emphasis added) has been demonstrated in the specification with regard to the claimed threshold of, for example, >0 and ≤ 1% area by HPLC, for the claimed compound of formula (II) and compound of formula (IV).
Non-Statutory Obviousness-Type Double Patenting
Maintained/New Grounds of Rejections Necessitated by Applicants’ Claim Amendments
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
The rejection of claims 1-4 and 6 is maintained and newly added claims 20-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. patent Nos:
11,547.683 (claims 1-19);
11,077,077 (claims 1-19);
11,547,683 (claims 1-19);
11,161,831 (claims 1-15); and
12,053,444 (claims 1-20); and
12,043,640 (claims 1-114),
in view of: 1) Minus of record (Org. & Biomol Chem., 2020, 18, 3288-3296); 2) Fu (Org. Biomol. Chem., 2019); and 3) Basak of record (Advanced Drug Delivery Reviews, 2007), for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
The corresponding teachings of Minus, Fu and Basak, are discussed above and hereby incorporated into the instant rejection.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application and the reference patents are similarly drawn to a compound of formula (I).
For example, the claims of the instant application are drawn to a composition comprising compound of formula (I) and an impurity, whereas, the claims of the U.S. patent No. 11,547,683 (‘683 patent) are directed to a composition comprising compound of formula (I) and a method of using a composition comprising compound of formula (I).
Although the ‘683 patent is not explicit in claiming an impurity in the composition, the ‘683 patent discloses that the compound of formula (I) is susceptible to oxidation and also discloses a composition comprising compound of formula (I) and having a purity of 99.6% by HLPLC. Please see Example 5 and Table 7.
Accordingly, a composition comprising compound of formula (I) and an impurity, from the ‘683 patent embodiment, would have been obvious in view of Minus, Fu and Basak.
Therefore, there is sufficient overlap between the claim scopes to render them obvious over each other. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the reference application subject matter.
The rejection of claims 1-4 and 6 is maintained and newly added claims 20-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. patent application Nos:
17/781,349 (claims 1-15, 19 and 23);
18/842,626 (claims 1-87); and
18/842,628 (claims 1-42),
in view of: 1) Minus of record (Org. & Biomol Chem., 2020, 18, 3288-3296); 2) Fu (Org. Biomol. Chem., 2019); and 3) Basak of record (Advanced Drug Delivery Reviews, 2007), for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
The corresponding teachings of Minus, Fu and Basak, are discussed above and hereby incorporated into the instant rejection.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the above cited patent applications are similarly drawn to a composition comprising compound of formula (I).
For example, the claims of the instant application are drawn to a composition comprising compound of formula (I) and an impurity, whereas, the claims of the U.S. patent application No. 17/781,349 (‘349 application), are directed to a composition comprising compound of formula (I).
Although the ‘349 application is not explicit in claiming an impurity in the composition, the ‘349 application discloses that: i) compound of formula (I) can have a purity of greater than 99% (see ¶ 00071) in a composition according to general safety and purity standard as required by FDA (see ¶ 000181); and ii) compositions comprising compound of formula (I) can also comprise antioxidants to retard oxidation (see ¶ 000167).
Accordingly, a composition comprising compound of formula (I) and an impurity, from the ‘349 application embodiment, would have been obvious in view of Minus, Fu and Basak.
Therefore, there is sufficient overlap between the claim scopes to render them obvious over each other. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the reference application subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicants’ Arguments
Applicants argue alleging that the claimed invention would not have been obvious to a person skilled in the art over the above cited patent applications and above cited patents, for the same reasons argue previously (see pages 19-20 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are found to be persuasive. This is because, the Applicants are reiterating the same arguments which have been addressed (see discussions above). The Examiner, therefore, applies the same response hereto.
Conclusion
No claim is allowable.
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.
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Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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