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 .
Non-Final Rejection
The Status of Claims:
Claims 1-15, 17-21 are pending.
Claims 1-12, 14-15, 17-21 are rejected.
Claim 13 is objected.
DETAILED ACTION
1. Claims 1-15, 17-21 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/CN2023/084726 03/29/2023 which has foreign priority documents CHINA CN202210326113.5 03/29/2022 and CHINA CN202310281376.3 03/21/2023.
Drawings
3. The drawings filed on 9/24/2024 are accepted by the examiner.
IDS
4. The IDS filed on 7/6/26 & 9/24/24 are reviewed by the examiner.
Claim Objections
Claim 13 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
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 2-4, 6-12, 15, 17-21 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 pre-AIA the applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 2 recites the broad recitation " an X-ray powder diffraction pattern comprising diffraction peaks at 26±0.2° diffraction angles of 7.440, 14.87°,15.77°, 17.81°, and 18.61°” and the claim also recites “ preferably, the free base crystalline form A has an X-ray powder diffraction pattern comprising diffraction peaks at 26±0.2° “, diffraction angles of 7.44°,11.14°, 11.36°, 14.87°, 15.77°, 16.97°, 17.81°, and 18.61°”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Similarly, the rest of the claimed limitations in the claim 2 containing the term” preferably” is applied in the same way as shown before.
In the present instance, claim 3 recites the broad recitation " X-ray powder diffraction pattern comprising diffraction peaks at 26±0.2° diffraction angles of 7.21°, 12.48°,13.17°,14.41°, 19.09°, 19.56°, 22.09°, and 26.49°” ; and the claim also recites “preferably, the free base crystalline form B has an X-ray powder diffraction pattern
comprising diffraction peaks at 28±0.2° diffraction angles of 7.21 °, 12.48°, 13.17°, 14.41 °,16.72°, 19.09°, 19.56°, 20.90°, 22.09°, and 26.49° “, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Similarly, the rest of the claimed limitations in the claim 3 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 4 recites the broad recitation “ the pharmaceutically acceptable salt of the compound of formula I”; and the claim also recites “preferably, the pharmaceutically acceptable salt of the compound of formula I is a hydrochloride, a maleate, a p-toluenesulfonate, a benzenesulfonate, or a malonate of the compound of formula I”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In the present instance, claim 6 recites the broad recitation “ the crystalline form A of hydrochloride has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2° diffraction angles of 7.77°, 9.01 °, 10.10°, 15.54°, 17.51 °, 19.24°, and 24.49° ” ; and the claim also recites “preferably, the crystalline form A of hydrochloride has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2° diffraction angles of 7.77°, 9.01 °, 10.10°, 15.54°, 17.51 °, 18.01 °, 19.24°, 20.05°, 21.28°, 23.38°, 23.79°, 24.49°, 26.07°, and 28.33°”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Similarly, the rest of the claimed limitations in the claim 6 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 7 recites the broad recitation “ the crystalline form A of hydrochloride has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2° diffraction angles of 7.77°, 9.01 °, 10.10°, 15.54°, 17.51 °, 19.24°, and 24.49° ” ; and the claim also recites “preferably, the crystalline form A of hydrochloride has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2° diffraction angles of 7.77°, 9.01 °, 10.10°, 15.54°, 17.51 °, 18.01 °, 19.24°, 20.05°, 21.28°, 23.38°, 23.79°, 24.49°, 26.07°, and 28.33°”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Similarly, the rest of the claimed limitations in the claim 7 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 8 recites the broad recitation “the crystalline form A of ptoluenesulfonate has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2°diffraction angles of 4.99°, 7.26°, 8.70°, 8.87°, 15.40°, 17.73°, 21.01 °, and 24.13°” ; and the claim also recites “preferably, the crystalline form A of p-toluenesulfonate has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2° diffraction angles of 4.99°, 7.26°, 8.70°, 8.87°, 15.20°, 15.40°, 16.68°, 17.73°, 19.71 °, 21.01 °, and 24.13° ”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Similarly, the rest of the claimed limitations in the claim 8 containing the term” preferably” are applied in the same way as shown before. ”
In the present instance, claim 9 recites the broad recitation “the crystalline form A ofbenzenesulfonate has an X-ray powder diffraction pattern comprising diffraction peaks at28±0.2° diffraction angles of 5.36°, 7.28°, 8.34°, 9.64°, 16.20°, 18.55°, and 21.49°” ; and the claim also recites “preferably, the crystalline form A of benzenesulfonate has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2° diffraction angles of 5.36°, 7.28°, 8.34°, 9.64°,16.20°, 18.55°, 19.28°, 21.49°, 21.81 °, 23.21 °, 25.05°, and 25.74°”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Similarly, the rest of the claimed limitations in the claim 9 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 10 recites the broad recitation “the crystalline form A of malonate has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2°diffraction angles of 6.75°, 9.96°, 10.67°, 14.48°, 16.04°, 16.88°, 18.04°, and 18.29°” ; and the claim also recites “preferably, the crystalline form A of malonate has an X-ray powder diffraction pattern comprising diffraction peaks at 28±0.2° diffraction angles of 5.34°, 6.75°, 9.96°, 10.67°, 11.83°, 13.49°, 14.48°, 16.04°, 16.88°, 17.04°, 18.04°, 18.29°, and 27.38°
”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Similarly, the rest of the claimed limitations in the claim 10 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 11 recites the broad recitation “a pharmaceutically acceptable salt of the compound of formula I” and the claim also recites “ preferably, the pharmaceutically acceptable salt of the compound of formula I is a hydrochloride, a maleate, a p-toluenesulfonate, a benzenesulfonate, or a malonate of the compound of formula I”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In the present instance, claim 11 recites the broad recitation “the compound of formula I with an inorganic acid or an organic acid” and the claim also recites “preferably, the compound of formula I and the acid are in a molar ratio of 5: 1 to 1 :5, such as 3:1, 2:1, 1:1, 1:1.5, 1:2, 1:2.5, or 1:3. preferably, the compound of formula I and the acid are in a molar ratio of 1:1 or 2:1. ”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 11, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 12 recites the limitation " preferably, the humidity of the system is 15%-100% RH;" in lines 43. There is insufficient antecedent basis for this limitation in the claim.
In the present instance, claim 12 recites the broad recitation “a saturated salt solution” and the claim also recites “preferably, the saturated salt solution is a saturated inorganic salt solution; preferably, the saturated inorganic salt solution is a saturated potassium acetate solution, a saturated potassium carbonate solution, a saturated sodium bromide solution, or a saturated
potassium bromide solution”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims
Similarly, the rest of the claimed limitations in the claim 12 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 15 recites the broad recitation “ the pharmaceutically acceptable salt thereof”; and the claim also recites “ preferably, the pharmaceutically acceptable salt of the compound of formula I is a hydrochloride, a maleate, a p-toluenesulfonate, a benzenesulfonate, or a malonate of the compound of formula I; preferably, the crystalline form of the salt is the crystalline form A of hydrochloride, the crystalline form A of maleate, the crystalline form A of p-toluenesulfonate, the crystalline form A of benzenesulfonate, or the crystalline form A of malonate of the compound of formula I”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In the present instance, claim 17 recites the broad recitation “ P2X3-related disease ”; and the claim also recites “ preferably, the P2X3-related disease comprises: pain, genitourinary system diseases, or respiratory system diseases;”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Similarly, the rest of the claimed limitations in the claim 17 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 18 recites the broad recitation “ a mobile phase A”; and the claim also recites “ preferably, the mobile phase A is an aqueous solution of 0.05%-0.15% formic acid and 2%-7% acetonitrile, illustratively an aqueous solution of 0.1 % formic acid and 5% acetonitrile”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Similarly, the rest of the claimed limitations in the claim 18 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 19 recites the broad recitation “ the pharmaceutically acceptable salt of the compound of formula I”; and the claim also recites “ preferably, the pharmaceutically acceptable salt of the compound of formula I is a hydrochloride, a maleate, a p-toluenesulfonate, a benzenesulfonate, or a malonate of the compound of formula I”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In the present instance, claim 20 recites the broad recitation “ a P2X3-related disease”; and the claim also recites “ preferably, the P2X3-related disease comprises: pain, genitourinary system diseases, or respiratory system diseases”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Similarly, the rest of the claimed limitations in the claim 20 containing the term” preferably” are applied in the same way as shown before.
In the present instance, claim 21 recites the broad recitation “ a P2X3-related disease”; and the claim also recites “ preferably, the P2X3-related disease comprises: pain, genitourinary system diseases, or respiratory system diseases”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Similarly, the rest of the claimed limitations in the claim 21 containing the term” preferably” are applied in the same way as shown before.
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 17, 20-21 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treating specific diseases, does not reasonably provide enablement for preventing a P2X3 -related disease in a subject.
. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. Applicants are not enabled for preventing any of these diseases. The only established prophylactics are vaccines not of a compound of formula I such as present here. In addition, it is presumed that “prevention of the P2X3 -related disease in a subject” would require a method of identifying those individuals who will develop the claimed conditions before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted. Application/Control Number: 18/881,402 Page 6 Art Unit: 1625
“The factors to be considered [in making an enablement rejection] have been summarized as the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art, and the breadth of the claims”, In re Rainer, 146 USPQ 218 (1965); In re Colianni, 195 USPQ 150, Ex parte Formal, 230 USPQ 546. 1) As discussed above, preventing the disease requires identifying those patients who will acquire the disease before the disease occurs. This would require extensive and potentially opened ended clinical research on healthy subjects. 2)
The passage spanning lines 19-26 on page 17 lists the diseases Applicant intend to treat. 3) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical preventative medicine for the disease and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will become prevented the diseases before the fact. 6) The artisan using Applicants invention would be a Board Certified physician in those diseases with an MD degree and several years of experience. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of any those diseases generally. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent any those diseases generally. That is, the skill is so low that no compound effective generally against any those diseases has ever been found let alone one that can prevent such conditions. 7) It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved", and physiological activity is generally
considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed diseases and on the compounds of formulas (I),(Ibis), (Ia),(Ib),(Ic)
The Examiner suggests deletion of the word “preventing” from the claims.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
5. Claims 1, 4-5, 11,14-15, 17, 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Davenport et al (US 2018/0093980 A1) in view of Silverman ( The Organic Chemistry of Drug Design and Drug Action, Academic Press, Inc. 1992, p.19-21).
Determination of the scope and content of the prior art
Davenport et al discloses crystalline 1,3-thiazol-2-yl substituted benzamide compounds of general fommla (I) to pharmaceutical compositions and combinations comprising the compounds and to the use of the compounds for manufacturing a pharmaceutical composition for the treatment of neurogenic disorders as a sole agent in the followings
A compound of general formula(I):
PNG
media_image1.png
256
390
media_image1.png
Greyscale
(see page 286, claim 1)
One of the examples of formula(I) is
PNG
media_image2.png
292
471
media_image2.png
Greyscale
As in claims 1, 11 (partially) (see page 90 ,compound#72).
Furthermore, it includes all possible crystalline forms, or polymorphs, of the compounds, either as single polymorphs, or as a mixture of more than one polymorph, in any ratio (see page 9, a paeragraph#0129).
20. A pharmaceutical composition comprising a compound
according to claim 1, and a pharmaceutically acceptable
diluent or carrier as in claims 15, 19, .
21. A method of using a compound according to claim 1
for prophylaxis or treatment of a disease, comprising administering an effective an1ount of the compound to a patient in need thereof.
22. The method according to claim 21, wherein said
disease is a genitourinary, gastrointestinal, respiratory, or pain-related disease, condition or disorder; gynecological diseases, dysmenorrhea, dyspareunia, or endometriosis; endometriosis-associated pain as claims 17, 20-21; endometriosis-associated symptoms, dysmenorrhea, dyspareunia, dysuria, or dyschezia; urinary tract disease states associated with bladder outlet obstruction; urinary incontinence conditions, reduced bladder capacity, increased frequency of micturition, urge incontinence, stress incontinence, or bladder hyperreactivity; benign prostatic hypertrophy; prostatic hyperplasia; prostatitis; detrusor hyperreflexia; overactive bladder, symptoms
related-to overactive bladder, increased urinary frequency, urinary urgency, or urge incontinence; urethritis; prostatitis; proctodynia; cystitis; 1d10pathic bladder hypersensitivity; epilepsy; partial generalized seizures; respiratory disorders, chronic obstructive pulmonary disorder (COPD), asthma, bronchospasm. (see page 287, Claims 20-22).
Also, the compounds show high P2X3 receptor inhibition and furthermore selectivity over the P2X2/3 receptor. Selective inhibition of the P2X3 receptor over the P2X2/3 receptor means at least 3-fold selectivity over the P2X2/3 receptor.as in claims 17,20-21 (partially) ( see page 3 ,a paragraph#0036).
In addition, the term "pharmaceutically acceptable salt" refers
to a relatively non-toxic, inorganic or organic acid additionsalt of a compound of the present invention. For example,see S. M. Berge, et al. "Pharmaceutical Salts," J. Pham1. Sci.1977, 66, 1-19. A suitable pharmaceutically acceptable salt
of the compounds of the present invention may be, for
example, an acid-addition salt of a compound bearing a nitrogen atom, in a chain or in a ring, for example, which is sufficiently basic, such as an acid-addition
salt with an inorganic acid, such as hydrochloric, as in claim 14, hydrobromic,
hydroiodic, sulfuric, bisulfuric, phosphoric, or nitric acid, for example, or with an organic acid, such as formic, acetic, acetoacetic, pyruvic, trifluoroacetic, propionic,
butyric, hexanoic, heptanoic, undecanoic, !auric, benzoic, salicylic, 2-( 4-hydroxybenzoyl)-benzoic, camphoric, cinnamic, ethansulfonic, benzenesulfonic, para-toluenesulfonic,methansulfonic, 2-naphthalenesulfonic, naphthalinedisulfonic,
camphorsulfonic acid, citric, tartaric, stearic, lactic,oxalic, malonic, succinic, malic, adipic, alginic, maleic,fumaric, D-gluconic, mandelic, ascorbic, glucoheptanoic,
glycerophosphoric, aspartic, sulfosalicylic, hemisulfuric, or thiocyanic acid (see page 9, a paragraph#0123).
The instant invention, however, differs from the prior art in that the claimed compound having a fluoride attached to substituted phenyl ring is not unspecified in the prior art.
Silverman describes that bioisosterism is a chemical and pharmacological concept where replacing one atom or group of atoms in a molecule with a similar substituent (a "bioisostere") produces broadly similar biological properties (see 19, a section 4). According to Table 2.3, the number 11 shows that hydrogen is equivalent to fluoride (see page 20, Table 2.3, #11).
Ascertainment of the difference between the prior art and the claims
The difference between the instant application and the applied Davenport et al art is that the Davenport et al does not expressly teach the claimed compound having a fluoride attached to substituted phenyl ring
The deficiency of the Davenport et al is cured by the Silverman.
The difference between the instant application and the applied Silvermannin art is that the Silverman does not expressly teach the claimed compound and the method of treating P2X3- related diseases. The deficiencies of the Silverman are cured by the Davenport et al.
Resolving the level of ordinary skill in the pertinent art.
Regarding the instant Claims 1, 4-5, 11, 15, 17, 19-21, with respect to the lack of disclosing the claimed compound having a fluoride attached to substituted phenyl ring
, the Davenport et al prior art is silent about it. However, Silverman does mention that the relationship between hydrogen and fluoride can be bioisosteres which exhibit similar biological properties.
So, if the skilled artisan in the art had desired to replace hydrogen by fluoride on the substituted phenyl as an alternative to hydrogen atom, it would have been obvious to be motivated to do that in order to improve biological properties. This is because the skilled artisan in the art would expect such combined methods to be feasible and successful as guidance shown in the prior art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Davenport et al expressly discloses crystalline 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) including
PNG
media_image2.png
292
471
media_image2.png
Greyscale
to pharmaceutical compositions and combinations comprising the compounds in a pharmaceutical composition for the treatment of a disease, such as neurogenic disorder, as a sole agent.
Whereas Silverman does describe that bioisosterism is a chemical and pharmacological concept where replacing one atom or group of atoms in a molecule with a similar substituent (a "bioisostere") produces broadly similar biological properties.
Although the Davenport et al prior art does not teach that the claimed compound having a fluoride attached to substituted phenyl ring, Silverman does explain
the relationship between hydrogen and fluoride can be bioisosteres which exhibit similar biological properties.
Both prior art are closely related to each other with respect to a known compound in the prior art and the explanation of a slight difference between hydrogen and fluoride attachment on the phenyl ring with similar biological properties.
So, if the skilled artisan in the art had desired to replace hydrogen by fluoride on the substituted phenyl as an alternative to hydrogen atom,
it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to incorporate the teachings of Silverman’s equivalence between hydrogen and fluoride into Davenport’s compound
in order to improve biological properties for the prior compound. This is because the skilled artisan in the art would expect such combined teachings in the prior art to be feasible and successful as guidance shown in the prior art.
Bioisosterism is a chemical and pharmacological concept where replacing one atom or group of atoms in a molecule with a similar substituent (a "bioisostere") produces broadly similar biological properties
So, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to prepare the claimed compound as an alternative in the Townsend et al method. This is because the skilled artisan in the art would expect such a selection and manipulation to be successful and feasible as guidance shown in the prior art.
Mitsuaki expressly discloses the external preparation for treating the parasitic dermatosis, suppressing growth of a parasitic pathogenic organism (= biofilm) or killing the organism and alleviating the inflammation, comprising a vitamin E acetate , a vegetable oil, like olive oil , isopropyl myristate and squalene; similarly, Panin does teach the formulation for topical use comprising, vitamin E acetate, the volatile silicone and hydrogenated castor oil.
Both prior art are commonly related to each other with respect to the formula based on Vitamin E acetate fort treating a skin disease; furthermore, Panin does offer guidance that the use of dimethiconol can increase the tactile sensation of silkiness of the skin.(see col. 2 ,lines 9-20)
So, if the skilled artisan in the art had desired to develop the formula containing at least Vitamin E acetate for the purpose of increasing the tactile sensation of silkiness of the patient’s skin as well as inhibiting the bacterial biofilm more efficiently, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to incorporate the teachings of Panin’s use of dimethiconol along with the volatile silicone and hydrogenated castor oil into the Mitsuaki formula for the skin treatment. This is because the skilled artisan in the art would expect such a combined formula to be successful and feasible as guidance shown in the prior art.
Conclusion
Claims 1-12, 14-15, 17-21 are rejected.
Claim 13 is objected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached 8:00-5:00.
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, Andrew Kosar can be reached at 571-272-0913. 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.
/TAYLOR V OH/Primary Examiner, Art Unit 1625 9/25/2026
