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 .
Claims 1, 3-4 and 6-11 are currently pending.
Priority
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Specification Objections
The disclosure is objected to because of the following informalities:
The amendment filed on December 19, 2024 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: “the entire contents of which are incorporated hereby by reference”. See page 1.
MPEP 211.02(a) states that “When a benefit claim is submitted after the filing of an application, the reference to the prior application cannot include an incorporation by reference statement specifying of the prior application unless an incorporation by reference statement specifying of the prior application was presented upon filing of the application. See Dart Indus. v. Banner, 636 F.2d 684, 207 USPQ 273 (C.A.D.C. 1980). An incorporation by reference statement added after an application’s filing date is not effective because no new matter can be added to an application after its filing date (see 35 U.S.C. 132(a) ).”
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The instant application is a 371 application which has an International filing date of June 20, 2023. The incorporation by reference statement is being added by way of a Preliminary Amendment filed on December 19, 2024, which is after the instant application’s International filing date. Therefore, the “incorporation by reference” statement being added is deemed new matter.
Applicant is required to cancel the new matter in the reply to this Office Action.
Objection to Abstract
Applicant is reminded of the proper content of an abstract of the disclosure. In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class.
In the instant case, the abstract does not include the salts that are currently claimed. Appropriate correction is required.
Claim Objections
Claims 1, 3-4 and 6-11 are objected to for the following reasons:
The phrase 1,5-naphthalenedisulfonate of a compound represented by formula (I) is unclear. The phrase should be amended to recite “1,5-naphthalenedisulfonate salt of a compound represented by formula (I)”.
The phrase hydrochloride of a compound represented by formula (I) is unclear. The phrase should be amended to recite “hydrochloride salt of a compound represented by formula (I):
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 4, 7, 9 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 10 recites a method for treating “disease related to NHE-mediated antiport of a sodium ion or a hydrogen ion”. The specification does not unambiguously define this term, or clearly sets forth the diseases encompassed. While certain diseases are broadly mentioned in the specification and claimed in claim 11, the specification does not define a “disease related to NHE-mediated antiport of a sodium ion or a hydrogen ion” to clearly delimit the patient population encompassed. Further, this term does not have a commonly understood and accepted meaning and thus, the metes and bounds of the claim is unclear.
Claim 4 recites the limitation "the feeding molar ratio". There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitation "the feeding molar ratio". There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the feeding molar ratio". There is insufficient antecedent basis for this limitation in the claim.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4 and 6-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to the (1,5-naphthalenedisulfonate)n salt of the compound of formula (I) wherein n = 0.9-2.0, and the (HCl)m salt of the compound wherein m= 1.6-4.2, or 1.6-2.5, or 3.8-4.2, and a process for making the same.
35 U.S.C. § 112(a) and the first paragraph of pre-AIA 35 U.S.C. § 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111,1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description"). The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert, denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaffv. Wells Bees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); EliLilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm.,927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). An application specification may show actual reduction to practice by describing testing of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the lack of a representative number of species that characterizes the entire claimed genus coupled with the lack of description for how to particularly make the solid salts with the claimed ratios.
In the specification, a molar ratio of 1,5-naphthalenedisulfonate to compound (I) of 1:1 was used to make the salt (see pages 32-33). The two examples describe the process to have made a solid 1,5-naphthalenedisulfonate salt having a 1:1 ratio and a 0.9:1 ratio (salt/compound).
A molar ratio of HCl to compound (I) of 4:1 and 2:1 was used to make the solid HCl salt (see pages 32-35). When a molar ratio of HCl to compound (I) of 4:1 was used, the conditions provided a product with 2.1:1 of HCl to compound (I). See Example 4. The same example discloses to have made a salt with a ratio of 1.6:1 of HCl to compound (I), however, it does not disclose the initial molar ratio of HCl to compound (I) used in the reaction. In addition, the same example discloses to have made the tetrahydrochloride salt of compound (I), however, it does not describe the initial molar ratio of HCl to compound (I) used and necessary to make the tetrahydrochloride salt.
The (HCl)m salt of the compound is claimed to have ratios in which m is selected from
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In the instant specification there is no disclosure of these solid salts in which m is 1.7, 1.8, 1.9, 2.0, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0 and 4.2. In addition, while applicant stated that they have made a tetrahydrochloride salt in example 4 which is said to have a molar ratio of 4.15:1, the process of making it has not been fully described. The process does not describe the initial molar ratio of HCl to compound (I) used and necessary to make the tetrahydrochloride salt.
The (1,5-naphthalenedisulfonate)n salt of the compound is claimed to have ratios in which n is selected from 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, and 2.0. There is no disclosure of these solid salts in which n is 1.0, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, and 2.0. Clearly, reacting a particular molar ratio does not set out that the particular molar ratio of the solid salt will be obtained.
The specification does not provide a method for controlling the salt to compound ratio for the solid state products described in this application.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, states that Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc), the Federal Circuit noted the importance of an application's disclosure and stated, “the hallmark of written description is disclosure.” A disclosure adequately describes an invention when it “reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Id. at 1351. “A ‘mere wish or plan' for obtaining the claimed invention is not adequate written description.” Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348 (Fed. Cir. 2011).
The state of the art is that “chemical reactions are known as unpredictable”. In re Marzocchi, et al., 169 USPQ 367, 370 (CCPA 1971); In re Fisher, 166 USPQ 18, 24 (CCPA 1970). Hence, the need for greater disclosure.
The issue is whether a person skilled in the art would understand applicant to have invented, and been in possession of, the invention as broadly claimed. Thus, the specification does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Not every piece of prior art found in the search has been applied against the instant claims. See MPEP 904.03.
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.
Claims 1, 8, 9-11 are rejected under 35 U.S.C. 103 as being obvious over Guo et al. (US20240082406) in view of Swarbrick et al. (Encyclopedia of Pharmaceutical Technology 13 (Marcel Dekker, NY 1996) pages 453-499) or Bastin et al., (Organic Process Research & Development 2000, 4, 427-435) or Stahl et al. (eds., Handbook of pharmaceutical salts. Properties, selection and use (Wiley-VCH, 2008), pages 265-327) and their combinations.
Applicant claims the HCl salt or napsylate (1,5-naphthlalene disulfonate) salt of the compound of formula
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Determining the scope and content of the Prior art (MPEP §2141.012)
Guo teaches compounds for the treatment of, for example, irritable bowel syndrome or chronic kidney disease, in which the compounds inhibit NHE-mediated reverse transport of sodium or hydrogen ions in a subject. See claims 18 and 19. Particularly, Guo teaches compound represented by the following formula
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at Table 8, and pharmaceutically acceptable salts thereof. See also claim 17, page 73.
A pharmaceutically acceptable salt thereof of the compounds is as follows:
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. Processes for making the salts and, in particular, the hydrochloride salt of the compounds were described as follows:
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Swarbrick specifically discusses that salt formation is a simple chemical manipulation performed to alter the physicochemical, formulation, biopharmaceutical and therapeutic properties of a drug without modifying the basic chemical structure. Swarbrick particularly discussed salt formation to improve drug solubility. Swarbrick teaches that Anionic Pharmaceutical Salt Forms Currently in Use include hydrochloride, napadisylate, etc. See Table 1, pages 454-455. The salts in Swarbrick have a ratio of 1:1 unless their name says otherwise. See that Table 1 has also dihydrochloride, and other di- or bi-salts.
Bastin et al., mentions hydrochloride and napsylate as common pharmaceutical salt-formers (Table 1, p. 428) and discusses specific factors to be considered for salt selection (greater water solubility, less toxicity, or a slower dissolution rate- at right column of page 2).
Stahl et al. discusses commonly used pharmaceutically acceptable salts with specific drugs (example) and properties of such salts. Napththalene-1,5-disulfonic acid and HCl are known salt-formers (p. 296).
Ascertainment of the Difference Between the Prior Art and the Claims
(MPEP §2141.012)
The difference between the claims and the prior art is that applicants are claiming a different salt of an old drug.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The skill level in the art of salt selection is high, as seen in the references cited above. It would have been obvious for one of ordinary skill in the art to form the hydrochloride (mono or di) pharmaceutically acceptable salt and napadisylate (mono) pharmaceutically acceptable salt of the known active compound of Guo et al. because hydrochloride and napadisylate are commonly known and currently used to form pharmaceutically acceptable salts.
Because typical problems encountered in drug development includes insufficient solubility, etc., a person of ordinary skill in the art would be highly motivated to make said claimed salts of the abovementioned compound to optimize the pharmacological profile of the compound, especially when salt formation is a commonly known technique used by a person of ordinary skill in the art in order to increase drug solubility. The motivation derives from the “normal desire of scientists or artisans to improve upon what is already generally known." In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003).
The factual situation is thus largely the same as in Pfizer, Inc. v. Apotex, Inc. 82 USPQ2d 1321, which was directed to the amlodipine besylate drug. One of ordinary skill in the art would look in pharmacopeias and compendia to find an anion having precedence for use within the pharmaceutical industry and to try salts from the known list. The secondary references above provide a reasonable expectation of success in making and using the claimed salts for the same use taught by the reference Guo.
In addition, the artisan would have been highly motivated to prepare the hydrochloride salt of compound D1-P1-S of Guo because they taught how to make them. By following the process taught in Guo to prepare the hydrochloride salt, which has the same steps of the process claimed in claim 8 (HCl/methanol), the hydrochloride salt of D1-P1-S in which m2 is as claimed would have been obtained. A process using the same ingredients and steps would be expected to provide the same product. Claim 8 would have been obvious.
Regarding claim 9, it would have been obvious to run the reaction under a nitrogen atmosphere to exclude oxygen and moisture from the reaction environment, which can otherwise cause unwanted chemical changes.
Conclusion
Claims 1, 3-4 and 6-11 are rejected. No claim is in condition for allowance.
Not every piece of prior art found in the search has been applied against the instant claims. See MPEP 904.03.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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