Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claims 13, 19-22, 26, 50-56, 60, 61, 78, 79 and 82-85 are pending in the application. Claims 19 and 21 are rejected. Claims 13, 20, 22, 26, 50-56, 60, 61, 78, 79 and 82-85 are withdrawn from further consideration.
Election/Restrictions
Independent claim 13 does not embrace the elected species of compound. Since the claims are being examined according to MPEP 803.02, examination has been limited to claims embracing the elected species, which are currently only claims 19 and 21. The search and examination of the instant claims has been extended to include the scope of claims 19 and 21 where the disease or condition is hepatocellular carcinoma and the compound being administered is compound 22C, compound 5C or compound 4C, which scope is not allowance.
Response to Amendment / Argument
Objections and rejections made in the previous Office Action have been overcome by Applicant's amendments to the claims. Therefore, arguments pertaining to these objections and rejections will not be addressed.
Claim Rejections - 35 USC § 112(b)
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 19 and 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 19 and 21 recite the limitation "the compound of Formula (I)" in line 1 of each claim. There is insufficient antecedent basis for this limitation in the claim. Parent claim 13 does not define a compound of Formula (I). Claims 19 and 21 have been interpreted as defining the compound recited in step (i) of claim 13.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 19 and 21 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Compounds 22C, 4C and 5C each have a thiophene ring at the position corresponding to RA in parent claim 13, which is not encompassed by the parent claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 19 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over International Application Publication No. WO 2018/161960 A1 by Sun et al. (where an English language version was published as U.S. PGPub No. US 2020/0039995 A1 and will be referred to herein) as evidenced by Yang et al. PLoS ONE, 2016, 11, e0166828.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Sun et al. teach compounds of the following formula for use in the treatment of viral hepatitis B (abstract):
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As particular examples, the prior art teaches the following embodiments on page 37:
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The structures above correspond to the structure of Applicant’s compound 22C with stereochemistry defined except where the thiophene is missing a chloro-substituent. The structure at left corresponds to compound 4C recited in instant claims 19 and 21.
As an additional example, the prior art teaches the following compound on page 15:
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The compound above has the same structure as compound 5C recited in instant claims 19 and 21.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not teach an embodiment where a compound was actually administered to a subject in need thereof and does not explicitly state that the compound is administered to a subject having (according to instant claim 13) “a disease or condition selected from a disorder resulting from telomere or telomerase dysfunction”. Furthermore, Applicant’s elected species is directed to an analogous compound except where prior art compound 45_A or 45_B contains a chloro-substituent.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
At least in the interest of determining which of the disclosed examples would provide optimum treatment results in the utility of the prior art, a person having ordinary skill in the art would have been motivated to test the individual examples of the prior art in the treatment of hepatitis B viral infection. Furthermore, Han et al. teach in paragraph [0003] that chronic hepatitis B leads to chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC) and teach in paragraph [0005]: “It is worth noting that disease progression of cirrhosis and hepatocellular carcinoma is also largely associated with persistent secretion of HBsAg.” Accordingly, a person having ordinary skill in the art in seeking to treat patients having hepatitis B would expect to encounter patients additionally having hepatocellular carcinoma and would expect patients having hepatocellular carcinoma to be in significant need of treating hepatitis B since hepatocellular carcinoma occurs with chronic infection. Regarding the scope of “a disease or condition selected from a disorder resulted from telomere or telomerase dysfunction,” the instant claims do not define the set of conditions; however, Yang et al. teach on page 1 (Background): “Telomere shortening is an important molecular event in hepatocellular carcinoma (HCC) initiation….” Accordingly, at least since telomere shortening is recognized to occur in HCC initiation, the broadest reasonable interpretation of “a disease or condition elected from a disorder resulted from telomere or telomerase dysfunction” is deemed to embrace hepatocellular carcinoma.
Regarding Applicant’s elected species of compound 22C, this compound is a positional isomer of the following compounds disclosed on page 15 of Sun et al.:
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It is well established that position isomers are prima facie structurally obvious even in the absence of a teaching to modify. The isomer is expected to be preparable by the same method and to have generally the same properties. This expectation is then deemed the motivation for preparing the position isomers. See: Ex parte Englehardt, 208 USPQ 343, 349; In re Mehta, 146 USPQ 284, 287; In re Surrey, 138 USPQ 67; Ex Parte Ullyot, 103 USPQ 185; In re Norris, 84 USPQ 459; Ex Parte Naito, 168 USPQ 437, 439; Ex parte Allais, 152 USPQ 66; In re Wilder, 166 USPQ 545, 548; Ex parte Henkel, 130 USPQ 474; Ex parte Biel, 124 USPQ 109; In re Petrzilka, 165 USPQ 327; In re Crownse, 150 USPQ 554; In re Fouche, 169 USPQ 431; Ex parte Ruddy, 121 USPQ 427; In re Wiechert, 152 USPQ 247, In re Shetty, 195 USPQ 753; In re Jones, 74 USPQ 152, 154; and In re Mayne, 41 USPQ2d 1451 (in which the Court took notice of the extreme similarity between the amino acids leucine and isoleucine: “In fact, Leu is an isomer of Ile -- an identical chemical formula with differences only in the chemical bonding of the atoms. The side chains…of Leu and Ile have the same number of hydrogen and carbon atoms…The structure of Leu and Ile alone suggest their functional equivalency” (at 1454-1455)).
For example, “Position isomerism has been used as a tool to obtain new and useful drugs” (Englehardt) and “Position isomerism is a fact of close structural similarity” (Mehta, emphasis in the original). Note also In re Jones, 21 USPQ2d 1942, which states at 1943 “Particular types or categories of structural similarity without more, have, in past cases, given rise to prima facie obviousness”; one of those listed is “adjacent homologues and structural isomers”. Position isomers are the basic form of close “structural isomers.” Similar is In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.” Note also In re Deuel 34 USPQ2d 1210, 1214 which states, “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds … a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para).” See also MPEP 2144.09(II).
Sun et al. particularly teach that substituents on the corresponding thiophene ring can be found at any position in the following generic structure on page 4:
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Furthermore, the prior art teaches particular options for R2 including the following embodiment on page 4:
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The prior art additionally teaches examples having the chloro-substituted thiophene with one of the two options for R2 in the embodiment above as follows on page 15:
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Accordingly, a person having ordinary skill in the art would have been motivated to prepare the instantly claimed positional isomer and to apply them in the utility of the prior art, i.e. treating hepatitis B viral infection including subjects having developed hepatocellular carcinoma.
The instantly claimed structure of compound 22C is disclosed on page 37 of Sun et al. en route to additional embodiments; however, for the reasons discussed above, a person having ordinary skill in the art would have reasonably expected the instantly claimed compound 22C to be a similarly useful member of the prior art genus with utility in treating hepatitis B infection.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW P COUGHLIN whose telephone number is (571)270-1311. The examiner can normally be reached Monday - Friday, 10 am - 6 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at 571-272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626
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