Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
This application is a CON of 17/719,087 (04/12/2022 ABN),
17/719,087 is a CON of 16/799,556 (02/24/2020 ABN),
16/799,556 is a CON of 15/703,688 (09/13/2017 ABN),
15/703,688 is a CON of 15/013,057 (02/02/2016 US9775829)
15/013,057 is a CON of 14/332,207 (07/15/2014 US9273035)
14/332,207 is a DIV of 13/619,137 (09/14/2012 US8871797),
13/619,137 is a DIV of (10/895,789 07/21/2004 US8754238),
10/895,789 has PRO 60/503,586 (09/16/2003),
10/895,789 has PRO 60/489,572 (07/22/2003).
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2003/062206 (”Teegarden”) in view of Chambers, et al. (Bioorg. Med. Chem. Lett., 2002, 12, 1997-99), Burger (“Isosterism and bioisosterism in drug design.” Prog. Drug Res. 37 (1991), pp. 287 -371), Glennon et al. (J. Med. Chem., 1982, 25(10), 1163-68), Nichols, et al. (J. Med. Chem., 1991,34, 276-81), Yevich, et al. (Curr. Med. Chem., 1997, 4(5), 295-312), Barnett et al. ('QuaSAR' Reasearch Monograph 22, 1978, NIDA, 487 pages), and Holtje (The Practice of Medicinal Chemistry, 2nd ed., 2003, Wermuth (editor), Academic Press, pages 387-403) [All cited and of record in parent application 10/895789].
The claimed invention is to a broad genus of compounds of including the scope of claim 1’s formula (I):
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,
covering in excess of billions of species as a result of the broad scope of variable groups. The utility of the claimed compounds are as 5-HT_2A receptor agonists. Serotonin is also known as 5-HT (5-hydroxytryptamine) and these compounds act on a specific subfamily of receptors for serotonin/5-HT known as 5-HT_2A.
The instant specification discloses structures of numerous compounds and provides associated data in Table 6 (p. 174):
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and in vivo studies of compounds 1 and 26 (p. 175-179). The compounds with experimental data are shown below:
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Determining the scope and contents of the prior art
Teegarden teaches compounds which have utility as agonists of 5-HT_2A (identical utility as the instant application). Teegarden specifically states that the compounds with the following structure "exhibits highly selective 5-HT_2A activity." See below:
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Formula (I) includes where R1 is hydrogen, alkoxy, hydroxyl, halogen (claim 1; p. 36, [0153]) In addition, the prior art also identifies the following compounds (page (p. 91-92, 97-111, [0254]):
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Teegarden teaches on page 97 and 110 that the compounds are “preferred compounds” and useful as a modulator of 5-HT2A. The preferred compounds are also specifically claimed in claim 85 (i.e., compound 153, p. 209, line 167; compound 157 on page 209, line 172). Teegarden also teaches, inter alia, on page 52 that compound 8 shows desirable experimental activity "WT 5-HT_2A LSD IC50" of 11 nM. Teegarden employed a method of “screening of compounds” using experimental assays described on page 30 to arrive at the compounds listed above; this process is also known as structure-activity-analysis or structure-activity-relationship (SAR) (see page 36, line [0152]).
Teegarden Tables 6-13 (p. 52-56, 58, 61-63) describe a series of experimental assay results showing IC50 values on the order of nanomolar through various structural modifications. In particular, Teegarden teaches in Table 10 (p. 58) that compound 1 has an AP-3 IC50 value of 0.0003 mM (0.3 nanomolar). Similarly, Teegarden reports IP3 AP-3 IC50 assay values for compounds 165-182 in the table on page 115 with all being on the order of nanomolar.
Chambers (entitled “Translocation of the 5-alkoxy substituent of 2,5-dialkoxyaryalkylamines to the 6-position: effects on 5-HT_(2A/2C) receptor affinity”) teaches the success of positional isomerism of a methoxy group on a phenyl ring for a 5-HT_2A affecting compound. See page 1997-98. The reference “incorporates the aryl-substitution pattern that is typical of this drug class,” (p. 1998, col. 1) and concludes that the results of the substituent studies suggests that oxygen group (of the methoxy and furan oxygen) interacts favorably with the receptor amino acid site (see p. 1998, col. 1, para. 1; p. 1999, col. 2, para. 2). The structure of the compounds suggesting the Chambers methoxy substituent study are depicted below:
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.
Burger teaches drug design through modifications of the structure of known molecules. Burger generally describes the methodology those of ordinary skill in the art utilize to optimize active drug compounds through techniques such as bioisosterism and SAR. For example, the prior art teaches on pages 348-349 the successful implementation of the general approach of ring position isomerism to generate additional pharmaceuticals. The sulfanilamide compounds (199) and (200) were used as an example of how the substituent position on an aromatic group can be moved and maintain or improve the activity of the compound (page 348). In Burger’s example, a methoxy group was moved from one available ring position to another all while maintaining activity. The rationale for this ability is described as altering the electronic localization in a beneficial way. Thus, by this example, Burger teaches that a methoxy substituent can be moved about a ring and one of ordinary skill in the art would have a reasonable expectation that the resulting compound would have similar properties.
Glennon reports on the successful positional isomerism of a methoxy group on a phenyl ring in a series of compounds affecting the 5-HT receptor. Table II describes the in vivo experimental results for the 5-HT receptor:
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.
Glennon also concludes that the dimethoxy susbstitution “is important for high 5-HT receptor affinity.” Page 1167, col. 1, para. 2.
Nichols presented a study on a series of 5-HT2 antagonists in vivo and in vitro wherein the importance of the phenyl ring methoxy substituent was identified. On page 278, col. 2, the reference teaches that the methoxy substituent has a "specific receptor interaction." In addition, on page 279, col. 1, para. 3, upon analyzing the methoxy ring substituent effects, the reference suggests that there is a “necessity for a particular orientation of the oxygen unshared electrons.” The reference concludes with identifing the ring substitution position as “an important region of the molecule for productive receptor interaction.”
Yevich, studied the selectivity of chemical structure for the various 5-HT receptor subtypes. On page 302, col. 1, the reference identifies that a methoxy substituent on a phenyl ring imparted high affinity for several subtypes and that refinements to the electronic structure of the ring introduced a degree of selectivity among the receptor subtypes.
Barnett is a detailed review of structure-activity relationship (SAR) studies including specific studies of compounds binding to the 5-HT receptor. See pages 16-25, pages 159-179, Tables 1-8. Many of the SAR studies of 5-HT receptor agonists specifically analyze the methoxy ring position isomer as shown in table 1 (page 163) below:
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See also Table 8, page 178. The review demonstrates the success of applying SAR and methoxy positional isomerism for 5-HT receptor affecting compounds.
Holtje, is a review of the process used by those of ordinary skill in the art for mapping the binding site of a receptor. On page 394, Holtje presents a case study of the 5-HT_2A receptor. Holtje describes important structural elements for 5-HT_2A receptor binding and presents a map for a particular class of binding compounds. See page 394-95.
Ascertaining the differences between the prior art and the claims at issue
Although Teegarden teaches compound 149 (
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), the compound differs from the instant claims by the position of the methoxy group on the phenyl ring (arrow indicated above).
Resolving the level of ordinary skill in the pertinent art.
One of ordinary skill in the art of pharmaceutical development would be well versed in methods of generating lead compounds via SAR as was done in the cited prior art, for example on page 36 of Teegarden. One of ordinary skill in the art would consider routine and well within their technical grasp the process of altering the position of substituents on drug molecules and screen them for activity on a large scale to improve potency.
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. This circumstance has arisen many times. 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, second paragraph.
Finding of prima facie obviousness.
Upon reading the teachings of Teegarden in view of the prior art cited, one of ordinary skill in the art would immediately recognize potential to improve the potency of the compounds taught therein and by Burger through altering the substituents via positional isomerism. In particular, as identified by Chambers, Glennon, Nichols, Yevich, Barnett and Holtje one of ordinary skill would be overwhelmingly taught that the methoxy group on the aryl ring is important in interactions with the 5-HT receptor. Chambers and Glennon specifically performed the positional isomerism with success. Nichols determined that there were specific interactions between the receptor and the methoxy ring group. Yevich and Barnett showed that methoxy ring position isomers are commonly used in the context of 5-HT receptors. Holtje presented a map of the 5-HT_2A receptor site that suggested sites for modifying binding compounds.
Teegarden specifically discusses the application of SAR to selective 5-HT_2A compounds. Glennon, Nichols, Yevich and Barnett each discuss the successful application of ring position isomerism in the context of 5-HT. This methodology is reasonably applicable to the compound of Teegarden. In addition, the Teegarden compound is an isomer of the instant claims, only differing by position of a group, thus one of ordinary skill in the art would expect the physical properties of the two compounds to be similar.
In Eisai Co. Ltd. v. Dr. Reddy's Laboratories Ltd., 87 USPQ2d 1452, 1454 (Fed. Cir. 2008), the Federal Circuit clarified the proof of obviousness in structural similarity situations such as the present case:
Where, as here, the patent at issue claims a chemical compound, the analysis of the third Graham factor (the differences between the claimed invention and the prior art) often turns on the structural similarities and differences between the claimed compound and the prior art compounds. See Eli Lilly & Co. v. Zenith Goldline Pharms., Inc., 471 F.3d 1369, 1377 [81 USPQ2d 1324] (Fed. Cir. 2006) (noting that, for a chemical compound, a prima facie case of obviousness requires “structural similarity between claimed and prior art subject matter … where the prior art gives reason or motivation to make the claimed compositions” (quoting In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990) (en banc))). Obviousness based on structural similarity thus can be proved by identification of some motivation that would have led one of ordinary skill in the art to select and then modify a known compound (i.e. a lead compound) in a particular way to achieve the claimed compound. See Takeda Chem. Indus. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1356 [83 USPQ2d 1169] (Fed. Cir. 2007). In keeping with the flexible nature of the obviousness inquiry, KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1739 [82 USPQ2d 1385] (2007), the requisite motivation can come from any number of sources and need not necessarily be explicit in the art. See Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499 F.3d 1293, 1301 [84 USPQ2d 1198] (Fed. Cir. 2007). Rather “it is sufficient to show that the claimed and prior art compounds possess a ‘sufficiently close relationship … to create an expectation,’ in light of the totality of the prior art, that the new compound will have ‘similar properties’ to the old.” Id. (quoting Dillon, 919 F.2d at 692).
Eisai Co. Ltd. v. Dr. Reddy's Laboratories Ltd., 87 USPQ2d 1452, 1454 (Fed. Cir. 2008) (emphasis added). Thus, a new compound is found prima facie obvious when there is a close structural similarity and "some reason" to modify the prior art in a particular manner to arrive at the new compound.
This is further supported by the MPEP in section 2144.09(II):
Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977); see also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978).
Therefore, because Teegarden teaches isomers of the instantly claimed compounds and the MPEP states that isomers are presumed to possess similar properties, it would have been obvious to one of ordinary skill in the art to modify the ring position of the methoxy of compound 149 and arrive at the instant invention. The secondary references provide substantial motivation to make such a change to the prior art compound. One of ordinary skill in the art would have been guided by the prior art to make the invention as claimed because Teegarden teaches isomers of the compound, while the secondary references teach how to modify the compound to arrive at the instant invention.
One of ordinary skill in the art would select Compound 149 because it is specifically claimed by Teegarden in claim 85 and it is listed as a “preferred compound” (on page 97 and 110). Furthermore, Teegarden eludes to additional positive experimental data on page 31. Specifically, in Example 7, 120 compounds evidenced at least 50% inhibition in the assay ([0140]). At [0144] Teegarden explains how HTS was applied to 72 compound in parallel. Thus, one of ordinary skill in the art would select Compound 149 for further development in the parallel drug development process that is now commonplace as it was at the time of the Teegarden prior art (see page 36, line [0152]).
Teegarden discusses the process of drug development on page 36, including the generation of directed library compounds in a manner commonly used by those of ordinary skill in the art and discussed in Chambers, Glennon, Nichols, Yevich, Barnett, and Holtje. In addition, Chambers, Glennon, Nichols, and Barnett each provided an example of such a process for drug development wherein a methoxy positional isomer on an aryl ring was successful. Furthermore, Chambers, Nichols, and Yevich each identify the importance of the methoxy group in the context of 5-HT2. Thus, such modifications are commonly performed by those of ordinary skill in the art and are within their knowledge and ordinary creativity.
Alternatively, one of ordinary skill in the art would select Teegarden’s Compound 8 because it showed promise as a lead candidate in the experimental assay. Based on the overwhelming prior art suggesting a methoxy substitution on the aryl group, one of ordinary skill in the art would perform methoxy ring substitutions at the relevant sites identified by the prior art (such as by Holjte). Because of the indications by the prior art that a methoxy substituent was important for receptor interactions, one of ordinary skill in the art would have had a reasonable expectation of success. Similarly, one of ordinary skill in the art would have considered positional isomers on the pyrazole ring including such that R2 would be hydrogen while R3/R4 would be Br/Me.
One of ordinary skill in the art would have been guided by the prior art to make the invention as claimed because Teegarden teaches the homologous compound, while the cited prior art teaches how to modify the compound to arrive at the instant invention. Therefore, the claims are prima facie obvious.
Considering objective evidence present in the application indicating obviousness
Applicant has previously presented two declarations alleged to show secondary considerations. The first is of Bradley Teegarden, filed on 10/3/2008. The Teegarden declaration presents in vitro experimental results comparing the EC50 values for Teegarden’s Compound 158 (
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) in an "inositol phosphate accumulation assay described on page 35 (Example 9D) of WO 2003/062206.” The results are as follows:
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The declaration also presents “in vivo DOI-induced hypolocomotion attenuation activities at 50 mg/kg P.O. in rats” as described “on page 174 (Example 10) of WO 2005/012254.” The results are 47.83 ± 3.0 for compound 158 and 74.33 ± 4.78 for the elected species. The declaration then concludes that the elected species and compound 158 “differ significantly in their activities" according to the presented data “which was a result that was not expected based on the structural similarity of the compounds.”
The second declaration is of Carleton Sage, filed on 9/22/2009. The Sage declaration concludes that the experimental results comparing the EC50 values for Teegarden’s Compound 158 with the elected species in an in vitro "inositol phosphate accumulation assay described on page 35 (Example 9D) of WO 2003/062206” are “statistically different.”
The data presented in the declarations allege that the in vitro and in vivo activity of the elected species was unexpectedly more active than Compound 158.
The Examiner notes that the instant Specification also reports the following data for the same assay in Table 6 (p. 174):
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MPEP § 2144.09 instructs:
A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compounds possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (Affidavit evidence which showed that claimed triethylated compounds possessed anti-inflammatory activity whereas prior art trimethylated compounds did not was sufficient to overcome obviousness rejection based on the homologous relationship between the prior art and claimed compounds.); In re Wiechert, 370 F.2d 927, 152 USPQ 247 (CCPA 1967) (a 7-fold improvement of activity over the prior art held sufficient to rebut prima facie obviousness based on close structural similarity).
However, a claimed compound may be obvious because it was suggested by, or structurally similar to, a prior art compound even though a particular benefit of the claimed compound asserted by patentee is not expressly disclosed in the prior art. It is the differences in fact in their respective properties which are determinative of nonobviousness. If the prior art compound does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, applicant's recognition of the benefit is not in itself sufficient to distinguish the claimed compound from the prior art. In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991).
MPEP § 2145 reminds that the presence of secondary considerations does not control the obviousness conclusion:
Evidence pertaining to secondary considerations must be taken into account whenever present; however, it does not necessarily control the obviousness conclusion. See, e.g., Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1372, 82 USPQ2d 1321, 1339 (Fed. Cir. 2007) ("the record establish [ed] such a strong case of obviousness" that allegedly unexpectedly superior results were ultimately insufficient to overcome obviousness conclusion); Leapfrog Enterprises Inc. v. Fisher-Price Inc., 485 F.3d 1157, 1162, 82 USPQ2d 1687, 1692 (Fed. Cir. 2007)("given the strength of the prima facie obviousness showing, the evidence on secondary considerations was inadequate to overcome a final conclusion" of obviousness); and Newell Cos., Inc. v. Kenney Mfg. Co., 864 F.2d 757, 768, 9 USPQ2d 1417, 1426 (Fed. Cir. 1988). Office personnel should not evaluate rebuttal evidence for its "knockdown" value against the prima facie case, Piasecki, 745 F.2d at 1473, 223 USPQ at 788, or summarily dismiss it as not compelling or insufficient. If the evidence is deemed insufficient to rebut the prima facie case of obviousness, Office personnel should specifically set forth the facts and reasoning that justify this conclusion. See MPEP § 716 - § 716.10 for a additional information pertaining to the evaluation of rebuttal evidence submitted under 37 CFR 1.132.
MPEP § 2145 (emphasis added).
Regarding the in vitro data, based on the disclosure of the prior art one of ordinary skill in the art would expect that in vitro studies of the types of compounds claimed in this application to show inositol phosphate accumulation (the one used in the Teegarden declaration of 10/3/08) IC50 values on the order of nanomolar. For example, on page 58 of the Teegarden prior art, compound 1 showed an IC50 value of 0.3 nanomolar (0.0003 M) in this assay, which is less than that claimed for the elected species value of 0.7 nM. In addition, compound 8 showed an IC50 value of 3.2 nM in the same assay (see page 52). Therefore, while the values observed for the single elected species compound shown above may be considered unexpected (see Board decision dated 10/28/2013 in 10/895789), the expected result is on the order of nanomolar in the assay for structurally similar compounds – i.e. modified compound 149. Thus, the demonstration of the alleged unexpected result is not commensurate in scope with the broad scope of the claims. In re Greenfield, 571 F.2d 1185, 1189, 197 USPQ 227, 230 (CCPA 1978) (evidence of superior properties in one species insufficient to establish the nonobviousness of a subgenus containing hundreds of compounds); In re Lindner, 457 F.2d 506, 508, 173 USPQ 356, 358 (CCPA 1972) (one test not sufficient where there was no adequate basis for concluding the other claimed compounds would behave the same way). In this case based on the evidence of record including Teegarden Tables 6-13 (p. 52-56, 58, 61-63), one of skill in the art would expect nanomolar IC50 values to apply to the full scope of the instant claims which is confirmed by the assay results in instant Table 6 (p. 174).
Regarding the in vivo data presented, it is not clear how this is an unexpected result. For example, a related experimental measurement examining 5-HT2 is that of Sorenson et al. (J Pharmacol Exp Ther August 1993 266:684-691). Sorenson indicates that the results of measurements of 5-HT2 are highly dosage dependent (page 689, col. 1, para. 3). Applicants make measurements at an unusually high dosage of 50 mg/kg. In contrast, the Teegarden prior art made this measurement in doses of 0.1 - 10.0 mg/kg. In addition, the test in WO 2005/012254 (which is the same family as the instant application) provides dosage guidance of “DOI (0.3 mg/kg salt),” (page 175, line 15) which is significantly greater than that used in the declaration. Nevertheless, both the Sorenson and the ‘254 experiments are designed to be tests of drug effects on 5-HT. Another reference, Halberstadt et al. (Neuropsychopharmacology (2009) 34, 1958–1967), describes experiments that show that DOI dosages at greater than 10 mg/kg in this type of experiment are do not measure 5-HT2A effects, but are for a different receptor subtype (page 1964, col. 1, para. 1; page 1965, col. 1, para. 2-3). Halberstadt also questions on page 1965, col. 1, para. 3, the reliability of “high doses of DOI (≥ 10.0 mg/kg)” in affecting locomotor activity.
MPEP § 716.02(b) states that applicant bears the burden of explaining how the data is significant and of practical significance. See MPEP § 716.02(b); “[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness.” Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992); The evidence relied upon should establish “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.” Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992).
Applicant has presented the data in the declaration and argued that “attenuation of DOI-induced hypolocomotion . . . is a test of a property of the compounds – the ability of the compounds to inversely agonize the 5-HT_2A receptor in vivo (see specification, page 174, lines 19-22).” The examiner has reviewed the data, the statement and the cited pages of the specification and requests an explanation of how this is an unexpected result of statistical and practical significance. Based on the Sorenson article one of skill in the art would expect significant dose dependent utility of the compounds. Thus, Applicant’s measurement at the high dose of 50 mg/kg does not clearly establish the practical significance of the result when one of skill in the art would expect the result to be highly dose dependent and this is outside of what would be expected to be the practical dosage used by the prior art Sorenson and Teegarden.
MPEP § 716.02(c) requires the examiner to weigh the evidence of secondary considerations against that supporting obviousness. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (“Evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention.”). Furthermore, the MPEP states that the significance of the alleged unexpected properties is also important:
Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) (Claims were directed to a display/memory device which was prima facie obvious over the prior art. The court found that a higher memory margin and lower operating voltage would have been expected properties of the claimed device, and that a higher memory margin appears to be the most significant improvement for a memory device. Although applicant presented evidence of unexpected properties with regard to lower peak discharge current and higher luminous efficiency, these properties were not shown to have a significance equal to or greater than that of the expected higher memory margin and lower operating voltage. The court held the evidence of nonobviousness was not sufficient to rebut the evidence of obviousness.); In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (Evidence of improved feed efficiency in steers was not sufficient to rebut prima facie case of obviousness based on prior art which specifically taught the use of compound X537A to enhance weight gain in animals because the evidence did not show that a significant aspect of the claimed invention would have been unexpected.).
MPEP § 716.02(c) (emphasis added). As described above, it is not clear how DOI-induced hypolocomotion at an unusually high dosage has practical significance over the expected properties as taught by the prior art. Thus, Applicant has not met their burden as per MPEP § 716.02(b).
In this case, the in vitro and in vivo data has not outweighed the strong evidence favoring obviousness, in part, due to the lack of clarity with respect to how the data represents an unexpected result and the use of dosage levels which do not establish a practical significance.
Therefore, the objective evidence does not outweigh the prima facie case of obviousness and the claims are rejected.
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 8754238. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims compositions including the following species
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, which anticiaptes the instant claims. In addition, the specification includes species supporting the genus of patent claim 1 such as Compound 115 which is the same as the instant elected species and anticipates claims 1-20.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-58 of U.S. Patent No. 9034911. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims compositions including the following species
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, which anticiaptes the instant claims.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 9801856. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims compositions including the following species
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, which anticiaptes the instant claims.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10117851. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims compositions including the following species
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, which anticiaptes the instant claims.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 10583122. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims compositions including the following species
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, which anticiaptes the instant claims.
Conclusion
The claims are not in condition for allowance.
The closest prior art of is that of WO 03/062206 which teaches Compound 158 as depicted on page 160:
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and described as a “preferred compound” “useful as inverse agonists for 5-HT2A receptors” (p. 96, [0252]; p. 97, [0254], p. 110) which the PTAB determined did not render claims such as those in the present application obvious (See US Application 10/895789, decision dated 10/28/2013).
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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, Joseph McKane can be reached at 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626