DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 31-59 are currently pending in this Application.
Information Disclosure Statement
Applicant’s Information Disclosure Statements (IDS), filed July 03, 2025 follow the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner, please refer to the signed copies of Applicant’s PTO-1449 forms, attached herewith.
Response to Restriction
Applicants’ election, without traverse, the methods of using products of Formula I,
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and the species,
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in response filed July 01, 2025 is acknowledged. Therefore, the restriction requirement is considered proper and is maintained.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(b) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. Any amendment of inventorship must be accompanied by a petition under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i).
The scope of the invention of the elected subject matter is as follows:
The elected species was found to be free of prior art and therefore, the scope of the examined subject matter was expanded to include other species of products of Formula I,
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,
Claim Rejections — Improper Markush Group
The nonstatutory Markush grouping rejection is based on a judicially approved “improper Markush grouping” doctrine. Claims 31-34 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The claims are drawn to a method of using millions of compounds, having any bicyclic ring core with any X1-X5, Q1, RI-R4, substituted or unsubstituted, each moiety very different structurally from another, are attached. Therefore, it cannot be said that all members of the Markush group have a single structural similarity from which the activity flows. Specifically, the species of the Markush group do not share a “single structural similarity” because there are no required structural features within the compounds of formula I such that each member of the group would have at least one structural feature, which feature is essential to the activity/function of the claimed compounds, in common.
In addition, at least (2) applies since each alternatively usable member of the Markush group does not share a common use. Rather, the specification discloses that the compounds are useful for RESTORING MUTANT p53 FUNCTION: however, there is no common core in the compounds of formula I that are known for RESTORING MUTANT p53 FUNCTION. It is suggested that applicant amend the claims to contain only proper Markush groupings to compounds sharing a single structural similarity and a common use, wherein the common use shared by the compounds is a result of the structural similarity essential to the function of the compounds.
The question of whether the lack of a specific statutory basis is a fatal flaw against a holding of an Improper Markush group was decided in Jn re Harnish, 206 USPQ 300, 305, where the court said, “... we think it should be clear from our actions in Weber and Haas II that we there recognized the possibility of such a thing as an "improper Markush grouping." We were and are aware that it does not have a specific statutory basis ...” The court went on to reverse the rejection, (which had been made by the Board under Rule 196(b)) but not on the lack of a specific statutory basis but rather, “Clearly, they are all coumarin compounds which the board admitted to be "a single structural similarity." We hold, therefore, that the claimed compounds all belong to a subgenus, as defined by appellant, which is not repugnant to scientific classification. Under these circumstances we consider the claimed compounds to be part of a single invention so that there is unity of invention...” Thus, the rejection was overturned not because of any lack of a specific statutory basis, but because of the specific facts in the case. The Markush group was held proper in that case, as was the case also in Ex parte Price 150 USPQ 467, Ex parte Beck and Taylor, 119 USPQ 100, and Ex parte Della Bella and Chiarino 7 USPQ2d 1669. Cases where the Markush group was held improper include Ex Parte Palmer, 7 USPQ 11, In re Winnek, 73 USPQ 225, In re Ruzicka, 66 USPQ 226, Ex parte Hentrich, 57 USPQ 419, Ex parte Barnard, 135 USPQ 109, Ex parte Reid, 105 USPQ 251, Ex parte Sun and Huggins, 85 USPQ 516, In re Thompson and Tanner, 69 USPQ 148, In re Swenson, 56 USPQ 180, and Jn re Kingston, 65 USPQ 371. Note In re Milas 71 USPQ 212 in which the structural difference between vitamin A and D was sufficient to uphold the improper Markush rejection. Also see In re Winnek 73 USPQ 225 and In re Ruzicka 66 USPQ 226 in which structural differences were small and yet a similar holding was maintained. All these cases involved compounds in the pharmaceutical art known to be structure -sensitive. Of particular interest is Ex Parte Hozumi, 3 USPQ2d 1059, which reversed an improper Markush rejection “in view of the relatively large proportion of the structure of the compounds in the claimed class which is common to the entire class.” Here, by contrast, the amount in common is none, relative to the entire molecule.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 31-59 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Patent No. 11,938,124 B2 (
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) in view of U.S. Patent No. 6,603,008, U.S. Patent No. 6,221,335, U.S. PGPub no. 20070082929, U.S. PGPub no. 20070197695, U.S. Patent no. 7,517,990.
The instant elected claims are directed to method of treating cancer using deuterated products of Formula
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.
The primary reference is an example of a reference teaching methods of treating cancer, wherein the cancer expresses a mutant p53 protein, using products of Formula
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The rejected claims differ from the primary reference in that the claimed compound is deuterated. The secondary references teach that such a modification is obvious, for two separate reasons.
First, one is motivated to prepare deuterated versions of drugs to obtain a version with better pharmaceutical properties.
U.S. Patent no. 6,603,008 teaches "[S]ubstitution with heavier isotopes such as deuterium, i.e. 2H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances" (see col. 6, lines 59-67 and col. 7, lines 11-16).
U.S. Patent no. 6,221,335 teaches that “by deuterating drugs, we have likely … increased the lipophilic nature of the molecule” and, via the deuterium isotope effect, produced a derivative “less easily cleaved by metabolic (or destructive) processes. Hence, the elimination half-life of the drug is prolonged and the drug's therapeutic effects are increased.”
U.S. PGPub 20070082929, paragraph 0014 states, “Deuteration of pharmaceuticals to improve pharmacokinetics (PK), pharmacodynamics (PD), and toxicity profiles, has been demonstrated previously with some classes of drugs.
U.S. PGPub 20070197695 states, “Deuteration can yield pharmaceuticals having improved bioavailability and reduced the toxicity.”
U.S. Patent no. 7,517,990 states, “a deuterated compound is very useful in elucidation of reaction mechanism and substance metabolism and used widely as a labeled compound. Said compound is also known to be useful as drugs, pesticides … and the like due to change in stability and property itself by isotope effect thereof.”
Second, and as an alternative branch, one is motivated to prepare deuterated versions of drugs, which can be used to obtain valuable information about how the un-deuterated drug or closely related drugs act in the body. Note the quotation for U.S. Patent no. 7,517,990 above.
U.S. Patent no. 6,440,710 states, “Deuterium- and tritium-labeled organic compounds have become increasingly important for the role they play in structure determination, mechanistic studies, and elucidation of biosynthetic pathways and in biochemical studies.”
Hence, it is clear that under either of these two branches, “a person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and that there would have been a reasonable expectation of success." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 80 USPQ2d 1641, 1645.
Moreover, given that there is always a need to enhance the pharmacological effects of a compound (e.g. increased in vivo half-life) without significantly altering its basic chemical structure (first branch), or that there is always a need to reduce the time, cost, risk, and statistical imprecision of pharmacokinetic studies (e.g. measure bioavailability or identify metabolites) (second branch), and that there is only a limited number of ways that this can be done, it would be obvious to pursue a potential solution that has a reasonable expectation of success. See e.g. KSR International Co. v. Teleflex Inc., 1385, 1397; Pfizer, Inc. v. Apotex, Inc., 82 USPQ2d 1321; Alza Corp. v. Mylan Laboratories, Inc., 80 USPQ2d 1001; In re Kubin, 90 USPQ2d 1417; In re O’Farrell, 7 USPQ2d 1673, 1681; In re Eli Lilly & Co., 14 USPQ2d 1741; In re Ball Corp., 18 USPQ2d 1491.
In addition, it is clear under both branches that deuteration per se is a known improvement technique for getting a more useful version of the pharmaceutical, and that the improvement is of a predictable nature, as is seen by the success reported in the various secondary references. Thus, it would have been obvious to one of ordinary skill in the pharmaceutical art to have applied this known improvement technique in the same way to the compound of the primary reference to obtain the results reasonably predictable from the secondary references. See e.g. KSR International Co. v. Teleflex Inc., 1385, 1396; Ruiz v. AB Chance Co., 69 USPQ2d 1686; In re Nilssen, 7 USPQ2d 1500.
Accordingly the rejected claims are deemed obvious.
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 obviousness-type 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); and 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 §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claims are either anticipated by, or would have been obvious over, the reference claims.
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims are directed to the same art specific subject matter.
Claims 31-59 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 11,963,953 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims substantially overlap the compounds of the reference claims; the compounds are covered by the referenced claims. The difference between the instant and the patented claims is in scope only. The claims are not identical, but there is significant overlap of subject matter.
Both sets of claims are directed to methods of treatin cancer using deuterated products that include the elected species,
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. The indiscriminate selection of “some” among “many” is prima facie obvious, In re Lemin, 141 USPQ 814 (C.C.P.A. 1964).
“Factors that may be considered in determining level of ordinary skill in the art include: (1) the educational level of the inventor; (2) type of problems encountered in the art; (3) prior art solutions to those problems; (4) rapidity with which innovations are made; (5) sophistication of the technology; and (6) the education level of active workers in the field.” Envtl. Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983) (citing Orthopedic Equip. Co. v. All Orthopedic Appliances, Inc., 707 F.3d 1376, 1381-82 (Fed. Cir. 1983)). The above factors are not exhaustive, but are a guide. Id.
In this case, the education level of the inventor and the education level of active workers in the field of organic chemistry, as well as the high degree of sophistication required to solve problems encountered in the art, a person of ordinary skill in the art would likely have at least a college degree in the field of organic chemistry, with industry experience, i.e., a masters or doctorate level of skill and knowledge in the laboratory. Thus, the level of skill in the art is relatively high.
“Structural similarity between claimed and prior art subject matter, proved by combining references or otherwise, where the prior art gives reason or motivation to make the claimed compositions, create a prima facie case of obviousness.” Takeda v. Alphapharm, 83 USPQ2d 1169 (Fed. Cir. 2007) (quoting In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990). “The ‘reason or motivation’ need not be an explicit teaching that the claimed compound will have a particular utility; 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.” Aventis v. Lupin, 84 USPQ2d 1197 (Fed. Cir. 2007) (citing Dillion, 919 F.2d 692). “Once such prima facie case is established, it falls to the applicant or patentee to rebut it, for example with a showing that the claimed compound has unexpected properties.” Id.
MPEP 804 states: “where the claims of an application are not the "same” as those of the first patent, but the grant of a patent with the claims in the application would unjustly extend the rights granted by the first patent, a double patenting rejection under nonstatutory grounds is proper.”
Although the conflicting claims are not identical, the Examiner finds that a person having ordinary skill in the art would recognize that the claimed invention would unjustly extend the rights granted to U.S. Patent No. 8,435,968 B2, because a hypothetical infringer of U.S. Patent No. 8,193,225 B2 would necessarily be an infringer of the claimed invention. Accordingly, U.S. Patent No. 8,435,968 B2 renders the instant claims obvious absent a showing of unpredictability or comparative evidence suggesting otherwise.
Claim Objections
Claims 39-54 are objected for containing non-elected subject matter.
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAMAL A SAEED whose telephone number is (571) 272-0705.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Joseph K. McKane, can be reached at (571) 272-0699.
Communication via Internet e-mail regarding this application, other than those under 35 U.S.C. 132 or which otherwise requires a signature, may be used by applicant and should be addressed to [Symbol font/0x5B]joseph.mckane@uspto.gov[Symbol font/0x5D]. All Internet e-mail communications will be made of record in the application file. PTO employees will not communicate with applicant via Internet e-mail where sensitive data will be exchanged or where there exists a possibility that sensitive data could be identified unless there is of record an express waiver of the confidentiality requirements under 35 U.S.C. 122 by the applicant. See the Interim Internet Usage Policy published by the Patent and Trademark Office Official Gazette on February 25, 1997 at 1195 OG 89.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or public PAIR only. For more information about the pair system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197.
/Kamal A Saeed/
Primary Examiner, Art Unit 1626