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 .
Response to Arguments
Applicant’s response from 9/11/2025 is acknowledged.
Claim Objections
In view of Applicant’s claim amendment this objection is hereby withdrawn.
Claim Rejections - 35 USC § 112(d)
Applicant’s arguments have been found to be persuasive, in view of which this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 112(b)
Applicant’s arguments and claim amendments overcome the rejection, in view of which this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 102
Applicant has argued that the rejections should be withdrawn, despite the CIP later priority date of April 13, 2018, because the examined and elected species of compound was disclosed in Applicant’s chain of priority as early as the priority date of US application No. 14/686,640 filed on April 14, 2015. The Examiner has verified this statement, and agrees with Applicant that the claimed species of compound is indeed disclosed therein.
PNG
media_image1.png
115
863
media_image1.png
Greyscale
(compound 11, Table 1, p. 140).
In accordance, the 102 rejections over the elected species are hereby withdrawn.
However, the claimed genus of compounds is very huge and very diverse, and for which the Markush rejection below is maintained, and for which there is a significant search burden. Further, the instant application has been filed as a CIP, and it cannot be easily identified with such vast subject matter, which compounds have an earlier priority date based on that of the ‘640 application, and which compounds have a later prior date based on the CIP filing date.
The search has now been further expanded to encompass the following species of compound:
PNG
media_image2.png
99
338
media_image2.png
Greyscale
The new species reads on Applicant’s claims 43 and 44.
Claim Rejections - 35 USC § 112(b)- Markush grouping of alternatives
Applicant has made some small claim amendments, and argued that they overcome the rejection as follows:
PNG
media_image3.png
466
701
media_image3.png
Greyscale
PNG
media_image4.png
58
710
media_image4.png
Greyscale
The Examiner first of all notes that Applicant’s amendments are fairly small, and do not essentially address the rejection vis-à-vis the breadth and diversity of the claimed subject matter. In view of Applicant’s claim amendments, a modified rejection has been made below. Moreover, Applicant has not even attempted to address the end of the office action, which provides:
The Markush grouping of claims 40-44, 47 and 48 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons.
[. . .]
Applicant’s specification further does not show that they are functionally equivalent and have a common use.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Indeed, there is no question that the specification does not show that the claimed compounds are functionally equivalent, and have a common use. Quite to the contrary. Depending on subsets/ small genuses, of very diverse structures from one to the next, the claimed compounds are indeed discloses to have uses as diverse as, inter alia: HSP90 inhibitors; kinase and phosphatase inhibitors; HDM2/MDM2 inhibitors; compounds targeting human BET bromodomain-containing proteins; HDAC inhibitors; human lysine methyl transferase inhibitors; angiogenesis inhibitors; immunosuppressive compounds; compounds targeting the aryl hydrocarbon receptor (AHR); compound targeting RAF receptor (kinase); compounds targeting FKBP; compounds targeting androgen receptor (AR); compounds targeting estrogen receptor (ER) ICI-182780; compounds targeting thyroid hormone receptor (TR); compounds targeting HIV protease; compounds targeting HIV integrase; compounds targeting HCV protease; compounds targeting acyl-protein thioesterase-1 and -2 (APT1 and APT2). (Specification, p. 40-64). But the list does not even stop here, and is even far longer than this. See, e.g., the following portions of the specification, which provide:
PNG
media_image5.png
145
713
media_image5.png
Greyscale
PNG
media_image6.png
833
646
media_image6.png
Greyscale
PNG
media_image7.png
316
620
media_image7.png
Greyscale
(p. 97-99).
PNG
media_image8.png
48
630
media_image8.png
Greyscale
PNG
media_image9.png
819
609
media_image9.png
Greyscale
PNG
media_image10.png
821
617
media_image10.png
Greyscale
PNG
media_image11.png
811
614
media_image11.png
Greyscale
PNG
media_image12.png
819
609
media_image12.png
Greyscale
PNG
media_image13.png
49
611
media_image13.png
Greyscale
(p. 101-p. 106).
In view of the foregoing, the rejection is maintained. Claims 40-44, 47 and 48 are pending, and have been examined herewith.
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.
Claim 48 is 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.
Claim 48 is vague and indefinite, because it depends from a cancelled claim- claim 45.
In the interest of compact prosecution, the Examiner interprets claim 48 is dependent on claim 43 instead.
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 40-44, 47 and 48 are rejected on the 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 claims are also rejected under 35 U.S.C. 112(b) as one skilled in the art cannot determine the metes and bounds of the Markush claim due to an inability to envision all of the members of the Markush grouping.
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a "single structural similarity" and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a "single structural similarity" and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claims 40-44, 47 and 48 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons.
Claim 40 recites compounds of the following formula: PTM-L-CLM. PTM is recited to be a single chemistry structure. However, with respect to the remainder of the molecule (-L-CLM), the recited compounds do not share a "single structural similarity".
Here is what L is defined to be in claim 40:
PNG
media_image14.png
437
727
media_image14.png
Greyscale
PNG
media_image15.png
150
697
media_image15.png
Greyscale
As can be seen from this description, the compounds belong to completely different and improper Markush groupings of alternatives. First, the chain length is highly varied (from q being from 1 to 10). Next, A is defined very broadly. It can be just a straight chain, or a double bond, or a triple bond, or can also have various heteroatoms, such as
PNG
media_image16.png
33
165
media_image16.png
Greyscale
PNG
media_image17.png
30
131
media_image17.png
Greyscale
. Then, A can also be various cyclic compounds, e.g. cycloalkyl, heterocyclyl, aryl, heteroaryl. This by itself introduces completely different core structures. Further, all of these substituents can be further substituted, with a very diverse group of substituents, which include various carbon groups, halogens, heteroatoms, and various cyclic compounds, e.g. cycloalkyl, heterocyclyl, aryl, heteroaryl.
Here is what L is defined to be in claim 43:
PNG
media_image18.png
118
714
media_image18.png
Greyscale
As can be seen from claim 43, the compounds belong to completely different and improper Markush groupings of alternatives as well, to include because they disclose compounds with very different core structures, i.e. with heterochains, with other than the (poly)ethylene glycol groups (C2nH4n+2On+1.), but also with various chemical linker substituents, which include aryl, phenyl, benzyl and heterocycle.
Here is what L was defined to be in claim 45, which specifically exemplifies points the Examiner made above. The claim is now cancelled, but the broader independent claims, which define L stand, and thus, the description of the Specification pertaining to this definition of L stands just as well (see, e.g. Specification at [0081]).
PNG
media_image19.png
165
553
media_image19.png
Greyscale
PNG
media_image20.png
667
604
media_image20.png
Greyscale
PNG
media_image21.png
212
576
media_image21.png
Greyscale
Applicant’s claims further define, with reference to claim 40, CLM as follows:
PNG
media_image22.png
196
711
media_image22.png
Greyscale
PNG
media_image23.png
395
670
media_image23.png
Greyscale
Here again, Applicant is claiming multiple core structures. For instance, W can be CH2, but it also can be C=O. Similarly, X or Z can be absent, but they also can be C=O.
In the instant case, for the reasons provided above, a boundary cannot be drawn separating embodiments encompassed by the claim from those that are not, thus further rendering the claims indefinite. See also MPEP § 2173.05(h).
Applicant’s specification further does not show that they are functionally equivalent and have a common use. In fact, the Specification very specifically sets forth that they do not have a common use. (See, cf. Specification at p. 97-106).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 41, 42 and 48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Han et al., Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer, J Med Chem, 2021 Sep 9;64(17):12831-12854. doi: 10.1021/acs.jmedchem.1c00882, Epub 2021 Aug 25 (“Han”).
Han discloses the following proteolysis targeting chimera (PROTAC) small-molecule degrader- ARD-2128. Per Han, “ARD-2128 achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity. This study supports the development of an orally active PROTAC AR degrader for the treatment of prostate cancer and provides insights and guidance into the design of orally active PROTAC degraders.” (Abstract, Graphical Abstract).
PNG
media_image2.png
99
338
media_image2.png
Greyscale
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 SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached on (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SVETLANA M IVANOVA/ Primary Examiner, Art Unit 1627