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 .
Election/Restrictions
Applicant’s election without traverse in the reply filed on 11/14/2025 is acknowledged:
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Compound 9 is the following structure:
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Claims 1-6, 22-24, 29, 32, 33, 35, 37 and 41-45 cover the elected compound and are treated on the merits, below.
Specification
The use of a trade names or marks used in commerce has been noted in this application. See for example TECAN EVO (WALL-E), page 44 of the specification.
The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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 1-6, 22-24, 29, 32, 33, 35, 37 and 41-45 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) contains 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 rejected claims cover compounds comprising an E2 binding moiety, a target protein binding moiety, and a linker (L) which covalently attaches the E2 binding moiety to the target protein binding moiety. The rejected claims also cover compositions and methods of using the compounds.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (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”); In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”).
With regard to the recited genus of compounds, the following applies:
Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “...a generic claim may define the boundaries of a vast genus of chemical compounds...the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
See also Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species.
Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) states that “it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it”.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(i), the court states, "An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention."
Courts have stated that “[i]n claims involving [non-genetic] chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). (emphasis added).
There is no such specificity here, nor could one skilled in the art identify particular compounds encompassed by the rejected claims. Specifically, Applicant desires patent protection for th recited compound comprising and E2 binding moiety, a target protein binding moiety, and a linker which covalently attaches the E2 binding moiety to the target protein binding moiety. However, in view of the above, the specification does not provide adequate written description of the claimed genus of these compounds. Specifically, Applicant fails to disclose any other compounds, besides those covered by the formulas in the specification and claims, and in relation to the above, these disclosed species or subgenre do not represent the substantial variety covered by the genus of compounds.
With regard to the functional definitions of an E2 binding moiety, a target protein binding moiety, and a linker, the specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116) because the specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited compounds. At best, it simply indicates that one should test an inordinate number of compounds to see if the compounds can perform the required functions of an E2 binding moiety, a target protein binding moiety, and linker, see In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”).
The Examiner acknowledges that a working example or exemplified embodiment is not necessarily a requirement for description. However, where a generic claim term is present in a claim, as in the present application, and defined only by functional characteristics, the specification must convey enough information, e.g., via sufficient representative examples, to indicate invention of species sufficient to constitute the genus. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 2 (Fed. Cir. 2002). The written description requirement “requires a description of an invention, not an indication of a result that one might achieve if one made that invention.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent...‘is not a reward for the search, but compensation for its successful conclusion.’ ... For that reason, the written description requirement prohibits a patentee from ‘leaving it to the ... industry to complete an unfinished invention.’” (citations omitted)).
Accordingly, the specification lacks adequate written description for the recited compounds.
Claims 43 and 45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of degrading proteins or treating specific diseases linked to a particular protein, does not reasonably provide enablement for treating a disease responsive to degradation of a target protein in general. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
“The standard for determining whether the specification meets the enablement requirement [in accordance with the statute] was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988). See also United States v. Telectronics, Inc., 857 F.2d 778, 785, 8 USPQ2d 1217, 1223 (Fed. Cir. 1988) ("The test of enablement is whether one reasonably skilled in the art could make or use the invention from the disclosures in the patent coupled with information known in the art without undue experimentation."). A patent need not teach, and preferably omits, what is well known in the art. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991); Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1384, 231 USPQ 81, 94 (Fed. Cir. 1986), cert. denied, 480 U.S. 947 (1987); and Lindemann Maschinenfabrik GMBH v. American Hoist & Derrick Co., 730 F.2d 1452, 1463, 221 USPQ 481, 489 (Fed. Cir. 1984). Determining enablement is a question of law based on underlying factual findings. In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991); Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1576, 224 USPQ 409, 413 (Fed. Cir. 1984).” See M.P.E.P. § 2164.
Here, the nature of the invention is treating diseases known to be linked to a particular protein by treating with PROTAC’s (Proteolytic Targeting Chimeras). In this regard, determining how a particular protein’s activity impacts etiology of disease is not routine and the level of ordinary skill in the art of pharmacology is high, as an ordinary artisan in this art needs specialized knowledge of the complex biochemistry and of a particular disease.
Applicant is reminded of the heightened enablement for these types of inventions: Specifically, the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. [I]n the field of chemistry generally, there may be times when the well-known unpredictability of chemical reactions will alone be enough to create a reasonable doubt as to the accuracy of a particular broad statement put forward as enabling support for a claim. This will especially be the case where the statement is, on its face, contrary to generally accepted scientific principles. Most often, additional factors, such as the teachings in pertinent references, will be available to substantiate any doubts that the asserted scope of objective enablement is in fact commensurate with the scope of protection sought and to support any demands based thereon for proof. [Footnote omitted.].
Therefore, either the state of the art or the specification needs to establish that those of ordinary skill can determine if the underlying cause of a disease’s is defined by a protein.
Here prior art teaches that protein degradation, especially using targeted methods like PROTAC’s, treats diseases by eliminating disease-causing proteins, treating specific disease such as multiple myeloma, solid tumors, Alzheimer's, Parkinson's, Huntington's, ALS, rheumatoid arthritis, lupus, and viral infections, by using a cell's own biochemistry to tag and destroy disease-causing or overactive proteins, such as STAT3, BCL2, WRN, and BRD4.
See:
Podolak, Targeted protein degradation to treat cancer, St. Jude Research, downloaded 17 December 2025 from https://www.stjude.org/research/progress/2023/targeted-protein-degradation-to-treat-cancer.html;
Song et al, Journal of Autoimmunity, Volume 156, 2025, 103475;
Fang et al., J. Med. Chem. 2022, 65, 11454−11477;
Zhao et al., Signal Transduction and Targeted Therapy (2022) 7:113;
Targeted Protein Degradation to Treat Advanced Solid Tumors, 2023, downloaded 17 December 2025 from https://letswinpc.org/research/protein-degradation-advanced-tumors/.
Therefore, the use of PROTAC’s for treatment of specific diseases associated with STAT3, BCL2, WRN, and BRD4 may be characterized as “known”, but use of such compounds to treat prophetic protein-causing diseases is not predictable. For instance, there may not be a nexus between a disease and proteins or the use of PROTAC’s as a treatment. Thus, it is unpredictable whether a disease is caused by a particular overactive protein if there doesn’t appear to be a clear link between the disease and a protein.
The specification fails to remedy the state of the art. Here the specification shows activity of PROTAC’s against BRD4. Therefore, a nexus may be established between in vitro results and the treatment of those diseases associated with that protein. The specification does not provide any additional examples or guidance on how to use the recited compounds against any other diseases. Thus, the specification provides sufficient teachings only for the enablement of treatment of diseases associated with BRD4.
The prior art provides no compensatory guidance and it would require undue experimentation to practice the invention for treatment of diseases covered by the claims not associated with STAT3, BCL2, WRN, and BRD4. The amount of experimentation would be undue because it would require determining which proteins to target for a particular disease. Specifically, as outlined above, it is not routine to determine how to identify a disease’s molecular cause. In the instant case, it is only known that the instant PROTAC’s have degrading activity against specific proteins. This means that significant experimentation would be required to determine if the instant compounds can be effective in diseases not known be associated with an overactive protein. Those of ordinary skill in the art cannot extrapolate between a protein’s activity and a disease’s underlying cause. Moreover, there is little guidance, in both the prior art and the specification, with respect to the use of such compounds to treat diseases other than those known to be associated with disease-causing proteins.
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 43-45 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.
Claim 43 recites a method of treating a disease responsive to degradation of a target protein comprising administering to the subject an effective amount of the instant compounds. The criteria of “responsive to degradation of a target protein” is not defined in the specification or claims. Therefore, those of ordinary skill would not know what diseases are covered by the claim.
The term “the subject” in claim 43 lacks antecedent basis.
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.
Claims 1-6, 22-24, 29, 32, 33 and 42-45 are rejected under 35 U.S.C. 103 as being unpatentable over Applicant’s Background section (Background)., or WO 2013106643 or (WO 643) or Bondeson et al., NATURE CHEMICAL BIOLOGY 2015, vol. 11, 2015, pages 611-617 (Bondeson) in view of:
Winter et al., SCIENCE 2015, vol. 348, no. 6241, pages 1376-1381 (Winter).
Regarding claims 1-3, 42, 43 and 45 Applicant’s Background establishes that proteolysis targeting chimeras (PROTACs) have become an appealing technology for modulating a protein of interest (POD. PROTACs are heterobifunctional small molecules with three chemical elements: a ligand binding to a target, a ligand binding to ubiquitin ligase, and a linker for conjugating these two ligands. Different from the competitive- and occupancy-driven process of traditional inhibitors, PROTACs are catalytic in their mode of action and have the potential to degrade the target pathogenic proteins and regulate the related signaling pathways. PROTAC’s targeting about 30 proteins, many of which are clinically validate drug targets, have been developed with several in clinical trials for the treatment of cancer and other diseases.
Also regarding claims 1-3, 42, 43 and 45, WO 643 teaches PROTAC structure comprising a ligand for an intracellular target, a ligand for an ubiquitin ligase and a linker:
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Target proteins are taught:
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Also, regarding claims 1-3, 42, 43 and 45, Bondeson teaches PROTAC structure of ubiquitin ligase moiety, linker and target protein moiety:
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With regard to claims 1, 4-6, 22-24, 29, 32, 33 and 44, the difference between the instant compounds and those taught by the primary references is that the primary references may fail to explicitly teach a compound with a particular E2 binding moiety and BRD4 binding moiety. However, Winter specifically teaches protein degraders with a E3 ubiquitin ligase binding moiety, linker and BRD4 binding moiety, see Abstract:
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The particular structure of the claimed compounds is taught:
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In this way, those of ordinary skill could have applied an E2 binding moiety and a BRD4 binding moiety in a predictable fashion for the purposes of obtaining the recited compounds. As outlined above, the primary references teach PROTAC’s using a chimeric compound comprising ligands that recognize a ubiquitin ligase and a target protein. Winter is for the proposition that the instant E2 and BRD4 ligands are applicable to these PROTAC’s. Specifically, Winter teaches that the particular known technique using these ligands in PROTAC’s that target E3 and BRD4 was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to those therapies that target E3 and BRD, such as PROTACS taught by the primary references, would have yielded predictable results. Accordingly, using the instant E2 binding moiety and BRD4 binding moiety for the purposes of preparing a PROTAC would have been prima facie obvious.
Claims 35, 37 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Applicant’s Background section (Background)., or WO 2013106643 or (WO 643) or Bondeson et al., NATURE CHEMICAL BIOLOGY 2015, vol. 11, 2015, pages 611-617 (Bondeson) in view of:
Winter et al., SCIENCE 2015, vol. 348, no. 6241, pages 1376-1381 (Winter), in further view of:
Raina et al., Proceedings of the National Academy of Sciences of the United States of America, 113(26), 7124–7129 (Raina).
Claims 35, 37 and 41 cover a target protein binding moiety and linker not explicitly taught by the previously applied references. However, it is for that proposition that the examiner joins Raina.
Specifically, with regard to claims 35, 37 and 41, Raina teaches ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology, see Abstract:
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In particular, Raina teaches the BRD4 ligand-linker structure required by the rejected claims:
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See page 7125.
In this way, those of ordinary skill could have applied the instant BRD4 ligand-linker structure for the purposes of obtaining the recited compounds. As outlined above, the primary references teach PROTAC’s using a chimeric compound comprising the recited ligands that recognize a ubiquitin ligase. Raina is for the proposition that the instant BRD4 ligand-linker structure is applicable to these PROTAC’s. Specifically, Raina teaches that the particular known technique using these structures in PROTAC’s that target E3 and BRD4 was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to those therapies that target E3 and BRD, such as PROTACS taught by the primary and secondary references, would have yielded predictable results. Accordingly, using the instant BRD4 ligand-linker structure for the purposes of preparing a PROTAC would have been prima facie obvious.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-6, 22-24, 29, 32, 33, 35, 37 and 41-45 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-6, 22-24, 29, 32, 33, 35, 37 and 41-45 of copending Application No. 18/993,777. This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Janet Epps-Smith, can be reached at telephone number (571)272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646
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