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
Applicants’ election of Group 2 in the reply filed on 06/19/2026 is acknowledged. Applicants are further correct in that the restriction requirement was missing Claim 82. This was an inadvertent oversight. Claim 82 was dependent from the method of Claim 81 and is henceforth grouped with Group 7. Because applicants did not distinctly and specifically point out any supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
All prior claims were cancelled.
Claims 83-102 have been added and read on the elected invention (Group 2) and thus are pending and under consideration.
Information Disclosure Statement
All three IDSs were considered and are attached. It is noted that Foreign Reference 1 of the IDS submitted 04/07/2025 was not considered because no copy appeared to have been submitted.
Drawings
Figure 6, page 29 is objected to for recitation of the Glycine Linker Coding Sequence (GGAGGCGGT) in the absence of a sequence identifier. See 37 CFR 1.821(c). 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825.
Paragraph 0013 of the specification states that some of the drawings submitted herein may be better understood in color. While the examiner is not objecting to the clarity of the drawings, applicants are reminded that any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Applicants are further reminded that color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 83 is objected to because of the following informalities:
The claim appears to be missing a word after “constitutively active STAT5a (caSTAT5a)” such as protein or transcription factor.
Appropriate correction is requested.
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.
Claims 83-85, and 90-102 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 83 (and dependents identified in para. 8 above) are rejected as indefinite for reciting “a constitutively active STAT5a (caSTAT5a)” as it is unclear what amino acid sequence encompasses a STAT5a protein that is “constitutively active” and what amino acid sequence is represented by the parenthetical expression of “caSTAT5a”. Items within a parenthetical expression render the claim(s) indefinite because it is unclear whether the limitations within the expressions are merely exemplary (similar to “such as” language) or are part of the claimed invention. See MPEP § 2173.05(d). Further, the specification does not provide a limiting definition of what is included or excluded by a constitutively active STAT5a protein. For example, the specification teaches [0032] that constitutively active STAT proteins (ca-STATs), means that the STAT is continuously expressed, independent of the presence of endogenous regulators. This is not a clear or limiting definition. For example, a potential infringer may be using a recombinant STAT5a protein or portion thereof that is expressed and not know whether it was “constitutively active”. This rejection can be obviated by specifically reciting the sequence identifiers that applicants intend to be denoted as caSTAT5a proteins.
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.
Claims 83-85, and 90-102 are also 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. This is a written description rejection.
Claim 83 and rejected dependents thereto are broadly drawn to a fusion protein comprising a “constitutively active STAT5a (caSTAT5a) and a hsp90binding domain. As set forth above, the specification fails to specifically define what is included or excluded by such constitutively active STAT5a proteins. For example, the specification teaches [0032] that constitutively active STAT proteins (ca-STATs), means that the STAT is continuously expressed, independent of the presence of endogenous regulators. The specification further states [0233 and Figure 3] that plasmid DNA of STAT5aER(T2) variants were transfected into cells but it’s unclear what the structure or encoded product of the STAT5aER(T2) variants represents. Thus, the claims are broadly drawn to a genus of proteins referred to only by name (constitutively active STAT5a) with the function of being expressed.
A description of a genus of may be achieved by means of a recitation of a representative number of species, defined by structure, falling within the scope of the genus. However, the instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of “constitutively active” STAT5a proteins that would distinguish the claimed proteins from other molecules that do not have the claimed biological properties. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, the disclosure of such STAT5a proteins is insufficient to describe the large genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe and enable the genus as broadly claimed.
Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991) clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) 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). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of constitutively active STAT5a proteins, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required.
The state of the art of constitutively active STAT5a proteins appears to indicate that these are certain STAT5a proteins (transcription factors) with defined mutations. For example, Grebien et al. (Blood;2008 Jan 31;111(9)) teaches (page 2) that a central pathway in EpoR signaling is the activation of the transcription factor known as signal transducer and activator of transcription 5 (Stat5). Upon phosphorylation, Stat5 dimers translocate to the nucleus, bind to cognate elements in various promoters, and activate transcription. To test whether or not Stat5 was an essential downstream target in erythropoiesis (page 10), they expressed “cS5”- a persistently activated Stat5a mutant. In particular, the cS5 mutant of mouse Stat5a was used which has a serine at position 710 instead of 711 (page 3). As evidenced by Moriggl et al., cS5 is a constitutively active mutant of mouse Stat5a. (See abstract, introduction 3rd para.). Also, Ariyoshi et al. (Jnl.Biol.Chem., Vol. 275, Issue 32, August 2000) previously identified a constitutively active STAT5A mutant (STAT5A1*6) by polymerase chain reaction (PCR)-driven random mutagenesis followed by retrovirus-mediated expression screening. STAT5A1*6 harbors two point mutations, one in the transactivation domain (S710F) and the other in the DNA-binding domain (H298R). In the present paper, they identified and characterized another constitutively active mutant, STAT5A-N642H, which harbors a point mutation on or very close to the phosphotyrosine-binding site in the SH2 domain and has the identical phenotype to that of STAT5A1*6.
Thus, the written description is not commensurate in scope with the claims drawn to a genus of constitutively active STAT5A proteins. In particular, the genus of the world of any constitutively active STAT5A would be very large and highly diverse as the state of the art indicates that these are very defined mutants of wildtype STAT5a proteins. The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., . An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
At present, the disclosure fails to describe the common attributes or characteristics that identify members of the genus. Thus, because the genus is highly variant, the contemplation of a world of “constitutively active STAT5A” proteins is insufficient to describe the genus and one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
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.
Claim(s) 83-84, 86, 88, 90-92, 99-100 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Grebien et al. (Blood;2008 Jan 31;111(9):4511–4522) as evidenced by Moriggl et al. (Cancer Cell, Vol. 7, Issue 1, 2005), and Littlewood et al. (Nucleic Acids Res. 1995;23:1686–1690).
As to claims 83, and 91-92, Grebien et al. teaches a fusion protein comprising a constitutively active STAT5a fused to an hsp90 binding domain wherein the hsp90 binding domain comprises a hormone binding domain and/or wherein the hsp90 binding domain comprises an engineered estrogen receptor binding domain. Under the methods section, Grebien teaches- “For the generation of Stat5-ER* constructs, a point-mutated ligand binding domain of the estrogen receptor (engineered) was fused in frame to the C terminus of Stat5a, or cS5 or Stat5aΔ749, after digestion with SacII. (As evidenced by Moriggl et al., cS5 is a constitutively active mutant of mouse Stat5a. See abstract, introduction 3rd para). See Figure 4A of Grebien et al:
PNG
media_image1.png
126
392
media_image1.png
Greyscale
According to the specification [0009], the hsp90 binding domain can be an estrogen receptor binding domain.
As to claim 84, wherein the caSTAT5a initiates gene transcription of NDRG1, DNAJC6, ST3GAL1, SAMD4A, SSH2, or MAP3K5, such gene transcription would naturally occur as the product of the prior art is identical to the claimed fusion protein.
As to claims 86 and 88, wherein the caSTAT5a comprises a sequence having at least 95% sequence identity to SEQ ID NO:138 (or is encoded by a sequence having at least 95% identity to SEQ ID NO:140); the sequence alignment of murine cS5 was compared to applicant’s SEQ ID NO:138 revealing a 96.6% homology.
Qy=SEQ ID NO:138
Db= murine cS5
RESULT 1
AASEQ2_08192026_121448
Query Match 96.6%; Score 4002.5; DB 1; Length 793;
Best Local Similarity 96.2%;
Matches 764; Conservative 14; Mismatches 15; Indels 1; Gaps 1;
Qy 1 MAGWIQAQQLQGDALRQMQVLYGQHFPIEVRHYLAQWIESQPWDAIDLDNPQDRAQATQL 60
|||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||
Db 1 MAGWIQAQQLQGDALRQMQVLYGQHFPIEVRHYLAQWIESQPWDAIDLDNPQDRGQATQL 60
Qy 61 LEGLVQELQKKAEHQVGEDGFLLKIKLGHYATQLQKTYDRCPLELVRCIRHILYNEQRLV 120
||||||||||||||||||||||||||||||||||| ||||||:|||||||||||||||||
Db 61 LEGLVQELQKKAEHQVGEDGFLLKIKLGHYATQLQNTYDRCPMELVRCIRHILYNEQRLV 120
Qy 121 REANNCSSPAGILVDAMSQKHLQINQTFEELRLVTQDTENELKKLQQTQEYFIIQYQESL 180
|||||||||||:|||||||||||||| ||||||:||||||||||||||||||||||||||
Db 121 REANNCSSPAGVLVDAMSQKHLQINQRFEELRLITQDTENELKKLQQTQEYFIIQYQESL 180
Qy 181 RIQAQFAQLAQLSPQERLSRETALQQKQVSLEAWLQREAQTLQQYRVELAEKHQKTLQLL 240
||||||||| ||:||||:|||||||||||||| |||||||||||||||||||||||||||
Db 181 RIQAQFAQLGQLNPQERMSRETALQQKQVSLETWLQREAQTLQQYRVELAEKHQKTLQLL 240
Qy 241 RKQQTIILDDELIQWKRRQQLAGNGGPPEGSLDVLQSWCEKLAEIIWQNRQQIRRAERLC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ||
Db 241 RKQQTIILDDELIQWKRRQQLAGNGGPPEGSLDVLQSWCEKLAEIIWQNRQQIRRAEHLC 300
Qy 301 QQLPIPGPVEEMLAEVNATITDIISALVTSTFIIEKQPPQVLKTQTKFAATVRLLVGGKL 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QQLPIPGPVEEMLAEVNATITDIISALVTSTFIIEKQPPQVLKTQTKFAATVRLLVGGKL 360
Qy 361 NVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMS 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMS 420
Qy 421 LKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPVVVIVHGSQDHNATA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPVVVIVHGSQDHNATA 480
Qy 481 TVLWDNAFAEPGRVPFAVPDKVLWPQLCEALNMKFKAEVQSNRGLTKENLVFLAQKLFNN 540
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TVLWDNAFAEPGRVPFAVPDKVLWPQLCEALNMKFKAEVQSNRGLTKENLVFLAQKLFNI 540
Qy 541 SSSHLEDYSGLSVSWSQFNRENLPGWNYTFWQWFDGVMEVLKKHHKPHWNDGAILGFVNK 600
||:|||||: :|||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SSNHLEDYNSMSVSWSQFNRENLPGWNYTFWQWFDGVMEVLKKHHKPHWNDGAILGFVNK 600
Qy 601 QQAHDLLINKPDGTFLLRFSDSEIGGITIAWKFDSPERNLWNLKPFTTRDFSIRSLADRL 660
||||||||||||||||||||||||||||||||||||:|||||||||||||||||||||||
Db 601 QQAHDLLINKPDGTFLLRFSDSEIGGITIAWKFDSPDRNLWNLKPFTTRDFSIRSLADRL 660
Qy 661 GDLSYLIYVFPDRPKDEVFSKYYTPVLAKAVDGYVKPQIKQVVPEFVNAFADAGGSSATY 720
|||:|||||||||||||||:|||||||||||||||||||||||||||||| || |:||||
Db 661 GDLNYLIYVFPDRPKDEVFAKYYTPVLAKAVDGYVKPQIKQVVPEFVNAFTDA-GASATY 719
Qy 721 MDQAPSPAVCPQAPYNMYPQNPDHVLDQDGEFDLDETMDVARHVEELLRRPMDSLDSRLS 780
||||||| |||| ||||| ||| ||||||||||||:|||||||||||||||||||:|||
Db 720 MDQAPSPVVCPQPHYNMYPPNPDPVLDQDGEFDLDESMDVARHVEELLRRPMDSLDARLS 779
Qy 781 PPAGLFTSARGSLS 794
|||||||||| |||
Db 780 PPAGLFTSARSSLS 793
Regarding Claim 90, and 99-100, Grebien et al. teach an engineered binding domain of the estrogen receptor that has a point mutation. Grebien et al. reference the structure of this ER binding domain to reference 33 or Littlewood et al. Littlewood et al, teach (1686, 2nd column, last para.) that murine oestrogen receptor (amino acids 281-599) with a G525R mutation was used. This mutant no longer binds E2 (estradiol- biologically active form of estrogen) but still remains responsive to activation by 4-hydroxytamoxifen (4-OHT). Thus, it appears that Grebien used the ER binding domain of Littlewood et al. and this binding domain would inherently bind hsp90 with a lower affinity than it binds a drug molecule because of the G525R mutation that can no longer permits binding to E2. This is similar to the teachings of the specification [0009] where “EBD can be derived from the natural estrogen receptor but include at least one mutation such that the EBD no longer binds estrogen but instead binds a drug molecule with a higher affinity than hsp90.”
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 83-84, 91-92, and 101 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jensen et al. (US20230242936, effectively filed 05/14/2020, currently allowed but not issued).
The applied reference has a common joint inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Jensen et al. teach [0017] a fusion protein comprising a constitutively activated STAT5a and an estrogen receptor connected by a linker (see Figure 9). Since the linker of Claim 101 is not defined and because the specification teaches does not specifically define a linker [0063] the spacers and linkers of the prior art anticipate the claimed linker. As to claim 84, wherein the caSTAT5a initiates gene transcription of NDRG1, DNAJC6, ST3GAL1, SAMD4A, SSH2, or MAP3K5, such gene transcription would naturally occur as the product of the prior art is identical to the claimed fusion protein.
Allowable Subject Matter
Claims 87 and 89 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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, Julie Wu can be reached at 571-272-5205. 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.
/GARY B NICKOL/Primary Examiner, Art Unit 1643
Prosecution Insights