DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Preliminary Amendment filed on May 11, 2023, has been received and entered.
3. Applicant’s election without traverse of Group II (claims 12-14 and 105-106 with SEQ ID NO:53) on November 24, 2025, is acknowledged.
Claim Disposition
4. Claims 4-5, 15-30 and 33-102 have been cancelled. Claims 104-112 have been added. Claims 1-3, 6, 12-14, 31-32 and 103-112 are pending. Claims 12-14 and 105-106 are under examination. Claims 1-3, 6, 31-32, 103-104 and 107-112 are withdrawn from consideration as directed to a non-elected invention.
Information Disclosure Statement
5. The Information Disclosure Statements filed on March 17, 2025 and November 24, 2025 have been considered. A copy of the PTO-1449 form is attached. Note that some references have been lined through because it does not have proper citation of the date.
Drawing
6. The drawings filed on May 11, 2023, have been accepted by the examiner.
Specification Objection
7. The specification is objected to for the following informalities:
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following is suggested: "Recombinant polypeptide and methods for controlled protein degradation in neurodegenerative disease".
The specification is objected to because the sequence notation is improper, see “SEQ ID NOs.:3”, which should be “SEQ ID NO:3” (see page 16).
Appropriate correction is required.
Claim objection
8. Claims 12-14 and 105-106 are objected to for the following informalities:
Claim 12 is objected to for depending from a non-elected claim.
For clarity it is suggested that claim 12 is amended to recite “programmable proteasome targeting (PEST) human domain with spelled out meaning. The dependent claims hereto are also included.
For clarity and precision of claim language it is suggested that claim 105 is amended to read, “An isolated polypeptide…”.
Claim 105 is objected to for the recitation of non-elected subject matter.
For clarity and consistency it is suggested that claim 106 is amended to recite “of” and delete “according to”.
Appropriate correction is required.
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.
9. Claims 12-14 and 105-106 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), 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 claimed invention is directed to “a recombinant polypeptide comprising an antigen-binding domain that binds a protein and the programmable proteaseome-targeting human PEST domain. The claimed invention encompasses a large variable genus of proteins that are not defined by structure or function. In addition, the specification and claims do not adequately describe what is intended or meant by ‘programmable’ (that it is an engineered protein degradation system (proteins with short intracellular half-life that are engineered/programmed degraders) that utilizes a specific amino acid rich sequence (Proline (P), Glutamic acid (E), Serine (S) and Threonine (T), to flag proteins for degradation by the ubiquitin proteasome system (UPS). It is noted that claim 13 recites that the recombinant polypeptide is an intrabody, however, claim 12 is not limited to any specific recombinant polypeptide. The claimed invention is not adequately described because it is overly broad. The claimed invention is not commensurate in scope with the disclosure and is overly broad because claim 14 recites that the intrabody is scFv. The polypeptide of the invention is recited as binding tau, however encompasses a large genus of fragments with the recited at least 80% for example.
The polypeptide as claimed reads on many different types of polypeptides, based on the breath of the claims and encompasses a large genus. A large variable genus of products, are encompassed in the claims as well as modifications that are not described. The specification fails to provide a representative number of species for the claimed genus to show that applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described, are representative of the entire genus.
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "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). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus, 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. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
10. Claims 105 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. Claim 105 is drawn to a polypeptide, which reads on a product of nature. The claim should be amended to indicate the hand of the inventor, for example the insertion of “isolated” or "purified" in connection with the protein to identify a product not found in nature (see MPEP 2105).
11. Claim 105 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claim 105 is directed to, “a polypeptide comprising an amino acid sequence that is at least ….100% identical to any one of SEQ ID NOs 23-33… and 59-63” and does not even demonstrate the hand of man. The claim(s) does/do not include additional elements that are sufficient to amount to ‘significantly more’ than the judicial exception because the claimed invention encompasses products that have characteristics that are not markedly different from the product’s naturally occurring counterpart in its natural state.
The rationale for this determination is provided below:
The polypeptide identical to a truncated structure or a structure that is 100% identical with the activity of binding to tau. The fact pattern in the application is that the claim is directed to a product that initially appears non-naturally occurring, however is a natural product. The scope of the claims is not limited a non-naturally occurring product, thus no meaningful limits are imposed by the claim limitations to set it apart from a natural product. The judicial exception is recited with general instructions ‘that binds tau’ and a truncation in the structure. The limitations recited in claim do not change the structure to the extent that it would not be classified as non-naturally occurring especially with the recitation of 100% sequence identity. The structural truncation may influence the potential of the protein, however there are no indicia in the claims or specification that there is a marked difference in the protein structure. Although the claims may involve a transformation that results these are only tangentially related to the judicial exception as it does not implement or integrate judicial exception into a practical application. The fact that the polypeptide has percentage identity to the recited structures does not translate to an altered structure for the polypeptide, thus does not change the natural structure of the polypeptide claimed.
An analysis of the claimed invention as a whole indicates that the claims are directed to a product that on its face does not even satisfy the hand of man, and it is concluded that the product is not markedly different in structure from the naturally occurring counterpart products. The claimed invention as a whole is not informative because while the claims are limited to a particular structure, the claimed product is claimed with a very high level of generality in that it broadly encompasses the use. The claimed embodiment recites the judicial exception with a structure that involves specific percentages of sequence identity to the natural structure and there is no additional element in the claim. A truncation of a structure does not render it non-natural and the percentages reads on a 100% in the claims. There is no additional element reported in the claimed invention the makes clear that the instantly claimed polypeptide is markedly different. The claim elements are merely appended to the judicial exception and are mere field use (see Funk Brothers Seed Co., V. Kalo Inoculant Co., 333 U.S. 127, 1948 and Association for Molecular Pathology v. Myriad Genetics, Inc. 569 U.S., 133 S.Ct.2107, 2116, 106 USPQ 2d. 1972).
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.
(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.
12. Claim(s) 12-14 and 105-106 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Temple et al. (US Patent No. 11,827,683, 9/8/16, cited on IDS).
The reference teaches an anti-tau bi-functional polypeptide, comprising a polypeptide having an amino acid sequence at least 90% identical to a sequence selected from the group consisting of SEQ ID NO: 57, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, and SEQ ID NO: 72, wherein percent identity is determined using the BLASTP algorithm. It also discloses: a bi-functional polypeptide, comprising
(a) a first domain of an intrabody which binds to an epitope of Tau wherein the intrabody is an antibody fragment (scFv) including a Tau specific VL immunoglobulin domain (VL Tau) and a Tau specific VH immunoglobulin domain (VH Tau) connected by a first linker, wherein the first linker is at least 90% identical to the amino acid sequence as set forth in SEQ ID NO: 35;
(b) a second domain comprising a proteasome-targeting PEST motif having an amino acid sequence at least 90% identical to the amino acid sequence as set forth in SEQ ID NO: 38 or SEQ ID NO: 39…” (see claims 1-2 of the patent).
The patent teaches that the polypeptide binds tau, “this disclosure features bi-functional polypeptides that specifically bind to tau and their use to treat and prevent tauopathies, such as Alzheimer's disease. The bi-functional polypeptides disclosed herein comprise a first domain comprising an antigen binding domain of an antibody or antigen binding functional fragment thereof which binds to an epitope of Tau”. The reference teaches a sequence that matches the instant structure (see the below alignment). Therefore, the limitations of the claims are met by the reference.
ALIGNMENTs
RESULT 2
BFD81448
(NOTE: this sequence has 9 duplicates in the database searched.
See complete list at the end of this report)
ID BFD81448 standard; protein; 40 AA.
XX
AC BFD81448;
XX
DT 03-MAY-2018 (first entry)
XX
DE Human PEST motif peptide, SEQ ID 38.
XX
KW PEST motif; Alzheimer’s disease; antibody therapy; dementia;
KW down syndrome; frontotemporal dementia;
KW Gerstman straussler scheinker disease; neurodegenerative disease;
KW neuroprotective; Parkinson’s disease dementia;
KW progressive supranuclear palsy; protein production; protein therapy;
KW therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2018049219-A1.
XX
CC PD 15-MAR-2018.
XX
CC PF 08-SEP-2017; 2017WO-US050764.
XX
PR 08-SEP-2016; 2016US-0385019P.
XX
CC PA (REGE-) REGENERATIVE RES FOUND.
XX
CC PI Temple S, Messer A, Butler D;
XX
DR WPI; 2018-21592L/21.
XX
CC PT Single-chain bi-functional polypeptide used in composition for treating
CC PT tauopathy of patient, comprises first domain having antigen binding
CC PT domain of antibody or functional fragment which binds to epitope of Tau
CC PT and second domain.
XX
CC PS Claim 11; SEQ ID NO 38; 54pp; English.
XX
CC The present invention relates to a single-chain bi-functional
CC polypeptide, useful in a composition for treating tauopathy of a patient.
CC The polypeptide comprises a first domain having an antigen binding domain
CC of an antibody or functional fragment which binds to an epitope of Tau
CC and a second domain having a proteasome-targeting PEST motif. The
CC invention further relates to: (1) a polynucleotide encoding the single-
CC chain bi-functional polypeptide; (2) a vector, which comprises the
CC polynucleotide; (3) an isolated host cell, which is transfected with the
CC polynucleotide; (4) a method for preparing single-chain bi-functional
CC polypeptide; (5) a composition, which comprises single-chain bi-
CC functional polypeptide; (6) a kit, which comprises the single-chain bi-
CC functional polypeptide; and (7) a method for treating tauopathy of a
CC patient. The tauopathy is selected from the group consisting of Alzheimer
CC disease, Down syndrome, Guam parkinsonism dementia complex, Dementia
CC pugilistica, Pick disease, Dementia with argyrophilic grains, Fronto-
CC temporal dementia, Cortico-basal degeneration, Pallido-ponto-nigral
CC degeneration, Progressive supranuclear palsy, and Gerstmann-Straussler-
CC Scheinker disease. The present sequence is a human PEST motif peptide,
CC used in the method for preparing single-chain bi-functional polypeptide,
CC which is used in the treatment of taupathy.
XX
SQ Sequence 40 AA;
Query Match 100.0%; Score 157; Length 40;
Best Local Similarity 100.0%;
Matches 28; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 PDFPPEVEEQDASTLPVSCAWESGMKRH 28
||||||||||||||||||||||||||||
Db 2 PDFPPEVEEQDASTLPVSCAWESGMKRH 29
RESULT 3
AAM05297
(NOTE: this sequence has 9 duplicates in the database searched.
See complete list at the end of this report)
ID AAM05297 standard; protein; 47 AA.
XX
AC AAM05297;
XX
DT 09-OCT-2001 (first entry)
XX
DE Peptide #3979 encoded by probe for measuring breast gene expression.
XX
KW Probe; human; breast disease; breast cancer; development disorder;
KW inflammatory disease; proliferative breast disease; non-carcinoma tumour.
XX
OS Homo sapiens.
XX
CC PN WO200157270-A2.
XX
CC PD 09-AUG-2001.
XX
CC PF 30-JAN-2001; 2001WO-US000661.
XX
PR 04-FEB-2000; 2000US-0180312P.
PR 26-MAY-2000; 2000US-0207456P.
PR 30-JUN-2000; 2000US-00608408.
PR 03-AUG-2000; 2000US-00632366.
PR 21-SEP-2000; 2000US-0234687P.
PR 27-SEP-2000; 2000US-0236359P.
PR 04-OCT-2000; 2000GB-00024263.
XX
CC PA (MOLE-) MOLECULAR DYNAMICS INC.
XX
CC PI Penn SG, Hanzel DK, Chen W, Rank DR;
XX
DR WPI; 2001-476286/51.
XX
CC PT Novel single exon nucleic acid probe used to measuring gene expression in
CC PT a human breast.
XX
CC PS Claim 27; SEQ ID NO 14037; 322pp; English.
XX
CC The present invention relates to novel single exon nucleic acid probes
CC (see AAI00010-AAI10067). The present sequence is a peptide encoded by one
CC such probe. The probes are useful for measuring human gene expression in
CC a human breast sample, where the probe hybridizes at high stringency to a
CC nucleic acid expressed in the human breast. The probes are useful for
CC predicting, diagnosing, grading, staging, monitoring and prognosing
CC diseases of the human breast, particularly those diseases with polygenic
CC aetiology. The diseases include: breast cancer, disorders of development,
CC inflammatory diseases of the breast, fibrocystic changes, proliferative
CC breast disease and non-carcinoma tumours. Note: The sequence data for
CC this patent did not form part of the printed specification, but was
CC obtained in electronic format directly from WIPO at
CC ftp.wipo.int/pub/published_pct_sequences
XX
SQ Sequence 47 AA;
Query Match 100.0%; Score 157; Length 47;
Best Local Similarity 100.0%;
Matches 28; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 PDFPPEVEEQDASTLPVSCAWESGMKRH 28
||||||||||||||||||||||||||||
Db 9 PDFPPEVEEQDASTLPVSCAWESGMKRH 36
Conclusion
13. No claims are presently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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, Robert Mondesi can be reached on (408) 918-7584. 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.
/HOPE A ROBINSON/Primary Examiner, Art Unit 1652