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 10, 12, 18, have been canceled. Claims 1-5 and newly added claims 22-23 are still at issue and are present for examination.
Claims 6-9, 11, 13-17, 19-21 are withdrawn, as drawn to non-elected subject matter.
Applicants' arguments filed on 2/5/26, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 1-5 and newly added claims 22-23, drawn to species 7 (a peptide comprising SEQ ID NO:2 and variants thereof) and drawn to a peptide having two physiologically active portions that are identical, placed on either side of a linker are under examination.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim(s) 1-3, 22-23, are rejected under 35 U.S.C. 103 as being unpatentable over Binder et al., “Binder” (US 2019/0010192, 1/2019). Binder in its abstract, recites the following: “This invention relates to a nucleic acid molecule comprising a low repetitive nucleotide sequence encoding a proline/alanine-rich amino acid repeat sequence. The encoded polypeptide comprises a repetitive amino acid sequence that forms a random coil. The nucleic acid molecule comprising said low repetitive nucleotide sequences can further comprise a nucleotide sequence encoding a biologically or pharmacologically active protein. Further, the present invention provides for selection means and methods to identify said nucleic acid molecule comprising said low repetitive nucleotide sequence. This invention also relates to a method for preparing said nucleic acid molecules. Also provided herein are methods for preparing the encoded polypeptide or drug conjugates with the encoded polypeptide using the herein provided nucleic acid molecules. The drug conjugate may comprise a biologically or pharmacologically active protein or a small molecule drug. Also provided herein are vectors and hosts comprising such nucleic acid molecules”.
In [365], according to Binder, the amino acid residues comprised in the encoded peptide or protein may, e.g., be present as a linear molecular chain (forming a linear peptide or protein) or may form one or more rings (corresponding to a cyclic peptide or protein), e.g., circularized via a peptide or is peptide bond or a disulfide bridge. The peptide or protein may also form oligomers consisting of two or more identical or different molecules. As used herein, the term “domain” relates to any region/part of an amino acid sequence that is capable of autonomously adopting a specific structure and/or function. In the context of the present invention, accordingly, a “domain” may represent a functional domain or a structural domain, which may for example form part of a larger polypeptide.
In Table 1, low repetitive nucleotide sequences of Binder encode expression products (see SEQ ID NO:1-2) which are 19 and 20 amino acids in length, respectively and are AP rich sequences having two or more AP repeats.
In [0238-0240], Binder discloses that:
“[0230] The person skilled in the art understands that the steps of this method can be iteratively repeated until the desired length of the assembled nucleotide sequence or the assembled nucleic acid molecule encoding the PA-rich polypeptide is obtained.
[0239] In order to provide means and methods to advantageously clone the nucleic acid molecules provided herein, a suitable cloning vector comprises an upstream recognition sequence that is recognized by an endonuclease restriction enzyme and a downstream recognition sequence that is recognized by an endonuclease restriction enzyme, wherein optionally said endonuclease restriction enzyme recognizing said downstream recognition sequence is different from said endonuclease restriction enzyme recognizing said upstream recognition sequence, wherein said upstream recognition sequence and said downstream recognition sequence are in a reverse complementary orientation. Further, said upstream recognition sequence can comprise two recognition sequences for two different restriction enzymes. Further, said downstream recognition sequence can be comprised in the upstream recognition sequence. Thus, said downstream recognition sequence can be comprised in one of the upstream recognition sequences. The appended illustrative examples show the exemplary vectors and nucleic acids molecules as well as methods to provide those, in particular, FIGS. 1, 4, 6 and 8.
[0240] It is documented in the appended examples that it is particularly beneficial that the downstream recognition sequence is comprised in the upstream recognition sequence. By using such a strategy, the upstream recognition site may be employed to assemble further nucleotide sequences into the vector provided herein. Of course, the positions of the upstream and downstream restriction sites on such a vector are interchangeable. An exemplary cloning region with an inserted inventive nucleotide sequence is shown in FIG. 1D. In this instance, the restriction enzyme recognizing the downstream recognition sequence (which is equivalent to first physiologically active peptide portion) also recognizes and cleaves the upstream recognition sequence (which is equivalent to send physiologically active peptide of this invention). Therefore, the inventive nucleotide sequence or the nucleic acid molecule encoding the polypeptide consisting of proline, alanine and, optionally, serine may be excised from the vector provided herein by employing the restriction enzyme recognizing said downstream and upstream recognition sequence, thus allowing use for ligation with other nucleic acids or vectors, e.g. to allow gene expression or to create a coding region for a fusion protein. An example for this cloning strategy to achieve assembly of a long low repetitive nucleotide sequence is illustrated herein below; see e.g. FIG. 1E”.
In claim 30, Binder lists a series of biologically active peptides wherein many of said products can be up to 50 amino acids in length (such as insulin analogs) and many of them are receptors (such as EGF receptor) that inherently can be activated by dimerization.
Therefore, given the teachings of Binder, one of ordinary skill in the art can readily envisage a fusion DNA sequence encoding:
(1) a proline rich sequence having 19-20 amino acids in length (that can be considered to be a linker sequence) attached to a
(2) DNA sequence encoding a first physiologically active peptide namely an enzyme recognition site or DNA encoding a “biologically active” protein (said DNA sequence optionally encoding a ring or circular product) of Binder, wherein said DNA encoding the proline rich sequence may optionally be attached to
(3) DNA fragment encoding a restriction enzyme restriction site (second physiologically active peptide) at its other end and expression product of said fusion DNA, rendering this invention obvious.
Finally, one of ordinary skill in the art has a reasonable expectation of success to preparing a fusion DNA as described above in view of Binder because procedures for producing such expression products were fully established in the prior art, before the effective filing of this application.
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 1-5, 22-23 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. Claim 1 (and its dependent claims 2-5, 22-23) are directed to a genus of peptide fusion molecules of any length or any amino acid sequence composition (optionally made of one or more cyclic structures) comprising a linker portion of up to 49 amino acids, wherein said linker comprises two or more repeats of AP, AAP, AS, ASP or ASS, wherein said fusion products are inadequately described in terms of structure, in the disclosure.
The specification fails to teach what the final size of such fusion peptide molecules are. The only structural information provided in claim 1, is directed to the linker peptide, which may be up to 49 amino acids in length, made up of mainly proline, alanine and serine residues. Considering that instantly claimed fusion peptides may be 20,000 or more amino acids in length, it is totally unclear how such fusion peptide with for example, a single linker of up to 49 amino acids may be prepared such that it will optionally comprise cyclic peptides that have inflammatory disease, respiratory disease (see page 94 of the specification)” treatment” properties, whatever that treatment specifically is.
Further, in claim 2, applicant recites that at least one of said “physiologically active portions” may be cyclic. However, the specification fails to teach when the fusion peptide molecules are made of cyclic and random coil portions what should the optical length of the linker used may be and how many linkers may be needed.
Furthermore, the prior art is unpredictable as to which hosts are suitable to express polypeptides of for example, 20,000 amino acids in length, which may be cyclic or partially cyclic with such a short linker such that their expression product results in a peptide that would retain the desired “disease treating function” whatever that treatment may be.
Given the breadth of these claims, some more structural information as to how many copies of each of physiologically active peptide portions (both random coli and cyclic) and how many linkers of up to 49 amino acids made of AP, AAP, AS etc. and whether said linkers need to be identical or not such that they constitute a fusion polypeptide that retains its “disease treating function”, deems necessary that is currently lacking in the disclosure.
In claim 5, some embodiments of such “physiology active cyclic peptides” are provided (see SEQ ID NOs:1-6 and claimed variants thereof, but said claim fails to specify up to how many copies of said cyclic peptides and how many linkers may be incorporated into the fusion molecules of this invention.
Similarly in claim 22, applicant has recited the length of the first and second “physiologically active portions” to be 3-50 amino acids but again fails to recite how many copies of each portion may be within the scope of said claim and whether said “physiologically active portions” are cyclic or random coil.
Similarly in claim 23, it is unknown what is the size, composition and length of the “target-binding peptide” and how many copies of said “target-binding peptide” constitute the fusion peptide, such that its “treats” the target disease.
Therefore, given the information provided in the disclosure, one of ordinary skill in the art cannot reasonably conclude that applicant had full possession of this invention, before the effective filing of this application.
No claim is allowed.
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 MARYAM MONSHIPOURI whose telephone number is (571)272-0932. The examiner can normally be reached full-flex.
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, Melenie L Gordon can be reached at 571-272-8037. 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.
/MARYAM MONSHIPOURI/Primary Examiner, Art Unit 1651
Prosecution Insights