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 .
DETAILED ACTION
Application status
Claims 44-63 are pending in this application.
Priority
The instant application is the 371 national stage entry of PCT/IL2021/051017, filed on 08/19/2021, which claims benefit of 63069080 filed on 08/23/2020.
Election
Applicant's election without traverse of Group I, Claims 44-57 in the response filed on 10/28/2025, and a species IGF1 on 03/05/2026, is acknowledged.
Claims 58-63 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention.
For the reasons provided above, this restriction requirement is deemed proper, and therefore, it is made final.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/03/2023 and 03/12/2024 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 47-48 and 55 are objected to because of the following informalities:
Claim 48 is objected to for the recitation of “claims 44”. The Examiner suggests replacing the noted phrase with ---claim 44---.
Claims 47 and 55 are objected to because the recitation of abbreviations “FGF2, IGF1, TGF31, EGF, LIF, … NRG1, PDGF, IL6, IL13” which should be in parenthesis and follow the actual terms it abbreviates when used for the first time in a claim.
Appropriate correction is required.
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 44, 46 and 50 are rejected under 35 U.S.C. 112(b), as failing to set forth 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 44 recites the phrase “and at least one layer and/or fiber of cellulose…” which is unclear. It is not clear as to what “at least one layer” is referring to because it is immediately followed by the word “and/or”. In the interest of advancing prosecution, the noted phrase is interpreted as ---and at least one layer of fiber of cellulose---.
Claim 46 recites the phrase “other protein required for cell viability like transferrin” is unclear (italicized for added emphasis). It is unclear because one cannot determine if the limitation following the “like” is part of the claimed invention. See MPEP § 2173.05(d). Furthermore, it is unclear what the metes and bounds of “other protein required for cell viability like transferrin” is because there is no guidance on what structural features are required in those ‘other protein’ to be like transferrin. In the interest of advancing prosecution, the noted phrase is interpreted as “any protein required for cell viability”.
Claim 50 recites the phrase “at least two layers and/or fibers of cellulose…” which is unclear. It is not clear as to what “at least two layers” are referring to because it is immediately followed by the word “and/or”. In the interest of advancing prosecution, the noted phrase is interpreted as ---at least two layers of fiber of cellulose---.
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 44-46 and 52-54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Doheny et al. (Cellulose as an inert matrix for presenting cytokines to target cells: production and properties of a stem cell factor–cellulose-binding domain fusion protein. Biochemical Journal, 339(2), 429-434, 1999, see IDS) in view of an evidentiary reference of Poon et al. (THE JOURNALOFBIOLOGICALCHEMISTRY VOL.282, NO. 3, pp. 2091–2100, January 19, 2007).
The instant claims are drawn to an in-vitro tissue engineering system comprising a chimeric polypeptide and at least one layer and/or fiber of cellulose, wherein the chimeric polypeptide comprises a cellulose binding domain (CBD), a cell effector protein (CEP); and a linker linking the CBD to the CEP.
Doheny et al. teach an in-vitro tissue engineering system comprising a chimeric polypeptide and layers of cellulose, wherein the chimeric polypeptide comprises a cellulose binding domain (CBD) linked to a proline/threonine-rich linker from xylanase Cex, which is linked to a cell effector protein (CEP), i.e., stem cell factor (SCF) (see Abstract; Figure 1A on page 430; and page 431, right column, last para). Doheny et al. teach that the SCF is a cytokine (see Abstract).
The evidentiary reference of Poon et al. teach that the proline/threonine-rich linker from xylanase Cex is 20 amino acids long (see Figure 1 on page 2092).
Therefore, teachings of Donehy et al. anticipate Applicants’ claimed invention.
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 44-57 are rejected under 35 U.S.C. 103 as being unpatentable over Doheny et al. (Cellulose as an inert matrix for presenting cytokines to target cells: production and properties of a stem cell factor–cellulose-binding domain fusion protein. Biochemical Journal, 339(2), 429-434, 1999) in view of Li et al. (Modified insulin-like growth factor 1 containing collagen-binding domain for nerve regeneration. Neural Regen Res 13(2):298-303, 2018), Shoseyov et al. (US Patent No. 5670623), Yu et al. (Tobacco etch virus protease mediating cleavage of the cellulose-binding module tagged colored proteins immobilized on the regenerated amorphous cellulose, Bioprocess Biosyst Eng 40:101-1110, 2017, see IDS), an evidentiary reference of Poon et al. (THE JOURNALOFBIOLOGICALCHEMISTRY VOL.282, NO. 3, pp. 2091–2100, January 19, 2007), and KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007).
The instant claims are drawn to an in-vitro tissue engineering system comprising a chimeric polypeptide and at least one layer and/or fiber of cellulose, wherein the chimeric polypeptide comprises a cellulose binding domain (CBD), a cell effector protein (CEP); and a linker linking the CBD to the CEP.
Teachings of Doheny et al. is as described above.
Doheny et al. do not teach [1] the use of a linker linking the CBD to the CEP which can be cleaved by a site-specific protease, and [2] the at least one layer comprising at least two types of chimeric polypeptides, each comprising different CEP.
Li et al. teach a chimeric polypeptide comprising a cellulose binding domain (CBD) and a cell effector protein (CEP), wherein CEP is IGF1 (see page 298, Graphical Abstract). Li et al. also indicate that the chimeric polypeptide exhibited biological activities, i.e., increasing cell proliferation and neural differentiation of PC12 cells in vitro (see page 302 both left and right columns).
Shoseyov et al. teach an in-vitro tissue engineering system comprising a cellulose fiber comprising a chimeric CBD-protease cleavable linker-CEP protein, i.e. a second protein, wherein said second protein is selected from the group consisting of Protein A, Protein G, streptavidin, avidin, Taq polymerase, non-Taq polymerases, alkaline phosphatase, RNase, DNase, restriction enzymes, peroxidates, glucanases, chitinases, beta and alpha glucosidases, beta and alpha glucoronidases, amylase, transferases, beta-lactamase, non-beta lactamase antibiotic modifying and degrading enzymes, luciferase, esterases, lipases, proteases, bacteriocines, antibiotics, enzyme inhibitors, growth factors, hormones, receptors, antigens, membranal proteins, nuclear proteins, transcriptional and translational factors and nucleic acid modifying enzymes (see claims 1 and 5-7; and column 20, lines 25-35).
Yu et al. teach a Tobacco etch virus (TEV) protease cleavage of a linker at a predetermined cleavage efficiency, such that when the chimeric polypeptide is exposed to the protease, a sustained release of the tagged colored protein from the CBD is obtained, (see Fig. 1-3 on pages 1105-1106), wherein the cleavage site is a cleavage site of a protease having a catalytic efficiency (kcat/KM) of 0.2100 or 0.1422 mM-1S-1 (see Table 1 on page 1105).
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the instant application to make and use the in-vitro tissue engineering system comprising a chimeric polypeptide and layers of cellulose, wherein the chimeric polypeptide comprises CBD-proline/threonine-rich linker-SCF as taught by Doheny et al. and replace [1] the proline/threonine-rich linker with a linker comprising a TEV protease cleavage site as taught by Yu et al., and [2] the SCF with various grow factors, cytokines, including IGF1 as taught by Li et al. and Shoseyov et al., thereby making multiple layers of cellulose each comprising different CEPs.
A POSITA would have been motivated to make and use such composition because [1] Doheny et al., Li et al., and Shoseyov et al. demonstrated that such in-vitro tissue engineering system for immobilizing the chimeric protein using cellulose as an inert matrix increases sustained presentation of cytokines/growth factors compared to using soluble cytokines/growth factors (for example see Figure 5 of Doheny et al. on page 433), and [2] replacing the proline/threonine-rich linker with a linker comprising a TEV protease cleavage site provides a standard tool for tunable release as taught by Yu et al.
As discussed in KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007), it is considered obvious to combine prior art elements known to be used in equivalent fields of endeavor together into a single combination. The references clearly show that [1] CEPs, i.e., SCF, IGF1, Protein A, Protein G, streptavidin, avidin, Taq polymerase, non-Taq polymerases, alkaline phosphatase, RNase, DNase, restriction enzymes, peroxidates, glucanases, chitinases, beta and alpha glucosidases, beta and alpha glucoronidases, amylase, transferases, beta-lactamase, non-beta lactamase antibiotic modifying and degrading enzymes, luciferase, esterases, lipases, proteases, bacteriocines, antibiotics, enzyme inhibitors, growth factors, hormones, receptors, antigens, membranal proteins, nuclear proteins, transcriptional and translational factors and nucleic acid modifying enzymes, as taught by Doheny et al., Li et al., and Shoseyov et al.; and [2] the peptide linkers, i.e., the proline/threonine-rich linker, and a linker comprising a TEV protease cleavage site, were known to be used in equivalent fields of endeavor; thus, it is considered obvious to combine them together into various chimeric polypeptides with basic structure comprising CBD-linker-CEP to be used with the cellulose layers.
A POSITA would have had a reasonable expectation of success to make and use such composition because all of the required biochemical reagents and techniques were readily available and rampantly used as evidenced by Doheny et al., Li et al., Shoseyov et al., Poon et al. and Yu et al. prior to the filing of the instant application.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Conclusion
Claims 44-57 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
The instant Office action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656