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 with traverse of Group I (i.e., claims 1, 17, 21, 32-38, 40, and 42-49 directed to fibronectin type III domain fusion protein) in the reply filed on June 25, 2024, is acknowledged. Additionally, Applicant's election with traverse of Species A (i.e., a fibronectin type III domain fusion protein as fibronectin type 7 III domain (FN7) where the FN is human FN7 and having the sequence of SEQ ID NO: 2, a flexible peptide that is GGSGGGGSGGGGSGGGGS or GGGGSGGGSGGGGSGGSG, a growth hormone as the first physiologically active peptide that is inserted at the CD loop, and a Fc as a second physiologically active peptide that is inserted at the EF loop) in the reply filed on June 25, 2024, is acknowledged. The traversal is on the grounds that the technical feature defines the positional relationship between the first physiologically active peptide, the fibronectin type III domain, and the one or more linkers such that the peptide is inserted within the flexible loop of the fibronectin type III domain through the one or more linkers (See Applicant’s Response received on 6/25/24, pg. 12). However, CN108179152A replaces the sequence of the FG loop with a proBNP peptide fragment, and fuses another proBNP peptide fragment to the C-terminus of fibronectin type III domain (See Applicant’s Response received on 6/25/24, pg. 13). Thus, the instant first physiologically active peptide is not inserted within a flexible loop through the one or more linkers (See Applicant’s Response received on 6/25/24, pg. 13).
Applicant’s argument is found persuasive. However, the technical feature shared between the groups as indicated by Applicants, lacks unity of invention in light of Zauderer et al. US Publication No. 2002/0192675 A1 published on December 19, 2002. Please note that the technical feature lacks unity of invention for the reason set forth below in the 103 rejection. Thus, lack of unity remains.
Additionally, please note that the Species election with respect to the location the first and second physiologically active polypeptides are inserted, with respect to the first and second physiologically active polypeptides, and with respect to the type of FN3 domain is hereby withdrawn.
Status of Claims
Claims 1-42 were originally filed on January 17, 2021.
The amendment received on January 18, 2021, canceled claims 2-16, 18-20, 22-31, 39, and 41; and amended claims 1, 17, 21, 32-33, 36-38, 40, and 42; and added new claims 43-49. The amendment received on June 25, 2024, amended claims 1, 17, 21, 38, 42, and 48-49.
Claims 1, 17, 21, 32-38, 40, and 42-49 are currently pending and claims 1, 17, 32, 38, 40, and 42-49 are under consideration as claims 33-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, and claims 21, 44, 47, and 49 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on June 25, 2024.
Priority
The present application claims status as a 371 (National Stage) of PCT/CN2019/096357 filed July 17, 2019, and claims priority under 119(a)-(d) to Chinese Application No. 201810784128.X filed on July 17, 2018.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for Chinese Application No. 201810784128.X, which papers have been placed of record in the file. Please note that the Chinese application is NOT in English and therefore cannot be verified.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on January 18, 2021; July 21, 2022; and April 10, 2024, are being considered by the examiner.
Sequence Interpretation
Regarding claim 17, please note that the Examiner is interpreting the scope as closed-ended requiring 100% identity with the same length to one of the recited sequences.
Regarding claim 32, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to one of the recited sequences with any N- and/or C-terminal additions.
Regarding claims 40 and 45-46, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to one of the recited sequences with any N- and/or C-terminal additions.
Drawings
Figure 3 is objected to because it depicts a sequence alignment of different fibronectin type III domains without indicating a sequence identifier for each sequence. However, it is noted that the SEQ ID NOs: need to be present in either the figure or the Brief Description of the Drawings. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Drawings
The drawings; in particular, Figure 3, are objected to because of the following reason:
The drawings have a line quality that is too light to be reproduced (weight of all lines and letters must be heavy enough to permit adequate reproduction) or text that is illegible (reference characters, sheet numbers, and view numbers must be plain and legible) see 37 CFR 1.84(l) and (p)(1)); See Figure 3.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: on page 8, item 20; page 9, item 23; and page 19, 1st paragraph, discusses a C-peptide fragment (i.e., EVARQ) without an accompanying SEQ ID NO. Pursuant to MPEP 2422 and 37 CFR 1.821(a), any amino acid sequence at least 4 amino acids in length requires a sequence identifier. Additionally, please update the Sequence Listing, if necessary.
Appropriate correction is required.
Sequence Compliance
Applicant is advised that the application is not in compliance with 37 CFR §§ 1.821-1.825.
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR §§ 1.821-1.825 for the reason(s) set forth below. Applicant must comply with the requirements of the sequence rules (37 CFR §§ 1.821- 1.825) in order to completely respond to this office action.
The specification and claims depict and/or recite sequences without a sequence identifier. More specifically, as discussed supra, Figure 3 depicts amino acid sequences, and in the specification at pgs. 8-9 and 19. Moreover, as discussed below, claim 17 depicts amino acid sequences without a sequence identifier. In order to satisfy the sequence rules requirements, Applicant needs to provide an amendment to the instant claims and specification to include reference to the appropriate sequence identifier “SEQ ID NO:” in parenthesis next to each of the sequences having 4 or more defined amino acids. Please confirm that all peptides having 4 or more than 4 defined amino acid residues have sequence identifiers and are included in the sequence listing.
In case of any new sequences not properly identified in the instant specification and/or claims, Applicant is required to provide a substitute computer readable form (CRF) copy of a “Sequence Listing” which includes all of the sequences that are present in the instant application and encompassed by these rules, a new or substitute paper copy of that “Sequence Listing”, an amendment directing the entry of that paper copy into the specification, and a statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R. § 1.821(e) or 1.821(f) or 1.821(g) or 1.825(d). The instant specification will also need to be amended so that it complies with 37 C.F.R. § 1.821(d) which requires a reference to a particular sequence identifier (SEQ ID NO:) be made in the specification and claims wherever a reference is made to that sequence. For rules interpretation Applicant may call (571) 272-2533. See M.P.E.P. 2422.04.
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Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites “…between two adjacent β chains selected from the group consisting of AB loop, BC loop, DE loop, EF loop or FG loop…" It is respectfully requested that claim 1 recites, “…between two adjacent β chains selected from the group consisting of AB loop, BC loop, DE loop, EF loop and FG loop…" Alternatively, Applicants can indicate a proper Markush claim as ““…between two adjacent β chains comprising AB loop, BC loop, DE loop, EF loop or FG loop…" See MPEP § 2173.05(h). Appropriate correction is required.
Claim 17 is objected to because of the following informalities: the claim recites amino acid sequences as flexible linkers where the sequences have at least 4 defined amino acid residues. Pursuant to MPEP 2422 and 37 CFR 1.821(a), any amino acid sequence at least 4 amino acids in length requires a sequence identifier. Thus, it is respectfully requested that the sequences depicted in instant claim 17 are accompanied by a sequence identifier. Additionally, please include a Sequence Listing. Appropriate correction is required.
Claims 42 and 48 are objected to because of the following informalities: the claims recite, “Fc”. It is respectfully requested that the claims recite “Fc region” in order to be grammatically correct to indicate that it is a Fc region being claimed. 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.
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 17, 40, 43, 45-46, and 48 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. Regarding claims 17, 43, 45-46, and 48, the phrase "preferably", and/or “more preferably” and/or “such as” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Regarding claim 40, the phrase "in particular" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Please note that the Examiner is interpreting that the limitations following the phrases are optional, but not required in order to advance prosecution.
Claim 43 is 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 is directed to where the fusion protein further comprises a second physiologically active peptide that is inserted within a flexible loop of the FN3 that is at a different position than the first physiologically active peptide or where the second physiologically active peptide is linked to the N-terminal or the C-terminal of the FN3 domain by the linker. However, claim 43 is dependent upon claim 17, which is dependent upon claim 1. Claim 1 requires that the one or more linkers fuse the first physiologically active peptide within a flexible loop of the FN3. Thus, it is unclear how the linker referred to in claim 43 (i.e., referring back to the one or more linkers in claim 1) can link the first physiologically active peptide to a loop of the FN3 and the second physiologically active peptide to a termini of the FN3.
Please note that the Examiner is interpreting the scope of claim 43 such that if the second physiologically active peptide is linked a termini of the FN3, it is via a different flexible peptide linker than the linker in claim 1 in order to advance prosecution.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1, 17, 38, 43 are rejected under 35 U.S.C. 103 as being unpatentable over Zauderer et al. US Publication No. 2002/0192675 A1 published on December 19, 2002, in view of Koide et al., J. Mol. Biol. 284:1141-1151 (1998).
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claims 1, 17, and 43, with respect to a fibronectin type III domain fusion protein comprising a fibronectin type III domain (FN3 domain), one or more linkers, and a first physiologically active peptide inserted within a flexible loop formed between two adjacent β chains selected from AB loop, BC loop, CD loop, DE loop, EF loop, and FG loop of the FN3 domain through the one or more linkers as recited in instant claim 1; with respect to where at least one linker in the fusion protein is a flexible peptide where the flexible peptide is a polypeptide having a flexible structure as recited in instant claim 17; and with respect to where the FN3 domain fusion protein further comprises a second physiologically active peptide that is inserted within a flexible loop formed between two adjacent β chains selected from AB loop, BC loop, CD loop, DE loop, EF loop, and FG loop of the FN3 domain, and where the first and second peptides are inserted at different positions of the FN3 domain as recited in instant claim 43:
Zauderer et al. teaches isolated regulator molecules, compositions comprising isolated regulator molecules, and a library of polynucleotides constructed to express candidate regulator molecules (See Zauderer specification, [0052]). The regulator molecules can be candidate regulator molecules, which are products that can be tested for the ability to alter the phenotype of a cell (See Zauderer specification, [0070]). Regulatory polypeptide expression can influence activation of a target transcriptional regulatory region in an eukaryotic hose cell (See Zauderer specification, [0055]; claims 49, 51, 96) thereby constituting where the regulatory polypeptide is a physiological active polypeptide.
The candidate regulator molecules are candidate regulator polypeptides, which comprise at least two components, a “candidate peptide” and a “molecular scaffold” (See Zauderer specification, [0071]). Zauderer et al. also teaches that a regulator polypeptide can comprise one or more candidate peptides (See Zauderer specification, [0071]) thereby encompasses more than one peptides. Molecular scaffolds maintain the candidate peptides in a conformationally restricted or stable form where the candidate peptide is preferably situated on an exposed surface of a molecular scaffold protein such that the candidate peptides can interact with cellular elements (See Zauderer specification, [0071], [0073]). The presentation of peptides in conformationally constrained structures will benefit both the later generation of pharmaceuticals and will also likely lead to higher affinity interactions of the polypeptide with the target protein (See Zauderer specification, [0073]). The candidate regulator polypeptide is inserted into the molecular scaffold where a first portion is joined to the N-terminal end of the candidate peptide and a second portion joined to the C-terminal end of the candidate peptide (See Zauderer specification, [0074]) thereby constituting where the peptide is inserted into a molecular scaffold. It is preferred that the peptide is presented on an exterior loop of the molecular scaffold (See Zauderer specification, [0075]). Zauderer et al. teaches that a FN3 domain is an example of a molecular scaffold where the BC loop, the FG loop and the terminal tail can be randomized (See Zauderer specification, [0080], [0213]) thereby constituting a FN3 domain. In Example 6, Zauderer et al. teaches generating a cDNA library encoding random peptide sequences (i.e., candidate regulatory polypeptides) in the scaffold of the FN3 domain where a random peptide sequence is inserted at residues 29 (Val) and 30 (Thr), the second and third residues of the BC loop, and/or at residues 78-80, the second, third, and fourth residues of the FG loop of the FN3 domain (See Zauderer specification, [0321]). This library is constructed to contain a minimum of 3x106 clones in order to ensure complete sampling of all combinations randomized residues in both BC and FG loops (See Zauderer specification, [0321]; claims 11-12) thereby constituting a first peptide inserted in the BC loop and a second peptide inserted in the FG loop. Thus, Zauderer et al. teaches a FN3 domain as a molecular scaffold that is modified by inserting a regulatory polypeptide comprising one or more peptides into the scaffold such that a first peptide of the regulatory polypeptide is inserted into the BC loop and a second peptide of the regulatory polypeptide is inserted into the FG loop thereby forming a FN3 domain fusion protein.
Regarding one or more linkers, Zauderer et al. teaches that a heterologous polypeptide fusion partner (i.e., a fusion protein comprising the candidate regulator polypeptide to a heterologous sequence such as a nuclear localization sequence, targeting sequence, or membrane-anchoring sequence) includes a linker or tethering sequence (See Zauderer specification, [0085]-[0100], [0112]). It is noted that the instant first and second physiological active peptides can also be considered the fusion partner as the heterologous sequence similarly exhibits physiological activity. Linker sequences between various targeting sequences (for example, membrane targeting sequences) and the other components of the constructs (such as the candidate peptides or molecular scaffold polypeptides) may be desirable to allow the candidate regulator polypeptides to interact with potential targets unhindered (See Zauderer specification, [0112]). Zauderer et al. teaches that useful linkers include glycine-serine polymers including, for example, (GS)n (SEQ ID NO: 70), (GSGGS)n (SEQ ID NO: 71) and (GGGS)n (SEQ ID NO: 72) where n is an integer of at least one (See Zauderer specification, [0112]). Glycine-serine polymers are preferred since both of these amino acids are relatively unstructured, and therefore, can be able to serve as a neutral tether between components (See Zauderer specification, [0112]). Given that instant claim 17 identifies that a flexible peptide consists of small molecular weight polar amino acids such as glycine or serine, the useful linkers taught by Zauderer necessarily constitute a flexible linker as recited in instant claim 17. Thus, the teachings of Zauderer et al. suggest a FN3 domain fusion protein comprising a regulatory polypeptide comprising one or more regulatory peptides as a first and second peptide that is inserted into a FN3 domain as a molecular scaffold where a first peptide is inserted into the BC loop and the second peptide is inserted into the FG loop and where each peptide is fused to the FN3 loop via a flexible peptide that has a flexible structure as recited in instant claims 1, 17, and 43.
For claim 38, with respect to a pharmaceutical composition comprising the FN3 domain fusion protein of claim 1 and a pharmaceutically acceptable carrier:
Zauderer et al. teaches a composition comprising the regulator polypeptide and a pharmaceutically acceptable carrier (See Zauderer claims 50, 97). Therefore, the teachings of Zauderer et al. satisfy the claim limitations as recited in instant claim 38.
For claims 40 and 45-46, with respect to where the FN3 domain is a FN 10th type III domain:
Zauderer et al. refers to the molecular scaffold being FN3 as described in Koide et al. 1998 (See Zauderer specification, [0112], [0213]). However, Zauderer et al. does not expressly teach or suggest where the FN3 domain is a FN type 10 III domain where the FN10 is human FN10.
Koide et al. reports the isolation of novel binding proteins used as a scaffold consisting of the FN3 domain (See Koide article, pg. 1142, col. 1, last paragraph). In many cases ligand binding sites are formed by surface loops suggesting that the FN3 scaffold is an effective framework onto which loops for specific building functions can be grafted (See Koide article, pg. 1142, col. 1, last paragraph). To examine FN3 as an effective scaffold, Koide et al. built their system on the 10th FN3 unit of human fibronectin (See Koide article, pg. 1142, col. 1, last paragraph). Therefore, since Zauderer et al. refers to the FN3 domain utilized in Koide et al., an ordinary skilled artisan would be motivated to utilize the FN 10th type III domain as the molecular scaffold as recited in instant claims 40 and 45-46.
For claim 42 and 48, with respect to where the first physiologically active peptide is :
As discussed supra, Zauderer et al. teaches that regulatory polypeptide expression can influence activation of a target transcriptional regulatory region in an eukaryotic host cell (See Zauderer specification, [0055]; claims 49, 51, 96). Moreover, Zauderer et al. teaches that a heterologous polypeptide fusion partner (i.e., a fusion protein comprising the candidate regulator polypeptide to a heterologous sequence such as a nuclear localization sequence, targeting sequence, or membrane-anchoring sequence (See Zauderer specification, [0085]-[0100], [0112]). Examples of membrane-anchoring sequences include a GPI anchor sequence (See Zauderer specification, [0093]), a transmembrane domain derived from CD8, ICAM-2, IL-8R, CD4, LFA-1, and IL-2 receptor beta-chain (See Zauderer specification, [0091]-[0092]). Since the instant claim does not exclude where the first physiologically active peptide can be part of a fusion protein, and Zauderer et al. teaches a membrane-anchoring sequence as a heterologous fusion partner of the regulatory peptide that can also constitute the instant first physiologically active peptide thereby constituting a structural protein. Therefore, the teachings of Zauderer et al. suggest inserting a structural protein as a first physiologically active peptide as recited in instant claims 42 and 48.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Zauderer et al. does not expressly teach a single embodiment of a FN3 domain comprising a FN3 domain, one or more linkers, and a first physiologically active peptide inserted within the BC loop of the FN3 domain through the one or more linkers as recited in instant claim 1; where the linker is a flexible peptide as recited in instant claim 17; where the FN3 domain is a human FN10 as recited in instant claims 40 and 45-46; where the first physiologically active peptide is a structural protein as recited in instant claims 42 and 48; and where the FN3 domain further comprises a second physiologically active peptide that is inserted within a FG loop of the FN3 domain as recited in instant claim 43. However, the combined teachings of Zauderer et al. and Koide et al. cure these deficiencies by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to a FN3 domain comprising a FN3 domain, one or more linkers, and a first physiologically active peptide inserted within the BC loop of the FN3 domain through the one or more linkers as recited in instant claim 1; where the linker is a flexible peptide as recited in instant claim 17; where the FN3 domain is a human FN10 as recited in instant claims 40 and 45-46; where the first physiologically active peptide is a structural protein as recited in instant claims 42 and 48; and where the FN3 domain further comprises a second physiologically active peptide that is inserted within a FG loop of the FN3 domain as recited in instant claim 43, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of Zauderer et al. and generate a fusion protein comprising a first physiologically active peptide as a heterologous polypeptide fusion partner comprising a fusion protein of a candidate regulator polypeptide and a heterologous sequence such as a GPI anchor or a transmembrane domain derived from CD8, ICAM-2, IL-8R, CD4, LFA-1, and IL-2 receptor beta-chain that is inserted in the BC loop of a human FN10 via a flexible peptide linker and a second physiologically active peptide as a heterologous polypeptide fusion partner comprising a fusion protein of a candidate regulator polypeptide and a heterologous sequence that is inserted within the FG loop of the human FN10. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the human FN10 scaffold was known to be an effective framework onto which loops for specific building functions can be grafted as taught by Koide et al.; because molecular scaffolds were known to maintain the candidate peptides in a conformationally restricted or stable form where the candidate peptide is preferably situated on an exposed surface of a molecular scaffold protein such that the candidate peptides can interact with cellular elements, and cause flexible peptide linkers were known to allow the candidate regulator polypeptides to interact with potential targets unhindered as taught by Zauderer et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the fusion protein comprising a candidate regulatory polypeptide comprising one or more candidate regulatory peptides, each of which inserted into a molecular scaffold of Zauderer et al. was known to be used in a screening method to identify polypeptides able to influence activation of a target transcriptional regulatory region in an eukaryotic hose cell. Therefore, utilizing a heterologous polypeptide fusion partner comprising a fusion protein of a candidate regulator polypeptide and a heterologous sequence such as a GPI anchor or a transmembrane domain derived from CD8, ICAM-2, IL-8R, CD4, LFA-1, and IL-2 receptor beta-chain that is inserted in the BC loop of a human FN10 via a flexible peptide linker and a second physiologically active peptide as a heterologous polypeptide fusion partner comprising a fusion protein of a candidate regulator polypeptide and a heterologous sequence that is inserted within the FG loop of the human FN10 would support the maintenance of the candidate peptides in a conformationally restricted or stable form where the candidate peptide is preferably situated on an exposed surface of a molecular scaffold protein such that the candidate peptides can interact with cellular elements by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Allowable Subject Matter
Claim 32 is 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. It is noted that there is no teaching or suggestion in the art to result in the specific fusion protein sequences as recited in instant claim 32.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654