DETAILED ACTION
Claims 5, 14, 16-17 and 19 were/stand cancelled. Claims 1-4, 6-13, 15, 18, 20-25 are pending.
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 .
Priority
This application is a 371 of PCT/EP2021/067255 (06/23/2021) which claims priority to UNITED KINGDOM 2009710.1 (06/25/2020) as reflected in the filing receipt issued on June 6 2024.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 20 2022 and December 12 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because: 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."” In the current case, the view numbers for Figures 1-2 are preceded by the word "Figure" instead of the abbreviation "FIG.".
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.
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 6, 9-10 and 15 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 6 as currently written is vague and indefinite. The claim recites the anchoring positions are positions i and i+3, i and i+4, i and i+7 or i or i+11 which indicates that the peptide must have sufficient length to possess at 12 amino acids. However, claim 6 depends from claim 1 and claim 1 merely recites a recombinant peptide, which is inclusive of peptides which only have 2 amino acids. While the peptides utilized in the instant specification would possess this many amino acids, limitations from the specification are not incorporated into the claims. Therefore, the scope of the encompassed peptide is unclear.
Claim 9 as currently written is vague and indefinite. MPEP 2173.05(h) recites alternative limitations. Examples are alternatives may be set forth as "a material selected from the group consisting of A, B, and C" or "wherein the material is A, B, or C". In claim 9, various groups utilize correct alternative language such as R1 is selected form Cl, Br, I or F. However, the recitation for A and L utilize “and” instead of “or” and therefore create uncertainty as to whether the listings are meant to be in the alternative or if all are required.
Claim 15 as currently written is vague and indefinite. The claim recites SEQ ID NO: 1 but the claim also recites: (AASLDELQAEIEQLEERNYALRKEIEDLQKQLEKLGAP, FosW). The sequence recited in the parentheses does not match the sequence for SEQ ID NO: 1 disclosed in the instant specification. Specifically, there is an additional A at the beginning of the sequence in the claim that is not present in the sequence of the specification. Therefore, the scope is unclear because it isn’t clear if the sequence in the parentheses are required or if the SEQ ID is represented by the sequence in the specification. The examiner notes that the claim is being interpreted as being directed to SEQ ID NO: 1 as represented in the sequence listing.
Claim 10 is included in the rejection as they depend on a rejected base claim and they do not clarify the issues.
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.
Claims 21-23 and 25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to laws of nature and a natural phenomenon without significantly more.
The claims recite laws of nature and natural phenomena. These judicial exceptions are not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception as explained below:
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP § 2106:
Step (1). Is the claim directed to a process, machine, manufacture, or composition of matter?
Step (2A). Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea?
Prong 1 – Does the claim recite a law of nature, natural phenomenon, or an
abstract idea?
Prong 2 – If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application?
Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP § 2106.05(a)
Applying the judicial exception with, or by use of, a particular machine. See MPEP § 2106.05(b)
Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP § 2106.05(c)
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. See MPEP § 2106.05(d)
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP § 2106.05(e)
Step (2B). If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step (2A), Prong 2, as well as two additional considerations:
Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis
Step (1): The answer to this step is yes since claims 21-23 are directed to a kit, aka a product, which is a statutory category.
Step (2A):
Product of Nature Definition
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979.
Claim Analysis
Prong 1
The markedly different characteristics analysis is part of Step 2A Prong One, because the courts use this analysis to identify product of nature exceptions.
Claim 21 recites a kit comprising i) a nucleic acid encoding a recombinant peptide wherein the recombinant peptide comprises at least two derivatisable amino acid residues located at anchoring position, each derivatisable amino acid comprising a reactive thiol group and ii) a crosslinker wherein the cross-linker is capable of reacting with said reactive thiol groups such that the cross-linker is capable of forming thioether crosslinks. The broadest reasonable interpretation of claim 21 is that it include any nucleic acid which encodes a peptide with at least two thiol groups, for example cysteine. The crosslinker is any crosslinker that forms a thioether.
Each part is analyzed and compared to its corresponding natural counterpart.
As indicated above part i) is any nucleic acid encoding any peptide that has at least two cysteines. As taught by Silverstein (The Plant Journal, 2007) multicellular organisms produce small cysteine-rich antimicrobial peptides. Table 1 shows various different cysteine-rich peptide classes in plants. Identification of plant CRPs from gene sequences are taught. This suggests nucleic acids encoding peptides that are cysteine rich occurs in nature. Nothing in the instant claim recitation for i) distinguishes the instantly claimed nucleic acid structurally from those found in nature.
Regarding part ii) Zhang et al. (J Biol Chem, 2013) teaches that IgG1 thioether bond formation is naturally occurring. Therefore, the recitation crosslinker which forms a thioether does not appear to distinguish the instant claims from the naturally occurring counterpart.
Therefore, claim 21 is clearly directed to a product by nature, particularly two naturally occurring products. Since the claim is directed to a kit, each natural product is present separately.
Regarding claims 22 and 25, while these crosslinkers are not found in nature. The nucleic acid, particular part i, is still not structurally or functionally different from those found in nature.
Regarding claim 23, this claim indicates the kit further comprises a cell. This also is a natural product. The claim is broad and encompasses any cell and any cell type. Thus, the claim fails to recite anything other than a naturally occurring product.
Therefore, the answer to step 2A prong 1 is yes.
Prong 2:
The Prong Two analysis considers the claim as a whole. That is, the limitations containing the judicial exception as well as the additional elements in the claim besides the judicial exception need to be evaluated together to determine whether the claim integrates the judicial exception into a practical application.
Here the claims are directed to a kit. The broadest reasonable interpretation is that each part, i.e. the nucleic acid, crosslinker and cell, are packaged separately. Therefore, there are no additional elements besides the judicial exception. While claim 23 recites crosslinkers which do not occur in nature, these crosslinkers are not interacting with the nucleic acid or cell such that change the function or structure of the nucleic acid and cell. But are in fact just present.
Therefore, the answer to step 2A prong 2 is No.
Step (2B):
There are no additional elements.
Therefore, the answer to step (2B) is No.
Conclusion
Claims 21-23 are directed to a judicial exception and do not qualify as eligible subject matter under 35 U.S.C. § 101.
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 of this title, 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 35 U.S.C. 103 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 6-12, 18 and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over Fairlie et al. (Peptide Science 2016, cited on PTO Form 1449) in view of Fasan et al. (WO2017223207, cited on PTO Form 1449).
Applicant Claims
The instant application claims a method of producing a conformationally constrained peptide in a cell, the method comprising: i) providing a cell containing a recombinant peptide, wherein the recombinant peptide comprises at least two derivatisable amino acid residues located at anchoring positions, each derivatisable amino acid comprising a reactive thiol group; ii) contacting the cell with a cross-linker, wherein the cross-linker is capable of reacting with said reactive thiol groups; and iii) culturing the cell in the presence of the cross-linker, such that the cross-linker forms thioether cross-links with the at least two derivatisable amino acids, thereby producing the conformationally constrained peptide in the cell.
The instant application claims a kit comprising: i) a nucleic acid encoding a recombinant peptide, wherein the recombinant peptide comprises at least two derivatisable amino acid residues located at anchoring positions, each derivatisable amino acid comprising a reactive thiol group; and ii) a cross-linker, wherein the cross-linker is capable of reacting with said reactive thiol groups, such that the cross-linker is capable of forming thioether cross-links with the at least two derivatisable amino acids.
The examiner notes that in every instance, the word optional/optionally, is interpreted as reciting elements that are not required to be present.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Fairlie et al. is directed to stapling peptides using cysteine crosslinking. When stapling peptides, chemists can chemically manipulate the peptide framework to mimic the binding site of proteins, to fine-tune its biological activity, to make it more stable to proteolytic degradation and/or to adjust its overall pharmacokinetic properties. Using this strategy a number of bioactive peptides have been generated for a range of biological applications including the targeting of intracellular protein-protein interactions (page 843, left column). Figure 1 shows conformation stabilization of α-helical and cyclic peptides by stapling together two cysteines with a suitable crosslinker. In recombinantly express peptides and proteins, cysteines can simply be engineered into the coding sequence (page 844, left column). The ultimate goal of peptide stapling is often the stabilization of a given bioactive conformation. To accomplish this, the cysteine pair must be included at positions that facilitate the macrocyclization of the peptide and ideally do not compromise target binding. For instance, in an α-helical peptide, residues located at the (i, i+4), (i, i+7) or (i, i+11) positions reside on the same face of the helix and are therefore strategic points to place two cysteines (Figure 1; page 844 right column). Figure 3B shows the a-helical stabilization of a peptide fragment with (i, i+4) connecting crosslinker.
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. With growing interest to create helical peptide inhibitors of therapeutically relevant intracellular PPIs (protein-protein interactions), novel sets of bis-electrophilic linkers have bene development with emphasis in improving not just the helical conformation of the peptide but also to enhance their cellular uptake and resistance toward proteolytic degradation (page 846, right column).
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Figure 10 shows the bicyclization of a tri-cysteine phage displayed peptide with a TBMB linker:
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Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Fairlie et al. teaches crosslinking of peptides with cysteine/thiols with the same crosslinkers as instantly claimed and suggests that in recombinantly express peptides and proteins, cysteines can simply be engineered into the coding sequence, Fairlie et al. does not teach producing a conformationally constrained peptide in a cell. However, this deficiency is cured by Fasan et al.
Fasan et al. is directed to cyclic peptide inhibitors of hedgehog proteins. Claimed and taught are cyclic peptides which include cysteine residues (paragraph 00122; claims). The cyclic peptide can include a crosslinker wherein the cyclic peptide forms:
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(paragraph 0024, 0026). Figure 18 shows a linear peptide in which two amino acid residues to be linked together are cysteine residues and the cyclization reaction is carried out using a bifunctional cysteine-reactive crosslinking agent (paragraph 0165). It is taught that while chemical synthesis is one method for preparing the inhibitors, selected cyclic peptides can be prepared also by recombinant methods. Upon expression of the precursor polypeptide in the cell (E. coli), the crosslinker reaches with a proximal cysteine residue resulting in the formation of side-chain-to-side-chain cyclic peptides (paragraph 00174; 00260). A specific crosslinker taught is M5-S9:
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(paragraph 00288).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Fairlie et al. and Fasan et al. and produce the conformationally constrained peptide in a cell. One skilled in the art would have been motivated produce the peptide in a cell as Fasan et al. teaches that constrained peptides can be produced either by chemical synthesis or via recombinant methods. In light of the teachings of Fasan et al. that either method can be utilized and Fairlie et al. teaches that peptides can be produced wherein the cysteines can simply be engineered into the coding sequence, there is a reasonable expectation of success in producing a conformationally constrained peptide in a cell.
Regarding claims 1-2, one skilled in the art would have been motivated to provide a cell containing the recombinant peptide as this is required for cyclization. Since both Fairlie et al. and Fasan et al. are concerned with forming conformationally constrained peptides, depending on the desired peptide which is to be utilized, one skilled in the art would utilize a nucleic acid which encodes the desired peptide sequence with the cell, contact the cell with the crosslinker and then culture the cells in order to produce the peptide which is then present to react with the crosslinker to form the conformationally constrained peptide in a cell.
Regarding claim 6, Fairlie et al. teaches in an a-helical peptide, residues located at the (i, i+4), (i, i+7) or (i, i+11) positions reside on the same face of the helix and are therefore strategic points to place two cysteines and exemplifies sequences with cysteines at these positions.
Regarding claim 7-8, the sequences shown with the crosslinking in Fairlie et al. (see Fig.3B, 4 and 10) only contain cysteines at the anchoring positions (aka the crosslinking cysteines).
Regarding claims 9-12, 22, 24, and 25, Fairlie et al. teach the following crosslinkers:
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wherein R1 is Br, n is 1 or 2, m is 1 or 0, A is C6 alkenylene/arylene, Y is a C1 alkylene and L is a covalent bond. The first structure reads on formula 2aa of claim 12. The first structure corresponds to the second structure in the first line; the second structure corresponds to the second structure in the second line; the third structure corresponds to the third structure in the second line of claims 24-25.
Regarding claim 18 and 23, Fasan et al. teaches E. coli
Regarding claim 20, as taught in Fasan et al., the peptide was produced by recombinant methods in E. Coli in the presence of the crosslinker. Purification and isolation of the peptide is taught (paragraph 0260).
Regarding claim 21, Fasan et al. teaches kits or packages wherein the agents may be packaged separately or together. The kit includes instructions (paragraph 00218). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Fairlie et al. and Fasan et al. and utilize a kit and packaged within the kit are the nucleic acid for encoding the peptide, the crosslinker and cells. Since Fasan et al. teaches that the constrained peptide can be made by recombinant methods and suggest kits for the respective agents, one skilled in the art would have been motivated to package separately each component for shipping and storage as suggested by Fasan et al.
Claims 3-4 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Fairlie et al. in view of Fasan et al. as applied to claims 1-2, 6-12, 18 and 20-25 above and in further view of Worrall (the FEBS Journal, 2010) and Brent et al. (EP1405911).
Applicant Claims
Regarding claims 3-4, these claims are merely interpreted as requiring assaying to determine if the conformationally constrained peptide is able to inhibit association between the first and second candidate binding partner. The broadest reasonable interpretation of the claims is that the conformationally constrained peptide includes both those which can inhibit and those which do not inhibit as neither claim requires a particular effect just that the ability to inhibit is determined. In light of this interpretation the recitation of first and second candidate binding partner is interpreted as being any known binding partners.
The instant application claims the recombinant peptide is derived from the FosW peptide having the amino acid sequence set forth in SEQ ID NO: 1 modified to comprise at least two derivatizable amino acids located at anchoring positions in the FosW peptide.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Fairlie et al. and Fasan et al. are set forth above. Fairlie et al. teaches crosslinking of peptides with cysteine/thiols with the same crosslinkers as instantly claimed and suggests that in recombinantly express peptides and proteins, cysteines can simply be engineered into the coding sequence. Fairlie et al. teaches in an a-helical peptide, residues located at the (i, i+4), (i, i+7) or (i, i+11) positions reside on the same face of the helix and are therefore strategic points to place two cysteines and exemplifies sequences with cysteines at these positions. Fasan et al. teaches formation of the conformationally constrained peptide can be via recombinant methods in a cell.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Fairlie et al. suggests crosslinking between cysteine residences of peptide chains, Fairlie et al. does not expressly teach the amino acid sequence set forth in SEQ ID NO: 1 which is modified to include two cysteines at anchoring positions or assaying the ability of the peptide to inhibition association between the first and second binding partner. However, these deficiencies are cured by Worrall et al. and Brent et al.
Worrall et al. is directed to the thermodynamic analysis of Jun-Fos coiled coil peptide antagonists. It is taught that the transcriptional regulator activator protein-1 (AP-1) generally consist of heterodimers of Jun and Fos families if proteins (page 663, introduction). AP-1 upregulation is involved in a number of diseases. Thus, peptides capable of specifically sequestering key components of AP-1 and prevent its function show great promise as the starting point for drugs to combat a number of diseases (page 664, left column). Developing rules that can assist in the discovery of new binding partners for coiled-coil-containing proteins therefore has great potential for influencing biology by elucidating stable and specific protein-protein interactions. Several peptides, based upon the coiled coil regions of AP-1 that are able to bind and prevent them from binding to DNA were derived (page 664, right column). Table 1 shows these peptide sequence wherein one specifically taught is FosW (table 1). As shown below SEQ ID NO: 1 of the instant claims (Qy) has 100% identity to the FosW of Worrall et al.(Db).
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Brent et al. is directed to an interaction trap system for detecting protein interaction. The invention features a method of determining whether a first protein is capable of physically interacting with a second protein. The method includes (a) providing a host cell which contains (i) a reporter gene operably linked to a DNA-binding-protein recognition site; (ii) a first fusion gene which expresses a first fusion protein, the first fusion protein comprising the first protein covalently bonded to a binding moiety which is capable of specifically binding to the DNA-binding-protein recognition site; and (iii) a second fusion gene which expresses a second fusion protein, the second fusion protein including the second protein covalently bonded to a gene activating moiety and being conformationally-constrained; and (b) measuring expression of the reporter gene as a measure of an interaction between the first and said second proteins (paragraph 0003). The second protein is a short peptide of at least 6 amino acids in length and less than or equal to 60 amino acids in length. Constraining by disulfide bonds between cysteine residues is taught (paragraph 0004). Taught is the formation of peptide libraries in E. coli. The library contained 2.9 x 109 members, of which more than 109 directs the synthesis of peptides. (paragraph 0088). To screen for interacting peptides, the library is used to transform the yeast train. Transformants are obtained and pooled (paragraph 0089). The strength of binding is judged according to the intensity of the blue color formed by a colony of the yeas that contains each different interactor (paragraph 0090). The system may also be used to identify agonists or antagonists, simply by adding to a known pair of interacting proteins, a candidate agonist or antagonist interactor and assaying for an increase or decrease (respectively) in reporter gene expression, as compared to a control reaction lacking the candidate compound or protein. From pools demonstrating a positive result, the particular interacting protein or agonist or antagonist is then identified by individually assaying the components of the pool (paragraph 0111).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings Fairlie et al., Fasan et al. Worrall et al. and Brent et al. and utilize a peptide library of conformationally contained peptides to find peptides which antagonize the interaction between Jun and Fos in order find antagonists of AP-1 upregulation. Worrall et al. teaches that upregulation of AP-1 causes a variety of different diseases. Brent et al. teaches a system which can be used to detect protein interactions including identify agonist or antagonists of particular interacting proteins. Therefore, when desiring to find antagonists of AP-1, one skilled in the art would have been motivated to add first and second candidate binding partners in combination with candidate peptides and assaying whether the compounds bind and inhibit. Since Fairlie et al. and Brent et al. both teach the use of conformationally constrained to study protein-protein interactions there is a reasonable expectation of success. This renders obvious instant claims 3-4.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings Fairlie et al., Fasan et al. Worrall et al. and Brent et al. and utilize a cysteine modified FosW peptide. One skilled in the art would have been motivated to utilize a cysteine modified FosW peptide when studying Jun and Fos interactions and their ability to antagonize AP-1. One skilled in the art would have been motivated to utilize FosW as it taught as peptide sequence which can antagonize AP-1. One skilled in the art would have been motivated to conformationally constrain the FosW peptide in order to improve not just the helical conformation of the peptide but also to enhance the cellular uptake and resistance toward proteolytic degradation as taught by Fairlie et al. Since Fairlie et al. teaches that recombinantly express peptides and proteins, cysteines can simply be engineered into the coding sequence. One skilled in the art would have been motivated to utilize two cysteines as residues located at the (i, i+4), (i, i+7) or (i, i+11) positions reside on the same face of the helix and are therefore strategic points to place two cysteines was taught by Fairlie et al. Rendering obvious claim 15.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Fairlie et al. in view of Fasan et al. as applied to claims 1-2, 6-12, 18 and 20-25 above and in further view of Timmerman et al. (ChemBioChem, 2005, cited on PTO Form 1449).
Applicant Claims
The instant application claims wherein the concentration of the cross-linker is between 1 µM and 1 mM, optionally between 10 µM and 100 µM, and/or wherein the cell is cultured in the presence of the cross-linker for a period of at least 20 minutes.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Fairlie et al. and Fasan et al. are set forth above.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Fairlie et al. does not expressly teach concentration or time for the crosslinking. However, this deficiency is cured by Timmerman et al.
Timmerman et al. is directed to rapid and quantitative cyclization of multiple peptide loops onto synthetic scaffolds for structural mimicry of protein surfaces. In aqueous solution reaction between dibromoxylenes T2 is fast and selective for cysteines. Taught is a 0.5 mM solution of the peptide and 1.05 equivalent of m-T2 gives the monocyclic product 2a in less than 15 min at RT (see table 1).
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Scheme 1.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Fairlie et al., Fasan et al. and Timmerman et al. and manipulate the concentration and time for reaction. As taught by Timmerman et al. in aqueous solutions the reaction is fast. One skilled in the art would have been motivated to monitor reaction times and determine the optimal reaction times to achieve the highest yield of the constrained peptide.
The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results. The amount crosslinker is a parameter that a person of ordinary skill in the art would routinely optimize based on the concentration of the peptides present. It would have been obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). NOTE: MPEP 2144.05.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Kaake et al. (Molecular & Cellular Proteomics, 2014) discusses in vivo crosslinking to define protein-protein interactions in living cells.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636