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 without traverse of Group I (i.e., claims 1-6 and 97 drawn to an engineered peptide comprising a p110beta targeting peptide and a delivery moiety that is coupled to the p110beta targeting peptide) in the reply filed on December 18, 2025, is acknowledged. Additionally, Applicant’s election without traverse of Species A (i.e., a single and specific engineered peptide as SEQ ID NO: 3 as a single and specific p110beta targeting peptide and SEQ ID NO: 6 as a single and specific delivery moiety where the engineered peptide does not include any ester-linked groups) in the reply filed on December 18, 2025, is acknowledged.
Please note that Species A is expanded to include where the cell penetrating peptide can be SEQ ID NO: 4 in light of the Examiner’s search.
Status of Claims
Claims 1-87 were originally filed on April 4, 2023.
The amendment received on October 17, 2023, canceled claims 7-87; and added claims 88-101.
Claims 1-6 and 88-101 are currently pending and claims 1-5 and 97 are under consideration as claims 88-96 and 98-101 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claim 6 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 18, 2025.
Priority
The present application claims status as a 371 (National Stage) of PCT/US2021/054331 filed October 9, 2021, and claims priority under 119(e) to U.S. Provisional Application Nos. 63/090,121 filed on October 9, 2020, and 63/090,140 filed on October 9, 2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on April 4, 2023; November 17, 2023; and November 17, 2023, are being considered by the examiner.
Sequence Interpretation
For claim 3, please note that the Examiner is interpreting the scope as open-ended requiring 95-100% identity to SEQ ID NO: 3 with any N- and/or C-terminal additions.
For claim 5, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 4 or 6 with any N- and/or C-terminal additions.
Specification
The disclosure is objected to because of the following informalities: the specification describes Figures 10A-10H, 37A-37D, and 51A-51I, reference color in the figures. However, the figures have not been filed in color. Appropriate correction is required.
The disclosure is objected to because of the following informalities: [0111], discusses an amino acid sequence without an accompanying SEQ ID NO. Pursuant to MPEP 2422 and 37 CFR 1.821(a), any amino acid sequence at least 4 defined amino acids in length requires a sequence identifier. Appropriate correction is required.
The disclosure is objected to because of the following informalities: the paragraph numbering is not provided consecutively. In particular, it is noted that on page 58, the paragraph numbering goes from [0233] to [0001]. It is respectfully requested that the paragraph numbering is redone in order to provide the numbering consecutively in ascending order. Appropriate correction is required.
Claim Objections
Claim 97 is objected to because of the following informalities: claim 97 recites, “[a] kit comprising: (a)….; (b)….; (c)….; (d)….; (e)….” It is respectfully requested that claim 97 recites, “[a] kit comprising: (a)….; (b)….; (c)….; (d)….; and/or (e)….” in order to be grammatically correct. Please note that alternative language can also be utilized, e.g., “or”, “and”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5 and 97 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 includes a “peptide” where the structure of the peptide is not limited thereby encompassing peptides of any structure and/or amino acid sequence. Rather, the scope of claim 1 attempts to limit the peptide via function; more specifically, the peptide is to target p110beta. Moreover, dependent claim 2 further limits the peptide’s function by requiring the peptide to be capable of selectively binding p110beta or a complex thereof and/or selectively inhibiting p110beta activity. Thus, the scope of claims 1-2, 4-5, and 97 encompass a peptide with any structure and/or amino acid sequence as long as the peptide exhibits the functions of targeting p110beta, and being capable of selectively binding p110beta or a complex thereof and/or selectively inhibiting p110beta activity. However, there is no core structure and/or sequence that is necessary for the peptide to exhibit the aforementioned claimed functions.
Furthermore, dependent claim 3 includes a “homologue” or “variant” of SEQ ID NO: 3 (i.e., TKKSTKTINPSKYQTIRK) where the homologue and/or variant must exhibit the function of SEQ ID NO: 3. The function referred to is targeting p110beta. It is noted that the instant specification defines a “variant” as referring to a polypeptide that differs from a reference polypeptide, but retains essential and/or characteristic properties (structural and/or functional) of the reference polypeptide (See instant, [0159]). As such, a homologue or variant of SEQ ID NO: 3 is not limited structurally thereby encompassing any structures and/or amino acid sequences. Rather, the scope of claim 3 attempts to limit the homologue/variant’s function by requiring the homologue/variant to retain the function of targeting p110beta. However, there is no core structure and/or sequence that is necessary for the homologue/variant to target p110beta.
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, Hirsch et al. US Patent No. 8,105,796 B2 teaches that p110beta represents an isoform of one of the two components of a phoshoinositide 3-kinase (PI3K) heterodimer (See Hirsch, col. 1, 4th paragraph). The p110 component represents the catalytic domain of the enzyme (See Hirsch, col. 1, 4th paragraph). Class I PI3Ks encompass four different isoforms; namely, alpha, beta, gamma and delta (See Hirsch, col. 1, 4th paragraph). PI3Kbeta (i.e., p110beta) is a class 1A member that is ubiquitously expressed and posses the unique feature of being activated not only by tyrosine kinase receptors, but also by G protein-coupled receptors (See Hirsch, col. 1, 4th paragraph). Hirsch et al. further teaches a PI3Kbeta protein with a single substitution of K805R, which renders the protein catalytically inactive (See Hirsch, col. 4, 6th paragraph). As such, Hirsch et al. demonstrates that even a single conservative substitution alters the function of the protein. Thus, the claims are directed to peptides and homologues/variants of SEQ ID NO: 3 with a certain function but no correlated structure associated with that function. Without such structure, the specification does not convey possession of the breadth of the claimed genera.
Alternatively, the written description requirement may be met by provided a representative number of species of the genus. In this, the specification does not provide an example of a peptide sequence other than SEQ ID NO: 3, and provides limited examples of a homologue/variant of SEQ ID NO: 3. The specification teaches that a variant of SEQ ID NO: 3 can differ by one or more modifications at the sequence level or post-translational modifications thereby including substitutions, additions, deletions, methylation, glycosylations, etc. (See instant, [0158]). As such, a variant of SEQ ID NO: 3 encompasses one or more modifications including where every residue is substituted. Example 1 teaches that p110 activity is tightly controlled by regulatory subunits where one regulatory subunit, p85, binds to one p110 to form a complex (See instant, pg. 102, 2nd paragraph). P110 proteins consist of four domains: p85-binding domain (PHD), ras-binding domain (RBD), C2 domain, and helical/kinase domain (HKD) (See instant, pg. 102, 2nd paragraph). Only C2 domains showed a discrete consensus when the sequences of the four p110 isoforms were aligned (See instant, pg. 102, 2nd paragraph). Other p110 domains such as PHD, RBD, and HKD were highly homologous (See instant, pg. 102, 2nd paragraph). Plus, the instant specification demonstrates that SEQ ID NO: 3 in p110beta was not found in other p110s, and this motif is important for p110beta activation (See instant, pg. 102, 2nd paragraph). Moreover, the instant specification teaches that deletion of all of SEQ ID NO: 3 can destabilize the p110beta/p85 complex, deletion of lysine or arginine at both ends of SEQ ID NO: 3 can disassemble the p110beta/p85 complex, and deletion of non-charged residues will not affect p110beta’s function (See instant, pg. 108, 2nd paragraph). However, the specification does not provide any data demonstrating these assertions. Moreover, even if data is provided, such limited examples would not constitute a representative number of species given the breadth of the claimed genera. Thus, the teachings in the specification are not sufficient for the skilled artisan to envisage what peptides will target p110beta and be capable of selectively binding p110beta or a complex thereof and/or selectively inhibiting p110beta activity, which homologues or variants of SEQ ID NO: 3 will target p110beta.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, what is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides which preserve the required function, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, claims 1-5 and 97 do not meet the written description requirement.
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 1-3 and 97 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hirsch et al. US Patent No. 8,105,796 B2 issued on January 31, 2012, alone or as evidenced by Sjodin et al., Israel J. Chem. 63:e202300070 (2023) and/or Namiki et al., Biochem. Biophys. Res. Commun. 305:592-597 (2003).
For claims 1 and 3, regarding an engineered peptide comprising the p110beta targeting peptide component, Hirsch et al. discloses a purified PI3Kβ protein comprising a gluthionine-S-transferase (GST) protein where the PI3Kβ protein comprises an amino acid sequence of SEQ ID NOs: 3 or 4 (See Hirsch, col. 11, 2nd paragraph) thereby constituting an engineered fusion peptide given that SEQ ID NOs: 3 or 4 could only be fused to a GST protein via recombinant engineering. When comparing instant SEQ ID NO: 3 with Hirsch’s SEQ ID NO: 4, there is 100% identity with residues 413-430 of Hirsch’s SEQ ID NO: 4. As discussed in the “Sequence Interpretation” section supra, the peptide comprising instant SEQ ID NO: 3 encompasses any N- and/or C-terminal additions. As such, Hirsch’s SEQ ID NO: 4 is encompassed as a p110beta targeting peptide as recited in instant claims 1 and 3.
Furthermore, regarding the peptide being a p110beta targeting peptide, since Hirsch et al. teaches a peptide comprising 100% identity to instant SEQ ID NO: 3 thereby satisfying the structural limitations of the claimed peptide, it would then necessarily follow that Hirsch’s SEQ ID NO: 4 exhibits the function of targeting p110beta. Pursuant to MPEP 2112.01(II), “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
Additionally and/or alternatively, since Hirsch et al. discloses a p110beta targeting peptide thereby constituting a well-known sequence, the functional property (i.e., targeting p110beta) of the peptide as claimed and the known peptide are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new functional property (i.e., targeting p110beta) which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977).
Regarding a delivery moiety that is coupled to the p110beta targeting peptide, as discussed supra, Hirsch’s SEQ ID NO: 3 or 4 as a p110beta targeting peptide comprises a GST protein thereby constituting where the GST protein is coupled to the p110beta targeting peptide.
Moreover, as evidenced by Sjodin et al., GST proteins undergo cellular uptake and thereby deliver pharmaceutical cargo to intracellular sites (See Sjodin, abstract). Additionally and/or alternatively, Namiki et al. found that the fluorescent-dye-labeled GST from Schistosoma japonicum was delivered into COS7 cells (See Namiki, abstract). The intracellular transduction of GST was also observed in HeLa, NIH3T3, and PC12 cells as well as in hippocampal primary neurons, indicating that a wide range of cell types is permissive for GST transduction (See Namiki, abstract). Namiki et al. concluded that GST is a novel protein transduction domain (PTD) which may be useful in the intracellular delivery of biologically active molecules such as small molecule drugs, bioactive peptides or proteins (See Namiki, abstract). Thus, Namiki et al. suggests that a GST protein functions as a delivery moiety. Pursuant to MPEP 2112.01(II), “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. Thus, the teachings of Hirsch et al. satisfy the claim limitations with respect to an engineered peptide comprising a p110beta targeting peptide comprising an amino acid sequence that is 100% identical to instant SEQ ID NO: 3 and a delivery moiety that is coupled to the p110beta targeting peptide as recited in instant claims 1 and 3.
For claim 2, since Hirsch et al. teaches a peptide comprising 100% identity to instant SEQ ID NO: 3 thereby satisfying the structural limitations of the claimed peptide, it would then necessarily follow that Hirsch’s SEQ ID NO: 4 exhibits the function being capable of selectively binding p110beta or a complex thereof, and/or selectively inhibiting p110beta activity. Pursuant to MPEP 2112.01(II), “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
Additionally and/or alternatively, since Hirsch et al. discloses a p110beta targeting peptide thereby constituting a well-known sequence, the functional properties (i.e., being capable of selectively binding p110beta or a complex thereof, and/or selectively inhibiting p110beta activity) of the peptide as claimed and the known peptide are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of new functional properties (i.e., being capable of selectively binding p110beta or a complex thereof, and/or selectively inhibiting p110beta activity) which are inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Thus, the disclosure of Hirsch satisfies the claim limitations as recited in instant claim 2.
For claim 97, it is noted that the broadest reasonable interpretation of the scope of claim 97 encompasses where the kit can comprise one or more of options (a)-(e). As such, the scope of claim 97 encompasses a kit comprising the engineered peptide of claim 1.
As discussed supra for claim 1, Hirsch et al. discloses a purified PI3Kβ protein comprising a gluthionine-S-transferase (GST) protein where the PI3Kβ protein comprises an amino acid sequence of SEQ ID NOs: 3 or 4 (See Hirsch, col. 11, 2nd paragraph). This fusion protein is absorbed onto gluthionine-derivatized wells of 96-well microtiter plates and are contacted with test compounds from a small molecule library at pH 7.0 in a physiological buffer solution (See Hirsch, col. 11, 2nd paragraph). The fusion peptide being absorbed onto wells of a microtiter plate would constitute a kit (i.e., a component that is used to package, sell, market, deliver and/or administer the engineered peptide of claim 1) (See instant, pg. 91, 1st paragraph defining a “kit of parts”). Although, the scope of claim 97 does not expressly recite a “kit of parts”, a microtiter plate constitutes a means to package, sell, market, deliver and/or administer the engineered peptide of claim 1. Thus, the disclosure of Hirsch et al. satisfies the claim limitations as recited in instant claim 97.
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 and 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Hirsch et al. US Patent No. 8,105,796 B2 issued on January 31, 2012, alone or as evidenced by, Sjodin et al., Israel J. Chem. 63:e202300070 (2023) and/or Namiki et al., Biochem. Biophys. Res. Commun. 305:592-597 (2003), as applied to claim 1 above, and further in view of Streiker et al. US Publication No. 2015/0297742 A1 published on October 22, 2015, alone or as evidenced by, Derossi et al., J. Biol. Chem. 30:18188-18193 (1996), and Guo et al., Biomedical Rep. 4:528-534 (2016), as applied to claims 4-5 herewith.
For claims 4-5, as discussed supra, Hirsch et al. teaches a purified PI3Kβ protein comprising a gluthionine-S-transferase (GST) protein where the PI3Kβ protein comprises an amino acid sequence of SEQ ID NOs: 3 or 4 (See Hirsch, col. 11, 2nd paragraph). As such, Hirsch et al. teaches a fusion comprising a p110beta targeting peptide and a protein transduction domain as a delivery moiety. However, Hirsch et al. does not expressly teach that the delivery moiety is a cell penetrating peptide such as instant SEQ ID NO: 6.
Streiker et al. teaches a conjugate comprising a biological or clinically active or therapeutic protein such as an enzyme and one or several multivalent cell-penetrating peptide(s) where each multivalent CPP(s) comprise at least two CPPs and where the multivalent CPP(s) is/are covalently attached (i.e., same as coupled) to the protein (See Streiker, [0008], [0017]-[0019], [0085], [0093]). Streiker et al. defines a CPP as referring to short peptides of 5 to 40 amino acids in length that facilitate cellular uptake of various cargoes such as small chemical molecules to nucleic acids, peptides, proteins, drugs, etc. (See Streiker, [0050]). The attachment of one or more multiple CPPs to the cargo facilitates the delivery of the cargo into cells (See Streiker, [0050]). Streiker et al. also teaches that preferably, a CPP is a carrier peptide capable of being internalized into a cell (Streiker, [0058]-[0060]). As evidenced by Guo et al., CPPs are also known as protein transduction domains (See Guo article, abstract). As such, Streiker’s CPPs also constitute protein transduction domains.
The CPP(s) comprise or consist of the amino acid sequence selected from SEQ ID NOs: 1 to 760 (See Streiker, [0067]). Preferably, the CPP(s) comprise or consist of SEQ ID NOs: 1-8 where SEQ ID NO: 1 is penetratin (i.e., RQIKIWFQNRRMKWKK), and/or SEQ ID NO: 4 is RRRRRRRRR (i.e., R9) (See Streiker, [0069]-[0079]; Table 1). When comparing Streiker’s SEQ ID NO: 4 with instant SEQ ID NO: 4 there is 100% identity with the Streiker SEQ ID NO: 4 having an additional arginine residue, but as discussed in the “Sequence Interpretation” section supra, the scope of the CPP amino acid sequence of instant claim 5 encompasses any N- and/or C-terminal additions. As such, Streiker’s SEQ ID NO: 4 constitutes a CPP having a sequence identical to instant SEQ ID NO: 4 as recited in instant claims 4-5. Furthermore, Table 1 depicts all 760 CPP amino acid sequences taught by Streiker including SEQ ID NO: 104 (i.e., RQPKIWFPNRRKPWKK) (See Streiker, Table 1). As evidenced by Derossi et al., Streiker’s SEQ ID NO: 104 is an analog/variant of the penetratin amino acid sequence of Streiker’s SEQ ID NO: 1 (See Derossi, pg. 18189, Figure 1). When comparing Streiker’s SEQ ID NO: 104 with instant SEQ ID NO: 6, there is 100% identity. As such, since Streiker et al. expressly teaches where CPP comprises penetratin (SEQ ID NO: 1) and/or R9 (SEQ ID NO: 4) (See Streiker, [0079]), selecting a penetratin analog/variant with or without R9 as the CPP would be obvious as further articulated below. Moreover, given that the GST protein taught by Hirsch et al. functions as a protein transduction domain (See discussion in the 102 rejection supra) thereby constituting a delivery moiety, and CPPs such as Streiker’s SEQ ID NOs: 4 and 104 function as protein transduction domains thereby constituting delivery moieties, an ordinary skilled artisan would be motivated with a reasonable expectation of success to substitute Hirsch’s GST protein with Streiker’s SEQ ID NO: 4 and/or 104.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the teachings of Hirsch et al. and substitute instant SEQ ID NO: 4 and/or 6 in lieu of the GST protein of a fusion peptide comprising a purified PI3Kβ protein containing instant SEQ ID NO: 3 as a p110beta targeting peptide and a GST protein in order to deliver the purified PI3Kβ protein into cells. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because one or more CPPs such as instant SEQ ID NO: 4 and/or 6 were known to be covalently coupled a biological or clinically active or therapeutic protein such as an enzyme as taught by Streiker 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 peptide of Hirsch et al. comprised a purified PI3Kβ protein containing instant SEQ ID NO: 3 as a p110beta targeting peptide and a GST protein where the GST protein functions as a protein transduction domain by delivering cargo into cells, and therefore, substituting instant SEQ ID NO: 4 and/or 6 in lieu of the GST protein would support the delivery of the purified PI3Kβ protein into cells by constituting the simple substitution of one known element for another to obtain predictable results and/or 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 under 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 before the effective filing date of the instant application, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654