DETAILED ACTION
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
The instant application is a national stage entry of PCT/US2022/081357 (filed on 12/12/2022), which claims priority benefit of U.S. Provisional Application No. 63/289399 (filed on 12/14/2021) under 35 U.S.C. 119(e).
Information Disclosure Statement
The four information disclosure statements (IDSs) submitted on 6/11/2024, 3/20/2025, and 5/15/2025 are in compliance with the provisions of 37 C.F.R. 1.97. Accordingly, all references cited in these IDSs have been fully considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
i) the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
i) the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is incomplete because it does not state the size of the ASCII text file in bytes. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claim 5 is objected to since an abbreviation (“HIV-TAT”) is used without providing the full form. Any abbreviation should be defined when first recited in a set of claims by spelling out the full term followed by the abbreviation in parentheses. Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 1-3, 6-10, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Pub. No. CN 110982802 A; English translation) in view of Aoyama et al. (Circulation 2005, Vol. 111, pages 1652-1659; IDS cited).
Wang et al. discloses a recombinant human SGK3 protein kinase hydrogel, as well as methods of preparing and using it to promote myocardial regeneration (first par., page 1).
The recombinant human SGK3 protein kinase is a fusion protein comprising SGK3 protein kinase and a transmembrane peptide. To form it, Wang et al. teaches connecting a SGK3 protein kinase sequence and a membrane-penetrating peptide sequence via a connecting peptide. The formed recombinant human SGK3 protein kinase is then mixed with a gelling precursor prepolymer solution to produce a hydrogel that can be administered (Abstract, page 1).
The SGK3 protein kinase preferably has amino acid sequence of SEQ ID NO: 1, while the transmembrane peptide is selected from any one of TAT, MPG, MPG∆NLS, stearyl-R8, Transportan, and Pep-1 (last two par., page 2). In a further preferred embodiment, the recombinant human SGK3 protein kinase has an amino acid sequence of SEQ ID NO: 2 (first par., page 3).
Wang et al. is comparable to the instant application’s fusion peptide as explained below:
Regarding claim 1: the disclosed fusion protein comprising SGK3 protein kinase is analogous to “A fusion peptide comprising a peptide fragment of Serum/Glucocorticoid Regulated Kinase 1 (SGK1)”.
The transmembrane peptide comprising a membrane-penetrating peptide sequence selected from a group that includes TAT meets “an internalization sequence”.
The preferred embodiment of SGK3 protein kinase having an amino acid sequence corresponding to SEQ ID NO:2, which comprises 10 consecutive amino acids (a.a. # 239-248) and 12 consecutive amino acids (a.a. # 262-273) of applicant’s SEQ ID NO: 1, as well as shares 86.6% identity to applicant’s SEQ ID NO: 1 (see sequence-to-sequence alignment below), satisfies the limitation “wherein the peptide fragment comprises at least 10 consecutive amino acids of SEQ ID NO:1, or a variant thereof having at least 85% sequence identity to SEQ ID NO:1”.
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Although the protein kinase disclosed by Wang et al. is SGK3 and not SGK1 as recited in the claim, it is known in the art that these two enzymes are two of the three isoforms that make up the SGK family of serine/threonine kinases as substantiated by Aoyama et al.. Aoyama et al. states that SGK2 and SGK3 were identified as isoforms of SGK1, with both SGK1 and SGK3 being broadly expressed including in the heart (first par. in right col., page 1652). Aoyama et al. shows that SGK1 is necessary to protect cardiomyocytes from apoptosis and contributes to the cardioprotective effects of IGF-I (first par. in right col., page 1654). In addition, experimental results demonstrate that SGK1 acts to modulate cardiomyocyte survival and hypertrophic response (Figure 6 and first par. in left col., page 1658). Since SGK1 regulates the survival and growth of cardiomyocytes and provides cardioprotection (Abstract, page 1652), a person with ordinary skill in the art before the effective filing date of the claimed invention would have replaced the SGK3 with SGK1 in Wang et al.’s fusion protein. It can be expected that such substitution would produce a protein kinase hydrogel that can be utilized to promote myocardial regeneration by reducing cell death and increasing proliferation of cardiomyocytes. Obviousness is based on the rationale that substitution of one known element for another known element, both elements having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See MPEP § 2143 and KSR International Co. v. Teleflex Inc. 550 US 398, 82 USPQ2d 1385 (2007).
Hence, claim 1 is obvious over Wang et al. in view of Aoyama et al..
Regarding claim 2: it can be predicted that replacing the SGK3 with SGK1 in the disclosed fusion protein would result in a modified recombinant protein kinase comprising the amino acid sequence of applicant’s SEQ ID NO:1, thereby fulfilling “wherein the peptide fragment of SGK1 comprises the amino acid sequence SEQ ID NO:1”.
Regarding claim 3: the modified recombinant protein kinase comprising SGK1 and transmembrane peptide is the same as “wherein fusion peptide consists essentially of the amino acid sequence SEQ ID NO:1 and an internalization sequence”.
Regarding claims 6-7: the modified recombinant protein kinase comprising SGK1 and transmembrane peptide necessarily has an amino acid sequence that “comprises (or “consist essentially of”) the amino acid sequence of SEQ ID NO:20”, which has 48 amino acids having TAT linked to a 35 amino acid residue of SGK1.
Regarding claim 8: the transmembrane peptide comprises a connecting peptide that links the SGK1 to the membrane-penetrating peptide sequence, which corresponds to “further comprising a linker between the peptide fragment of SGK1 and the internalization sequence”.
Regarding claims 9-10: administering the hydrogel comprising the modified recombinant protein kinase via injection into a subject’s coronary artery or heart muscle (eighth par., page 3; eighth par., page 8) is equivalent to “administering to the subject an agent that blocks the binding of endogenous SGK1 to endogenous glucocorticoid-induced leucine zipper (GILZ)”.
Performing the disclosed method of use to promote regeneration of myocardial cells, inhibition of heart remodeling, and improvement of cardiac function as therapy after myocardial infarction (first par., page 4; first par., page 9) is considered to meet the claimed method’s intended function of “treating a disease associated with aberrant Serum/Glucocorticoid Regulated Kinase 1 (SGK1) activity in a subject” given that aberrant or excessive SGK1 signaling is found in circulating endothelial cells in coronary heart disease and contributes to endothelial cell death in coronary vasculature.
Even though neither Wang et al. nor Aoyama et al. explicitly teaches that the fusion protein blocks the binding of endogenous SGK1 to endogenous GILZ, this is a property inherent to the modified fusion protein comprising SGK1 fused to an internalization sequence that does not need to be recognized at the relevant time. See MPEP § 2112. It should be noted that claim 10 further defines the agent being administered as “a fusion peptide comprising a peptide fragment of Serum/Glucocorticoid Regulated Kinase 1 (SGK1) and an internalization sequence, wherein the peptide fragment comprises at least 10 consecutive amino acids of SEQ ID NO:1, or a variant thereof having at least 85% sequence identity to SEQ ID NO:1”, indicating that said limitation is a mechanism of action that is an inherent property of the recited fusion peptide.
Regarding claim 14: treating myocardial infarction would provide protection from muscle cell death and consequently help treat heart failure, thereby satisfying the additional requirement that the disease is “a heart failure”.
Claims 1-3, 5-10, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Pub. No. CN 110982802 A; English translation) in view of Aoyama et al. (Circulation 2005, Vol. 111, pages 1652-1659; IDS cited) and Brooks et al. (Advanced Drug Delivery Reviews 2005, Vol. 57, pages 559-577).
The teachings of Wang et al. and Aoyama et al. are set forth above and applied herein. Wang et al. and Aoyama et al. are found to render claims 1-3, 6-10, and 14 obvious.
The modified fusion protein is similar to the following claims:
Regarding claim 5: the internalization sequence in claim 1 is further required to comprise “a HIV-TAT internalization domain”.
Wang et al. only teaches having TAT as the membrane-penetrating peptide sequence.
Nonetheless, Brooks et al. teaches that HIV-TAT peptide is another peptide known to possess cell penetrating properties. Due to the 9 amino acid stretch of basic amino acids (RKKRRQRRR), it is able to cross the plasma membrane of cells and deliver proteins, peptides, and nucleic acids (Abstract, page 559; section 6, page 572). One with ordinary skill in the art before the effective filing date of the claimed invention would have used HIV-TAT peptide instead of TAT as the membrane-penetrating peptide in Wang et al. and Aoyama et al.’s modified fusion protein with reasonable expectation that it would still facilitate the entry and delivery of SGK1 into cells like cardiomyocytes. Simple substitution of one known element for another to obtain predictable results.
Claim 5 is therefore obvious over Wang et al. in view of Aoyama et al. and Brooks et al..
Claims 1-3, 6-10, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Pub. No. CN 110982802 A; English translation) in view of Aoyama et al. (Circulation 2005, Vol. 111, pages 1652-1659; IDS cited) and Ghani (Molecular Biology Reports 2022 [e-publication: October 2021], Vol. 49, pages 675-685).
Wang et al. and Aoyama et al.’s teachings are described previously and applied herein. These prior art are found to render claims 1-3, 6-10, and 14 obvious.
Use of the modified fusion protein is comparable to the claims below:
Regarding claims 12-13: the disease is limited to “cancer” and further specified to be “a prostate cancer, colorectal carcinoma, glioblastoma, breast cancer, or endometrial cancer”, respectively.
Wang et al. and Aoyama et al. do not teach that the fusion protein is applicable for treatment of cancer.
Several studies, however, have implicated the role of SGK1 in cancer. For example, Ghani states that SGK1 regulates multiple signal transduction pathways related to tumor development (Abstract, page 675). In most aggressive metastatic cancers, expression of SGK1 is either upregulated or downregulated in various types of cancer including breast cancer and prostate cancer (Figure 1 and right col., page 678). Since dysregulation of SGK1 promotes an oncogenic environment in cells, there is reasonable expectation that the modified fusion protein would also be useful in treating cancer like breast cancer and prostate cancer. The rationale supporting obviousness is that combining prior art elements according to known methods yields predictable results.
Thus, claims 12-13 are obvious over Wang et al. in view of Aoyama et al. and Ghani.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie L. Gordon can be reached at (571) 272-8037. The fax phone number for the organization where this application is assigned is 571-273-8300.
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/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651
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