Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Claims
Claims 1-3 and 6-20 are pending. Claims 1 and 18-19 have been amended. Claims 4-5 are canceled. Claims 18 and 19 are withdrawn. Claim 20 is newly added. Thus, the claims in the prosecution are claims 1-3, 6-17, and 20.
New Rejections
Applicants' amendments have necessitated the following grounds of rejection:
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 35 U.S.C. § 103 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 6-17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Goldenberg et al. (US 20070292506 A1) evidenced by Guo et al. (Modular Assembly of Biomaterials Using Polyphenols as Building Blocks. ACS Biomater. Sci. Eng. 2019, 5, 5578-5596) in view of Yoshinaga et al. (JACS 2017, 139, 18567-18575, cited on IDS).
Goldenberg et al. disclose pharmaceutical formulation comprising a sustained release complex of a peptide of 20 amino acids or less and a purified gallic acid ester, wherein the complex is a salt of the peptide and the gallic acid ester (abstract, claims 1, 2). The formulation further comprises a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, or both (claim 3). The gallic acid ester is selected from the group consisting of penta galloyl glucose (PGG) and epigallocatechin gallate (EGCG) where gallic acid is 3,4,5 trihydroxybenzoic acid (abstract, claim 3). The compositions allow for sustained delivery of the protein or peptide in vivo upon administration of the complex ([0011], [0027]). The complex is a salt of the gallic acid ester and protein or peptide ([0012]).
Goldenberg et al. teach that while gallic acid esters are a known component of tannic acid, the disclosed formulation use of a highly purified component of tannic acids such as particular gallic acid esters to make a salt with peptides and polypeptides to advantageously create a sustained release formulation ([0014]). The terms "protein" and "peptide" are understood to include polymers of amino acids linked by amide bonds ([0015]). The terms encompass analogues and derivatives that mimic the chemical structure of the components of the protein or peptides ([0015]). Examples of analogues include peptides or proteins containing one or more non-natural amino acids and examples of derivatives include peptides or proteins containing amino acid side chain(s), peptide backbone, and/or amino- or carboxy-terminus that have been derivatized ([0015]). Here the prior art teaches gallic acid ester is a gallic acid derivative having diol structure and the protein taught is a specific type of substance claimed by instant claims.
Regarding the substance being bonded to the compound having a diol structure, Goldenberg et al. describes the protein's biological activity can be enzymatic or it may be a binding activity that confers conformation changes ([0015]). As evidenced by Guo et al., the interactions between polyphenols and proteins are facilitated by hydrophobic interactions and multiple hydrogen bonds wherein the catechol or galloyl groups that contain a hydrophobic moiety approach into the hydrophobic pocket of proteins via hydrophobic interactions and then the phenolic hydroxyl groups can interact with the polar groups, such as peptide linkages, hydroxyl groups, and carboxyl groups, to form two-point paired hydrogen bonds (page 5581, col. 1, para. 2). These two driving forces (i.e., hydrophobic interactions and hydrogen bonding) work together to form stable polyphenol−protein complexes (page 5581, col. 1, para. 2).
Goldenberg et al. differ from the instant claims in that boronic acid group is not taught.
However, Yoshinaga et al. teach phenylboronic acid delivery systems of DNA payloads.
Yoshinaga et al. disclose a plasmid DNA (pDNA)-loaded polyplex micelles (PMs) from poly (ethylene glycol)-based block catiomers derivatized with 4-carboxy-3-fluorophenylboronic acid (FPBA) group and D-gluconamide to form pH- and ATP-responsive cross-linking in the core (title, abstract, pg. 18569, Scheme 3). Here the FPBA group is introduced in the side chain of the platform catiomer of block copolymers. The PBA-modulated delivery systems bind to diols (i.e., gluconamide) as tetravalent boronate selectively forms stable ester linkages with diol compounds in aqueous solutions; facilitated by an increase in both pH and concentration of diol compounds (pg. 18568, para. 1; Scheme 1). (See Scheme 1 provided below). Here the prior art of Yoshinaga et al. reads on the polymer having a boronic acid group bonded to a compound having a diol structure.
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The FPBA crosslinked PMs bond with diol groups via cellular entry (i.e., endosome) (pg. 18568, Scheme 2). Yoshinaga et al. provide synthetic schemes of complexes comprising poly (ethylene glycol), FPBA, and poly{N′-[N-(2-aminoethyl)-2-aminoethyl]-aspartamide} (PAsp (DET)) as shown in Scheme 3 in part provided below (pg. 18569).
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Yoshinaga et al. teach that FPBA enhances the endosomal escapability of the PMs and contributes to promoted gene transfection (abstract; pg. 18567, col. 2, para. 2). Yoshinaga et al. teach that the PBA are pH-responsive and change in hydrophobicity and diol-binding ability thereby increasing transfection efficiency (pg. 18568, para. 1).
Regarding claims 1-3 and 20, it would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention to incorporate the boronic acid group taught by Yoshinaga et al. in the composition of Goldenberg et al. for the delivery of a substance bonded to the compound having the diol structure, that substance being a protein. One would be motivated to do so with expected results because as Yoshinaga et al. teach DNA (i.e., protein) payloads, Goldenberg et al. provide compositions that are useful in the formulations of other types of proteins and highlight DNA molecules ([0021]). As mentioned above, Goldberg et al. teach protein to include polymers of amino acids linked by amide bonds; encompass analogues and derivatives ([0015]). Phenylboronic acid groups and polymers, specifically block copolymers containing boronic acid taught by Yoshinaga et al. provide enhanced drug control and delivery. This teaching complements Goldenberg et al. which acknowledges the difficulty of maintaining the integrity of the active agent during manufacture is as most protein and peptide drugs are dependent on a three-dimensional conformation for their bioactivity and that conformation can easily be compromised ([0008]).
Regarding claim 6, Yoshinaga et al. show two boronic acid groups in TPEG-b-PAsp (DET/FPBA) as seen below (pg. 18569, see product in Scheme 3).
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Regarding claims 7 and 8, Yoshinaga et al. teach 4-carboxy-3-fluorophenylboronic acid (FPBA) (abstract, pg. 18568, col. 2, Scheme 2). As shown above, F (i.e., fluorine) represents the halogen, X.
Regarding claims 9 and 12, (i.e., polyethylene glycol) Yoshinaga et al. teach PEG in the reactant as highlighted below (pg. 18569, para. 1, see reactant in Scheme 3).
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Regarding claim 10 (i.e., different 1st and 2nd biocompatible polymer chains), and claim 11 (i.e., BA in the side chain of polyamino acid), Yoshinaga et al. teach FPBA as being introduced in the side chain of the platform catiomer of block and teaches aspartamide (Asp) (pg. 18569, col. 1, para. 1; Scheme 3). Brooks et al. disclose L-lysine as a second polymer chain (pg. 1383, col. 2), and boronic acid-modified poly(lysine) (pg. 1386, Fig. 18).
Regarding claim 13 (i.e., A-B, 1-1), Yoshinaga et al. teach the number of repeating units is 75 (shown above) making the number of boronic acid groups equal to that of the biocompatible polymer chain (pg. 18569, Scheme 3). Brooks et al. teach cross-link density is a function of both boronic acid and diol content (pg. 1377, col. 2, para. 2).
Regarding claim 14 (i.e., 5 nm – 200 nm), Yoshinaga et al. teach that dynamic light scattering (DLS) measurement of the samples prepared from all of the combinations of block catiomers indicated the formation of particles with cumulant diameter of 75−96 nm (pg. 18569, col. 2, last para.). MPEP 2144.05 states that a prima facie case of obviousness exists in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art.
Regarding claim 15 (i.e., 2,000 – 200,000 g/mol), Yoshinaga et al. describe the synthesis in the results section 2 of how the introduction of ratios of FPBA were systematically varied to achieve and optimize stabilization and responsivity of PMs to pH and ATP (pg. 18569, section 2.2.; see also Supporting Information SI 2.2 detailed procedure). MPEP 2144.05 states that 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. A person skilled in the art would obtain a molecular weight that falls within the claimed range by optimizing the repeating units of the polymer.
Regarding claims 16 and 17, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. Here, the intended use is medicine in claim 16 and a therapeutic agent for cancer in claim 17. If the prior art structure is capable of performing the intended use, then it meets the claim limitation(s).
Response to Arguments
Applicants’ arguments are based on newly amended limitations which have been addressed by the new grounds of rejection above.
Conclusion
All claims under consideration remain rejected; no claims are allowed. Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for replying to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no case, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Karen Ketcham whose telephone number is (571)270-5896. The examiner can normally be reached 0830-1630.
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/Karen A Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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