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
Acknowledgement is hereby made of receipt and entry of the communication filed on Jan. 05, 2026 and Sep. 22, 2022. Claims 1-21 are pending. Claims 2-3 and 9-21 are withdrawn. Claims 1 and 4-8 are currently examined.
Election/Restrictions
Applicant's election without traverse of Group I (Claims 1 and 4-8) in the reply filed on Jan. 05, 2026, is acknowledged. Accordingly, claims 2-3 and 9-21 are withdrawn as being directed to a non-elected Group.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites abbreviation “GRFT” without spelling it out the first time it appears in the claims set. Appropriate correction is required.
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.
Claims 1 and 4-8 are rejected under 35 U.S.C. 103 as being unpatentable over O’Keefe et al. (US 8,088,729 B2, patented on Jan. 3, 2012, submitted in IDS filed on 01/06/2023) as evidenced by Steinbach-Rankins et al. (US 2019/0083569 A1, published on Mar. 21, 2019, submitted in IDS filed on 01/06/2023), Moulaei et al. (Structure. 2010 Sep 8;18(9):1104-15) and Ziółkowska et al. (Structure. 2006 Jul;14(7):1127-35).
The base claim 1 is directed to an engineered GRFT polypeptide lacking lysines ("-K GRFT").
O’Keefe teaches an engineered GRFT polypeptide for inhibiting prophylactically or therapeutically a viral infection of a host (See column 4; column 11 lines 43-50). Although O’Keefe does not explicitly teach the engineered GRFT polypeptide lacking lysines ("-K GRFT"), O’Keefe teaches that it is within the skill of the ordinary artisan to select synthetic and naturally-occurring amino acids that effect conservative or neutral substitutions for any particular naturally occurring amino acids. The ordinarily skilled artisan desirably will consider the context in which any particular amino acid substitution is made, in addition to considering the hydrophobicity or polarity of the side-chain, the general size of the side chain and the pK value of side-chains with acidic or basic character under physiological conditions. For example, lysine, arginine, and histidine are often suitably substituted for each other because natural Griffithsin forms dimers, which is critical for the anti-viral function of the polypeptide and mutations that do not modify the electronic or structural environment of the peptide are generated to retain optimal antiviral activity (See column 7, lines 7-67). This can be evidenced by Steinbach-Rankins’s study. Steinbach-Rankins teaches that there are only two lysine residues, Lys6 and Lys99, in the primary sequence of GRFT (i.e. four per GRFT dimer molecule), of which the latter is buried near the interface between two monomers of the domain-swap dimer structure; hence, there may be steric hindrance of two of the four lysine residues within the GRFT protein, resulting in insufficient primary amine groups available for conjugation (paragraph (0107]). Accordingly, one of skilled in the art, at the time of the invention, can implemented an engineered GRFT polypeptide lacking lysine to overcome these challenges. Because the mutation or substitution technique is an ordinary skill in the art, there would be a reasonable expectation of success to make the Lysine substitution to generate a GRFT lacking lysines to improve GRFT conjugation efficiency while ensuring that GRFT antiviral activity is maintained (See [0107]). This can be evidenced by Moulaei’s study. Moulaei et al. teaches that various mutant forms of GRFT including Lys6 (K6) mutation (S65W, S65W/S106E, E119I/S65Y, K6V/S65Y, L2V/S65Y), which kept the dimer-structure and did not form monomers, retained potent anti-HIV activity (See Table 4, page 8), advantageous in some embodiments. Therefore, alterations which do not disrupt dimer formation can be preferred. Amino acid residues which are not responsible for folding or stability of the three-dimensional conformation of the Griffithsin polypeptide are candidate residues for mutation (See Column 7, lines 36-55). This can be further evidenced by Ziółkowska’s study. The Figure 1 of Ziółkowska et al. indicates that the Lys6 and Lys99 are both not among the critical structure amino acids based on the structure-based sequence alignment (See page 1128, and Figure 1 and below).
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Regarding claims 4-5, O’Keefe teaches that a Griffithsin conjugate comprising a Griffithsin coupled to at least one effector component, which can be the same or different (See column 9, lines 9-38). Although O’Keefe does not teach the nanoparticle conjugation, Steinbach-Rankins teaches that the GRFT is conjugate to EF (electrospun fiber) (see Figs. 4A-4B) and the EF fiber can be comprised of PLGA (See [0053]) and it was discovered that unmodified PLGA EFs completely inhibited HIV penetration for up to 3 days under those administration conditions in vitro (FIG. 9) (See [0099]). It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of O’Keefe, Steinbach-Rankins and Moulaei to arrive at an invention as claimed. One of skill in the art would be motivated to conjugate the CRFT lacking lysine in O’Keefe with the PLGA EF to increase the capability of HIV-infection inhibition. There would be a reasonable expectation of success to develop such an engineered GRFT polypeptide as claimed based on the teachings of Steinbach-Rankins and Moulaei.
Regarding claim 6, O’Keefe teaches that the solid support matrices can be used, such as a matrix comprising a porous surface or membrane, over or through which a sample is flowed or percolated, thereby selectively entrapping or removing infectious virus from the sample (See column 29, lines 1-32), and the functional Griffithsin can be attached onto a solid support matrix (See column 16, lines 15-43).
Regarding claim 7, O’Keefe teaches that the Griffithsin can be covalently coupled to a solid support matrix via an anti Griffithsin antibody, described below. Methods of attaching an antibody to a solid support matrix are well-known in the art (see, for example, Harlow and Lane. Antibodies: A Laboratory Manual, Cold Springs Harbor Laboratory: Cold Spring Harbor, N.Y. (1988)) (See column 27, lines 4-39), where the methods of attaching an antibody to a solid support matrix is the fundamental principle of a lateral flow test.
Regarding claim 8, O’Keefe teaches other types of solid support matrices can be used, such as a matrix comprising a porous surface or membrane, over or through which a sample is flowed or percolated, thereby selectively entrapping or removing infectious virus from the sample (See column 29, lines 10-32), where the porous membrane can be a cellulose or nitrocellulose strip.
Conclusion
No claims are allowed.
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/RUIXUE WANG/ Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1672