DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on August 11, 2026 is acknowledged.
Claims 13-16 have been added.
Claims 1-16 are pending.
Claims 5, 7, and 10-12 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 6, 2026.
Claims 1-4, 6, 8, 9, and 13-16 are currently under consideration as they read on the elected invention.
3. In view of applicant’s amendment, following rejections are set forth.
4. 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.
5. 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.
6. Claims 1-3 and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Vunnam et al. (US 5,585,278) in view of Ju et al. (Current Opinion in Biotechnology 2014, 30:128-139) and Leatherbarrow et al. (FEBS Letters, 1983, 164;2:227-230) for the reasons of record.
Vunnam et al. teach antibody-latex reagents prepared using a novel site-specific covalent linkage of the Fc region of the antibody onto the polymeric latex sphere substrates, thereby preserving the antigen binding sites of the antibody. Vunnam et al. teach that the immobilization of the antibody is essential for high specific activity and sensitivity assays and is also economical and much simpler than other covalent immobilizations (e.g. see Abstract and Examples). Vunnam et al. further teach that the core-shell latex particle consists of a thin outer shell of a polymerized aromatic vinyl monomer including polystyrene (e.g. see Table 1 in col. 6). Vunnman et al. teach that latex immune reagents are known to use poly(vinylbenzyl chloride) latex particles as the solid carrier for antibodies (e.g. see lines 59-67 in col.1 ). The antibody immobilization technique is simple, reproducible. It provides a stable site-specific covalent linkage between Fc moiety and the latex substrate, and it significantly improves the specific activity of antibody-latex; it is also cost effective (e.g. see lines 40-60 in col. 4).
In the working example, Vunnman et al. tach the average diameter of the final core-shell latex particles was about 223 nanometers (0.223 μm) (e.g. see Example 3).
The reference teachings differ from the instant invention by not describing aglycosylated antibody with no sugar chain bound to the heavy chain of the antibody.
Leatherbarrow et al. teach aglycosylated IgG does not have major structural alterations at the CH2 and CH3 interface of the Fc region of IgG and no differences were found in binding to protein A (e.g. see Abstract). Leatherbarrow et al. teach that this indicates that protein A-Sepharose can be used for purification of aglycosylated IgG in the same manner as for the parent IgG.
Ju et al. teach aglycosylated full-length IgG antibodies that are nearly identical to the glycosylated counter parts in terms of antigen binding, stability at physiological or low temperature conditions, pharmacokinetics, and biodistribution (e.g. see Abstract).
Ju et al. teach that in human IgGs, a complex N-glycan containing two highly dynamic branches is attached at each of Asn297 in the Fc regions (e.g. see 1st paragraph in left col. in page 130).
Ju et al. teach several humanized aglycosylated IgG1 antibodies against specific antigens and wherein the antibodies have a N297A mutation and aglycosylated antibody produced in E. coli (without N297A substitution) (e.g. see right col. in page 131).
Ju et al. teach that aglycosylated monoclonal antibodies can be produced in eukaryotic hosts without the drawbacks of glycan heterogeneity resulting in costly and challenging downstream steps for purification and quality control. In addition, the use of aglycosylated full-length IgG antibodies is a great choice for a range of applications as receptor blocking, and targeted delivery not requiring to activate Fc binding ligand while possessing the beneficial prolonged serum half-life of IgG relative to antibody fragments and reduced undesired inflammation and cytotoxicity (e.g. see page 129).
It would thus be obvious to one of ordinary skill in the art at the time the instant invention was filed to make a latex sphere immobilized with aglycosylated IgG antibody for immunoassays or immunodetection. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, because Vunnam et al. teach a novel site-specific covalent linkage of the Fc region of monoclonal IgG antibody to latex sphere that can be used as simple and economic immunoassay to detect antigen. Given that it was well known that therapeutic effects and benefit of aglycosylated IgG antibodies disclosed by Ju et al. and in view of the teachings of Leatherbarrow et al. that the removal of N-glycan in IgG does not affect the Fc properties in binding protein A, an ordinary skill in the art would be motivated to incorporate the aglycosylated therapeutic IgG to the latex beads for simple and sensitive methods disclosed by Vunnam et al. with a reasonable expectation of success.
Applicant’s arguments have been fully considered but not been found persuasive.
Applicant argues Leatherbarrow is directed to interaction between aglycosylated IgG and protein A but does not teach covalently coupling an antibody to a latex substrate. Applicant asserts that Vunnam et al. do not teach the use of protein A for immobilization.
Therefore, a glycosylated Fc that does not alter protein A binding would not be successfully acid-activated and covalently coupled to a latex substrate through its amino group under Vunnm’s condition because Vunnam neither use nor require protein A. Applicant further asserts that one of skill in the art would have no reason to combine Ju’s aglycosylated IgG with the Vunnam’s method with a reasonable expectation of success, since Ju teaches that aglycosylated IgGs display a low pH induced aggregation propensity and Vunnam requires acidifying the antibody to a pH about 2-4.
Applicant asserts that Alsenaidy et al. (J. Pharm Sci. 2014 June 103(6):1613-1627) teach nonglycosylated IgG Fc variants are more prone to aggregate at the acidic pH range of 4.0-6.0. Applicant thus asserts that one of skill in the art would not have reasonably expected to obtain latex particles based on Vunnma’s method involving acid treatment. As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
The reference Alsenaidy et al. cited by applicant was listed on PTO-892. A clearer copy is provided herein for convenience.
In response to applicant’s arguments against the references individually, one cannot show non-obviousness by attacking references individually where the rejections are based on combination of references. See MPEP 2145. IV.
Here, the question is not whether specific statements in the references themselves which would spell out the claimed invention exits. Rather, questions of obviousness involve not only what references expressly teach, but what they would collectively suggest to one of ordinary skill in the art. Vunnma et al. teach antibody-latex reagents prepared using a novel site-specific covalent linkage of the Fc region of the antibody onto the polymeric latex sphere substrates. It was also known that aglycosylated Fc does not alter its binding to the known binding partner such as protein A. Thus, an ordinary skill in the art would have been motivated to motivated to incorporate the aglycosylated therapeutic IgG to the latex beads for simple and sensitive methods disclosed by Vunnam et al. with a reasonable expectation of success.
Further, in contrast to applicant’s reliance on the teachings of Alsenaidy et al. regarding aggregation caused by an acidic condition for aglycosylated IgG, note that the methods of latex antibody conjugation are not performed in acidic condition. Rather, the conjugation is performed in pH8.1 (e.g. see Example 6 of Vunnam et al.).
While Vunnam et al. teach the use of acid to activate antibody for improved specific activity (e.g. see lines 45-50 in col. 4), the acid treatment only lasted 30-40 minute in room temperature and followed by increasing the pH to 7.5-7.9.
Applicant has not provided any objective evidence to show that the acidic treatment for 30 minutes in room temperature would result in aggregates that would not be dissolved when the pH is increased to pH7.5-7.9 for latex conjugation.
Furthermore, Alsenaidy et al. teach nonglycosylated mutant (QQ) demonstrated increased conformational stability compared to nonglycosylated DD and DN forms. Alsenaidy et al. teach the inter-relationships between aggregate formation and conformational stability are currently unclear and will need additional work (e.g. see last paragraph in left col. in page 1625).
Therefore, there is insufficient evidence that the teachings of Alsenaidy et al. regarding some difference in aggregation at lower pH of various non-glycosylated IgG would lead one of skill in the art to believe that the method of antibody latex conjugation disclosed by Vunnam et al. would not work for nonglycosylated IgG-latex particle conjugation.
As such, applicant’s arguments have not been found persuasive.
7. Claim 4, 6, 8, and 9 stand rejected under 35 U.S.C. 103 as being unpatentable over Vunnam et al. (US 5,585,278) in view of Ju et al. (Current Opinion in Biotechnology 2014, 30:128-139) and Leatherbarrow et al. (FEBS Letters, 1983, 164;2:227-230) as applied to claim 1 above, and further in view of Presta (US 6,737,056) and Chatterjee et al. (US 7,090,842) for the reasons of record.
Applicant’s arguments and the Examiner’s rebuttal are essentially the same as discussed above.
8. Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Vunnam et al. (US 5,585,278) in view of Ju et al. (Current Opinion in Biotechnology 2014, 30:128-139) and Leatherbarrow et al. (FEBS Letters, 1983, 164;2:227-230) as applied to claim 1 above, and further in view of Chaudhary et al. (Journal of Porous Materials 2019, 26:1559-1571).
The teachings of Vunnam et al., Ju et al., and Leatherbarrow et al. have been discussed, above.
The reference teachings differ from the instant invention by not describing divinylbenzene.
Chaudhary et al. teach polystyrene cross-linked with divinylbenzene with uniform particle size and porous structure has received significant interest due to their versatile application in the field of biotechnology (e.g. see left col. in page 1559). Chaudhary et al. teach that the variables including initiator, cross-linker, and diluent are most convenient variables to adjust the particle size distribution. Chaudhary et al. states that the polystyrene-co- divinylbenzene is one of the most suitable polymers used as catalyst support and can be synthesized in uniform (e.g. see left col. in page 1570).
It would thus be obvious to one of ordinary skill in the art at the time the instant invention was filed to cross link polystyrene latex particles disclosed in Vunnman et al. with divinylbenzene to create latex particles that would bind aglycosylated antibody disclosed by Leatherbarrow et al. and Ju et al. One of ordinary skill in the art would have been motivated to do so and have a reasonable expectation of success, because it was known that polystyrene cross-linked with divinylbenzene forms uniform particle size adjustable via convenient variables and is one of the most suitable polymers for biotechnology application. As such, incorporate divinylbenzene disclosed by Chaudhary et al. to cross link latex particles disclosed by Vunnman et al. to create a uniformed latex particle for that can bind aglycosylated antibody for immunopurification or immunodetection would be well within the skill of an ordinary artisan.
9. No claim is allowed.
10. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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