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 Jul. 23, 2026. Claims 1, 2, 4-7 and 9-27 are pending. Claims 5, 7, 10, 12, 13, 15-16 and 19-27 are withdrawn.
Claims 1-2, 4, 6, 9, 11, 14 and 17-18 are currently examined for the following species:
1) TLR7 (claim 4), and more specifically, 1H-imidazo[4,5-C]quinoline-1- propanamine,4-amino-2-(ethoxymethyal (claim 6), for the agonist module (X);
2) a succinimide derivative (claim 1), and more specifically N-(ε- maleimidocaproyloxy) succinimide ester (claim 9), for the linker unit (L); and
3) from xenogenic source (claim 11), specifically, a viral antigen (claim 14), and more specifically, hemagglutinin (HA) of influenza A virus (claims 17-18), for the antigen (Y).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(New Rejection – Necessitated by Amendment) Claims 1-2, 4, 6, 9, 11, 14 and 17-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The base claim 1 is amended to recite “the immunogenic conjugate is coupled to the outer surface of the nanodiamond and has a configuration in which the antigen is proximal to the nanodiamond, and the agonist module is distal to the nanodiamond”. The specification teaches “[I]n some embodiments, the immunogenic conjugate having been adsorbed onto the outer surface of nanodiamond has a configuration in which the antigen is proximal to the nanodiamond, and the agonist module is distal to the nanodiamond. In some preferred embodiments, the immunogenic conjugate is adsorbed onto the outer surface of nanodiamond via a hydrophobic interaction between the antigen and the nanodiamond.” However, neither the specification nor the claims clearly and exclusively define the configuration as claimed. E.g., it is not clear if the newly added limitation specifies that the coupling must be mediated by interaction between the antigen module in immunogenic conjugate molecule and the outer surface of the nanodiamond, instead of between the agonist module and the outer surface of the nanodiamond. Additionally, it is not clear if the newly added limitation encompasses a scenario where some of the immunogenic conjugate molecules are coupled to the outer surface of nanodiamonds via interaction between the antigen module and the outer surface of nanodiamonds while some are coupled via interaction between the agonist module and the outer surface of nanodiamonds.
The specification teaches that the immunogenic composition was prepared by mixing solution of immunogenic conjugates with NDs (nanodiamonds) in PBS at room temperature, and the mixture was shaken for 1 hour until certain amounts of immunogenic conjugates were non-covalently conjugated with NDs, resulting aggregation of the immunogenic conjugates on the surface of NDs. See [0085].
To facilitate examination, the newly added limitation is interpreted as reading on the scenario where some of the immunogenic conjugate molecules are coupled to the outer surface of nanodiamonds via interaction between antigen module and the outer surface of nanodiamonds.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
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 of this title, 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.
(Previous Rejection – Maintained) Claims 1, 2, 4, 11, 14 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Pham et al. (J Nanobiotechnol (2017) 15:69) in view of Van Hoeven et al. (Scientific Reports, 2017, 7:46426), and further in view of Vecchi et al. (European Journal of Pharmaceutics and Biopharmaceutics 87 (2014) 310–317) and Wu et al. (P.N.A.S., 2007, 104: 3990-3995).
These claims, as amended, are directed to an immunogenic composition, comprising: a nanodiamond; and an immunogenic conjugate of formula (I): X-L-Y, wherein X is an agonist module, L is a linker unit, and Y is an antigen, wherein, the immunogenic conjugate is coupled to the outer surface of the nanodiamond and has a configuration in which the antigen is proximal to the nanodiamond, and the agonist module is distal to the nanodiamond, the agonist module is a Toll-like receptor (TLR) agonist, and the linker unit is a succinimide derivative or a PEG-based compound.
Pham teaches a study using nanodiamond nanoparticles to enhance immune responses in mice against influenza A H7N9 hemagglutinin (HA) protein. In this study, the trimeric HA protein solution was mixed with a nanodiamond suspension. Successful conjugation of the trimeric HA onto the surface of nanodiamond particles was demonstrated by the changes in size and Zetapotential of the particles before and after protein coating, Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and Western-blot analysis. Next, biofunction of the protein-nanodiamond conjugates was screened using a hemagglutination assay. After the 2nd and 3rd immunization in mice, ELISA and Western blot analyses demonstrated that the physical mixture of trimeric HA protein and nanodiamond (1:12, w/w) elicited statistically significant stronger HA-specific-IgG response demonstrated by higher amounts of H7N9-specific IgG (over 15.4-fold with P < 0.05 after the second immunization). These results indicated a potential effect inherent to nanodiamond towards modulating immune systems, which should be further evaluated and broadly applied in nanovaccine development. See Abstract.
Accordingly, Pham teaches an immunogenic composition comprising nanodiamond nanoparticles and influenza A virus antigen HA, wherein the HA antigen is coupled to the outer surface of the diamond. However, Pham is silent on if the HA antigen can be comprised in an immunogenic conjugate of formula (I): X-L-Y, as claimed.
Van Hoeven teaches a study on formulating a TLR7/8 agonist with influenza vaccines as adjuvant. Van Hoeven describes adjuvant formulation development of the imidazoquinoline TLR-7/8 agonist 3M-052, in combination with H5N1 hemagglutinin (HA) based antigens. The authors find that 3M-052 in multiple formulations protects both mice and ferrets from lethal H5N1 homologous virus challenge. Furthermore, they demonstrate the ability of 3M-052 adjuvant formulations to broaden responses to H5N1 HA based antigens, and show that this broadening is functional using a heterologous lethal virus challenge in ferrets. See Abstract.
Van Hoeven teaches that the ability of imidazoquinolines to target Toll-like Receptor TLR7 and/or TLR8 to generate enhanced innate immune responses has been well documented (Reviewed in ref. 47). As synthetic small molecules, imidazoquinolines can be manufactured cost effectively and at high purity. The TLR7 ligand imiquimod is the active component in the topical cream Aldara® , approved for human immunotherapeutic use to treat skin cancer and genital warts. However, use of injected imidazoquinolines as vaccine adjuvants have not progressed beyond clinical testing. Due to their small size, it is supposed that soluble, unformulated imidazoquinolines such as R848 rapidly diffuse from the injection site, potentially causing systemic immune activation rather than localized stimulation. For this reason, strategies to “slow down” diffusion such as covalent conjugation to vaccine antigens or encapsulation in particulate formulations have shown promise in preclinical testing. The authors describe the formulation development and influenza vaccine adjuvant activity of liposome and emulsion-based formulations of 3M-052. They find that 3M-052 based adjuvants increase the protective capacity of H5N1 antigens, promoting broadening of antibody responses, antigen dose sparing and protection in multiple pre-clinical models. See page 2, para 4.
Figure 1 of Van Hoeven, showing the chemical structure of the TLR7 agonist 3M-052, is presented below:
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Accordingly, Van Hoeven teaches the concept and practice of using an imidazoquinoline-based TLR7 agonist, 3M-052, as an adjuvant for influenza A virus vaccine antigens. Van Hoeven further suggests that such small molecule TLR7 agonists may be conjugated to vaccine antigens or included in nanoparticle carriers to help keep them in the desired locations (“slow down” their systemic diffusion).
Vecchi teaches a study on conjugating a TLR7 agonist and antigen from S. pneumoniae, showing that the conjugation enhances protection in a murine infection model. See Abstract.
Vecchi teaches that the effect of direct co-localization of TLR7 agonist and Ag was shown by different works by Wille-Reece et al. in mice and in non-human primates, by UV-catalyzed conjugation of the TLR7/8 agonist 3M-012 (structurally similar to R848) to the Gag protein from HIV. This conjugate showed enhanced Th1 and CD8+ T cell responses, demonstrating that the TLR7/8 agonist could be a useful adjuvant to increase cytokine production in vivo when administered as protein conjugate. The increased efficiency of DCs activation rather than prolonged duration of Ag presentation has been suggested to be the mechanism by which the Ag-TLR7/8 conjugate enhances T cell responses in vitro. See page 311, left column, para 5.
Vecchi further teaches that a study from Wu et al. (see description below) showed the effect of conjugating of a TLR7 ligand (UC-1V150) to mouse serum albumin (MSA). The MSA was activated with a hydrazine linker (SANH), and the respective derivative was conjugated to the TLR7 ligand. The effect of the TLR7 induced Th1 and Th2 antigen specific immune response and extended mice survival after challenge with Bacillus anthracis spores. See page 311, left column, para 6.
Wu teaches a study on immunotherapeutic activity of a conjugate containing a TLR7 ligand and an antigen. Wu teaches that the immunotherapeutic activity of Toll-like receptor (TLR) activators has been difficult to exploit because of side effects related to the release and systemic dispersion of proinflammatory cytokines. To overcome this barrier, the authors have synthesized a versatile TLR7 agonist, 4-[6-amino-8-hydroxy-2-(2-methoxyethoxy)purin-9-ylmethyl] benzaldehyde (UC-1V150), bearing a free aldehyde that could be coupled to many different auxiliary chemical entities through a linker molecule with a hydrazine or amino group without any loss of activity. UC-1V150 was covalently coupled to mouse serum albumin (MSA) at a 5:1 molar ratio to yield a stable molecule with a characteristically altered UV spectrum. Compared with the unconjugated TLR7 agonist, the UC-1V150/MSA was a 10- to 100-fold more potent inducer of cytokine production in vitro by mouse bone marrow-derived macrophage and human peripheral blood mononuclear cells. When administrated to the lung, the conjugate induced a prolonged local release of cytokines at levels 10-fold or more higher than those found in serum. See Abstract.
Wu teaches that the free aldehyde group on the benzyl moiety of UC-1V150 enabled them to couple the agonist to many different auxiliary chemical entities, including proteins, oligonucleotides, aromatic molecules, lipids, viruses, and cells, through a linker molecule that contained a hydrazine or amino group. UC-1V150 was covalently coupled to MSA first modified with a succinimidyl 6-hydrazino-nicotinamide acetone hydrazone (SANH) linker to yield a stable molecule with a characteristically altered UV spectrum (Fig. 2). See page 3990, right column, para 2.
Accordingly, both Vecchi and Wu teach conjugating TLR7 agonists to protein antigens. Wu further teaches that a succinimidyl 6-hydrazino-nicotinamide acetone hydrazone (SANH) linker is involved in the conjugation between the TLR7 ligand/agonist and the protein antigen. Here, the SANH linker is considered to read on the succinimide derivative linker unit specified in claim 1.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Pham, Van Hoeven, Vecchi and Wu to arrive at the invention as claimed. One would have been motivated to introduce a TLR7 agonist into the study of Pham as adjuvant of the influenza vaccine, as taught in Van Hoeven; One would also have been motivated to conjugate the TLR7 agonist to the vaccine antigen to maintain the TLR7 agonist in desired locations (e.g., to locate with the antigen and to “slow down” systemic dissemination), as suggested in Van Hoeven and disclosed in Vecchi and Wu. There would have been reasonable expectation of success that the TLR7 agonists disclosed in Van Hoeven, Vecchi and/or Wu can be conjugated to the influenza A HA antigen in the study of Pham based on the teachings of Vecchi and Wu.
Regarding the new limitation that the immunogenic conjugate is coupled to the outer surface of the nanodiamond and has a configuration in which the antigen is proximal to the nanodiamond, and the agonist module is distal to the nanodiamond, Pham teaches that the H7:ND complexes were synthesized via a simple mixing of protein solution and ND suspension for 1 h under sonication. Different Protein/ND ratios (w/w) (1:1, 1:3, 1:5, 1:7, 1:9, 1:12 and 1:15) were tested to find the best synthetic condition. Figure 4 shows the changes in the size distribution of ND before and after coating with trimeric H7 protein at a 1:1 (w/w) ratio. The protein-coated ND samples were re-suspended in both DI-H2O and 1 × PBS for the particle size measurements. It can be clearly seen from Fig. 4a, b that ND particles increase in size to approximately 80 nm in diameter after protein coating. See page 6, right column, para 2. This teaching indicates that the formation of the HA protein antigen-coated nanodiamond complex is achieved by simple mixing of protein antigen solution and nanodiamond suspension. One of skill in the art would readily envisage that the coating is by interaction between the protein and the surface of the nanodiamond. Additionally, one of skill in the art would also expect that coupling of immunogenic conjugate molecules, comprising an antigen (e.g., HA), a linker, and a TLR agonist, to nanodiamonds, suggested by the combined teachings of Pham, Van Hoeven, Vecchi and Wu, would involve, at least partially, the interaction between the antigen module and the outer surface of the nanodiamonds, if the coupling conditions taught in Pham are used (i.e., simple mixing of the antigen solution and NDs).
Claims 6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Pham et al. (J Nanobiotechnol (2017) 15:69) in view of Van Hoeven et al. (Scientific Reports, 2017, 7:46426), Vecchi et al. (European Journal of Pharmaceutics and Biopharmaceutics 87 (2014) 310–317) and Wu et al. (P.N.A.S., 2007, 104: 3990-3995), as applied above, further in view of Vernejoul et al. (US 2014/0141033 A1, published on May 22, 2014) and/or Thompson ("Small-molecule-protein conjugation procedures." Molecular diagnosis of infectious diseases. Totowa, NJ: Humana Press, 2004. 255-265).
Claim 6 species that the TLR7 agonist is 1H-imidazo[4,5-C]quinoline- 1 -propanamine,4-amino-2-(ethoxymethyl). Claim 9 specifies that the succinimide derivative is N-(e-maleimidocaproyloxy) succinimide ester or N-g- maleimidobutyryl-oxysuccinimide ester.
Relevance of Pham, Hoeven, Vecchi and Wu is set forth above. However, they are silent on the specific TLR7 agonist and succinimide derivative linker unit specified in claims 6 and 9.
Vernejoul teaches an invention relating to conjugates comprising TLR7 agonists. See Abstract. It teaches various compounds having TLR agonist functions. See structures throughout the specification. Vernejoul teaches the structure of a compound, 1-(3-aminopropyl)-2-(ethoxymethyl)-1H-imidazo4,5-c]quinolin-4-amine, that is indistinguishable from the claimed 1H-imidazo[4,5-C]quinoline-1-propanamine,4-amino-2-(ethoxymethyal), in claim 6, suggesting that the claimed compound is known in the art as a potential TLR7 agonist. See page 31, left column. The structure is presented below:
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Thompson teaches protocols for small-molecule-protein conjugation. Thompson teaches that N-(maleimidocaproyloxy)succinimide ester (EMCS) can be used in the conjugation process. See page 256.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to introduce the TLR7 agonists disclosed in Vernejoul, and/or the linker unit disclosed Thompson, including the ones as claimed, into the study suggested by the combined teachings of Pham, Van Hoeven, Vecchi, and Wu, because these TLR7 agonists and linker units are known as the time of invention to have the same functions. Such a combination, or a substitution of one element for another known in the field to have the same function, is evidence that the claimed invention may be found obvious. See MPEP 2144.06 and KSR International v. Teleflex Inc., 82 U.S.P.Q.2d 1385, at 1395. Therefore, the instant invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Applicant’s Arguments
Applicant’s arguments and Declaration filed on Jul. 23, 2026 have been fully considered and addressed as follows.
To the 103 rejection of claims 1, 2, 4, 11, 14 and 17-18, Applicant argues that the Examiner’s asserted combination of the cited references is merely a speculation without a proper scientific basis, thus would not have provided a skilled artisan with a reasonable motivation to arrive at the presently claimed immunogenic composition. Applicant argues based on the following two aspects:
A. The determination of obvious is based on hindsight analysis.
Applicant argues that the Examiner did not articulate a sound reasoning that would prompt a skill artisan to combine Van Hoeven, Vecchi or Wu with Pham to arrive at the presently claimed immunogenic composition. Applicant supports this argument with a Declaration from an inventor, Dr. Lin.
B. The Examiner has not shown the elements being combined modified produce a predictable result.
Applicant argues that, in the present case, even if the cited references were combined, the proposed modification would not have been predictable, and that the Examiner does not provide a sufficient technical explanation as to why the proposed combination would have reasonably been expected to maintain the relevant antigen configuration and immune response in Pham.
Applicant supports this argument with a Declaration from an inventor, Dr. Lin, arguing that covalently conjugating a TLR agonist to trimeric H7 protein would not have provided a predictable expectation of success. Applicant refers to Xu et al. (Protein Science, 2009, vol. 18, pp. 2100-2114), reporting that coiled-coil assembly can be context-dependent, and that small changes in sequence or structural context can alter oligomerization state. Applicant argues that, given that GCN4-pII (GCN4-pII is a trimeric heptad repeat sequence which was fused to H7 in Pham for trimerization of the H7) was described as a canonical three-stranded coiled-coil and that such assemblies are sensitive to contextual modifications, the assembly state of Pham’s GCN4-pII-fused trimeric H7 could not have been expected to remain unchanged after additional modification.
Applicant’s arguments are not persuasive.
As to Applicant’s argument A, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In this case, the rejection has explained why a skilled artisan would have been motivated to develop the claimed immunogenic composition without taking into account “knowledge gleaned only from applicant’s disclosure.” McLaughlin, 443 F.2d 1395.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Pham, Van Hoeven, Vecchi and Wu to arrive at the invention as claimed. One would have been motivated to introduce a TLR7 agonist into the study of Pham as adjuvant of the influenza vaccine, as taught in Van Hoeven; One would also have been motivated to conjugate the TLR7 agonist to the vaccine antigen to maintain the TLR7 agonist in desired locations (e.g., to locate with the antigen and to “slow down” systemic dissemination), as suggested in Van Hoeven and disclosed in Vecchi and Wu. There would have been reasonable expectation of success that the TLR7 agonists disclosed in Van Hoeven, Vecchi and/or Wu can be conjugated to the influenza A HA antigen in the study of Pham based on the teachings of Vecchi and Wu.
As to Applicant’s argument B, even though the reference Xu cited by Applicant teaches that the results of the study emphasize the degenerate nature of coiled-coil energy landscapes in which small changes can have drastic effects on oligomerization, its teachings are focused on the native ion channel assembly domain and prevalence of the R-h-x-x-h-E motif in coiled-coil assembly domains of a number of different channels that are thought to function as tetrameric assemblies raises the possibility that such sequence features may be important for facilitating the assembly of intermediates en route to the final native state. See Abstract. However, the trimers formed by H7- GCN4-pII fusion protein are native ion channel proteins. Additionally, it is known in the art that GCN4-pII is an engineered, stable trimeric coiled-coil peptide derived from the leucine zipper domain of the yeast transcription factor GCN4. See e.g. Alvarez et al. (Protein Engineering, Design & Selection vol. 21 no. 1 pp. 11–18, 2008). Therefore, there is no evidence that the study results generated in Xu for coiled-coil domains in native ion channel proteins are relevant to the trimers of H7- GCN4-pII fusion protein which are based on the stable trimeric coiled-coil peptide derived from the leucine zipper domain of the yeast transcription factor GCN4. Moreover, Xu does teach or suggest what would happen to protein multimers formed by GCN4-pII when conjugating a TLR agonist.
Based on the known information about the GCN4-pII domain, one of skill in the art would have reasonably expected that the trimers mediated by the GCN4-pII domain are stable and would maintain the conformation in a conjugation process, at least, in absence of evidence to the contrary. Additionally, the rejection does not require exactly the trimeric H7- GCN4-pII to be conjugated to nanodiamonds. Both Vecchi and Wu teach conjugating TLR7 agonists to protein antigens to enhance the immunogenic properties of protein antigens. One of skill in the art would have found it obvious to combine the nanodiamond particles of Pham with the antigen-TLR agonist conjugate of Vecchi and Wu so that advantage of two components would be combined.
And, results of such a combination of antigen-TLR agonist conjugate and nanodiamond particles would be reasonably predictable based on the teachings of the cited prior art. Obviousness does not require absolute predictability. See MPEP 2143.02 II.
To the 103 rejection of claim 9, Applicant argues that the Examiner’s assertion based on Thompson is speculative and lacks a proper scientific basis. Applicant argues that Thompson does not support the predictability of the Examiner’s proposed modification; rather it highlights the risk that such conjugation may inactivate proteins, thereby underscoring the unpredictability of the outcome. In the Declaration, Dr. Lin argues that Thompson directly undermines the predictability of such conjugation, that Thompson notes that conjugation via amine groups (e.g., using succinimide-based linkers) can inactivate proteins if susceptible amine residues are located in binding regions, and that, when combined with Xu, this supports Dr. Lin’s opinion that using a succinimide linker to attach a TLR agonist to Pham’s GCN4-pII-fused antigen would be highly unpredictable and prone to failure.
Applicant’s arguments are not persuasive. As indicated above, obviousness does not require absolute predictability. See MPEP 2143.02 II. Xu does not provide evidence that its results, generated for native coiled-coil domains in ion channel proteins, are relevant to the GCN4-pII motif, which are based on the stable trimeric coiled-coil peptide derived from the leucine zipper domain of the yeast transcription factor GCN4. Additionally, Applicant does not articulate what is highly unpreditictable and prone to failure relating to conjugating an antigen to a TLR agonist using the succinimide-based linkers taught in Thompson. It is noted that, to function as an immunogenic composition for inducing immune response in a host, the antigen does not need to maintain the entire native structure of the antigen protein.
Applicant further argues that the amended claims are not obvious. Applicant argues that Pham, Van Hoeven, Vecchi and Wu do not teach or suggest the newly added limitation that the claimed composition “has a configuration in which the antigen is proximal to the nanodiamond, and the agonist module is distal to the nanodiamond.”
In the Declaration, Dr. Lin argues that a skilled artisan would actively avoid this configuration in light of Pham’s teachings, because Pham emphasizes that outward exposure of the antigen on the nanodiamond surface is critical for immune recognition, that covalently linking a TLR agonist to the exterior of the antigen (thereby rendering the agonist distal and antigen proximal) would sterically mask the antigen’s epitopes. Dr. Lin argues that the prior art does not render obvious the specific use of a succinimide/PEG linker in the proximal/distal orientation, PEG is widely recognized in the art to sterically mask both agonist and the adjacent antigen. Applicant argues that achieving the claimed linear configuration (ND-Antigen-PEG-Agonist) requires reacting a succinimide group directly with the surface lysines, one of skill in the art would expect this reaction to disrupt the critical trimeric folding of the GCN4-pII antigen taught by Pham.
Applicant’s arguments are not persuasive.
The newly added limitation is addressed in the 112(b) and 103 rejections. Briefly, teachings of Pham and the instant specification indicating that the coupling of the antigen and NDs are achieved by simple mixing of antigen solution with the NDs, suggesting that the coupling involved directing interaction of the antigen with the outer surface of NDs (leading to the proximal location of the antigen relative to NDs), and the distal location of the agonist module, if any, relative to the NDs. As to the argument that PEG may sterically mask both agonist and the adjacent antigen, Applicant has not provided any evidence to support this argument. On the other hand, the rejection is directed to the elected species of succinimide derivative as linker unit, not PEG, so the argument is not germane to the rejection.
Conclusion
No claims are allowed.
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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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