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 .
Claim Status
The amended claim set filed on 28 May 2026 is acknowledged. Claims 48-68 are currently pending. Of those, claims 48 and 58 are amended. There are no new claims, and claims 58-68 are withdrawn. Claims 48-57 will be examined on the merits herein.
Response to Amendment
Applicants’ arguments filed 28 May 2026 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks”, and the Non-Final Office Action mailed 28 January 2026 will be referred to as “NFOA”.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 28 May 2026 was filed after the mailing date of the NFOA on 28 January 2026. The submission is in compliance with the provisions of 37 CFR 1.97 because the appropriate fee was paid. Accordingly, the information disclosure statement is being considered by the examiner.
Rejection(s) Withdrawn
The rejection of claims 48, 51-52, and 56-57 under 35 U.S.C. 102 is withdrawn in view of the claim amendments.
Rejection(s) Maintained
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 103
Claims 48-52 and 54-57 remain rejected under 35 U.S.C. 103 as being unpatentable over Eliasson et al. (2008, Vaccine; herein “Eliasson”) in view of Chen et al. (2018, Immunol. Lett.; herein “Chen”).
The previous rejection has been amended to reflect the claim amendments.
Regarding claims 48-50 and 54-57, Eliasson teaches a fusion protein comprising the A1 subunit of cholera toxin (CTA1-DD) and the ectodomain of the matrix protein 2 (M2e) of influenza A (pg. 274, left col., para. 2). Eliasson does not teach that the CTA1 protein itself has been modified; therefore, the CTA1 is enzymatically active (pg. 1244, paragraph bridging columns). Eliasson teaches that the fusion protein was produced by transforming an expression vector encoding CTA1-M2e-DD (i.e., a nucleotide sequence comprising a nucleotide sequence encoding CTA1 and a nucleotide sequence encoding M2e) into E. coli DH5 cells (i.e., cells comprising the nucleotide sequences encoding CTA1 and M2e) (pg. 1244-1245, paragraph bridging pages). Eliasson also teaches that the fusion protein is able to generate M2e-specific memory cells and protect against influenza A infection (Abstract).
However, Eliasson does not teach a scFv that specifically binds to a surface marker on antigen presenting cells, as in claim 48, including dendritic cells, as in claim 51, or conventional type 1 dendritic cells, as in claim 52.
Regarding claim 48 and 51-52, Chen teaches a DNA vaccine encoding the Hc domain of botulinum neurotoxin serotype A (AHc) (i.e., a bacterial exotoxin) fused with scDEC, a single-chain Fv antibody (scFv) that is specific to DEC205, a surface marker on dendritic cells (Abstract), including conventional type I dendritic cells. Chen also teaches that DCs play a critical role in priming antigen-specific immune responses and that the DC-targeted DNA vaccine induced strong humoral immune responses and induced more DC maturation than a non-DC-targeted vaccine, which may be helpful for boosting the immune response (Abstract).
Regarding claim 56, Chen teaches a plasmid (i.e., an expression vector) comprising the nucleotide sequence encoding AHc and scDEC (section 2.1).
Regarding claim 57, Chen teaches that 293Ft cells were transfected with the plasmids comprising the nucleotide sequence encoding AHc and scDEC (i.e., cells containing the nucleotide sequence encoding AHc and scDEC) (section 2.2).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to combine the nucleotide sequence encoding the fusion protein comprising CTA1-DD and M2e taught by Eliasson with the nucleotide sequence encoding the scDEC antibody targeting DEC205 on dendritic cells taught by Chen, thereby arriving at the invention of claims 48-52 and 54-57. The person of ordinary skill in the art would have been motivated to make the modification because Chen teaches that the DC-targeted vaccine induced stronger immunity compared to the non-targeted vaccine. Thus, one of ordinary skill in the art would believe that targeting the fusion protein of Eliasson to DCs would boost the immune response to the M2e influenza antigen by targeting DCs to prime the M2e-specific immune response, as is taught by Chen, while maintaining the ability to target B-cells due to the DD domain. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because the DNA vaccine of Chen demonstrates that scDEC can be fused with bacterial exotoxin subunits in a fusion protein, and one of ordinary skill in the art would believe that combining modifying the CTA1-M2e-DD fusion protein of Eliasson to target dendritic cells would produce an immune response at least as well as that taught in Eliasson, based on the teachings of Chen regarding DCs and their role in the immune response. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., nucleotide sequences encoding CTA1, scFv targeting dendritic cells, and M2e) were known in the art. In addition, combining these elements yields a composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
Applicant argues (Remarks, pg. 6) that Chen does not correct the deficiencies of Eliasson because Chen does not teach or suggest an enzymatically active bacterial exotoxin.
This argument has been fully considered but is not persuasive. As set forth in the 103 rejection above, Chen is not relied upon to teach or suggest an enzymatically active bacterial exotoxin because Eliasson teaches an enzymatically active CTA1.
Applicant argues (Remarks, pg. 6-7) that because the CTA1-DD fusion protein of Eliasson binds to B-cells and the scFv of Chen targets dendritic cells, one of ordinary skill in the art would not have been motivated to modify the construct of Eliasson to target dendritic cells.
This argument has been fully considered but is not persuasive. This rejection is not persuasive for the reasons set forth in the amended 103 rejection above (see, specifically, para. 14).
Applicant argues (Remarks, pg. 7-8) that the unexpected results taught in the instant specification overcome any prima facie case of obviousness and points to Examples 2, 5, and 6.
This argument has been fully considered but is not persuasive. Regarding the allegation of unexpected results, it is noted that the instant specification does not allege that the results of Examples 2, 5, and 6 are unexpected (spec., pg. 57-58 and 60-61). Furthermore, the data discussed in Examples 2, 5, and 6 only compares two fusion proteins each (CTA1-CD103 and CTA1-DD, CTA1-3M2e-CD103 and CTA1-3M2e-DD, and CTA1-SIINFEKL-CD103 and CTA1-SIINFEKL-DD, for Examples 2, 5, and 6, respectively). This data is not commensurate in scope with the invention of claim 48, which encompasses a nucleotide sequence encoding any enzymatically active bacterial exotoxin and a nucleotide sequence encoding an scFv that specifically binds to any surface marker on any antigen presenting cell. MPEP 716.02(d) states (emphasis added): “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’ In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)” Therefore, the data presented in Examples 2, 5, and 6 is not sufficient to show unexpected results across the full scope of claim 48. Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
Claims 48, 51-53, and 56-57 remain rejected under 35 U.S.C. 103 as being unpatentable over Hadley (US 2011/0142860 A1).
Regarding claims 48, Hadley teaches an anti-CD103 antibody (i.e., an antibody that specifically binds to a surface marker on an antigen presenting cell) conjugated to a lethal compound (Abstract and para. 4). Hadley teaches that the anti-CD103 antibody may be a single chain variable fragment (scFv) (para. 34) and that the lethal compound may be shigella neurotoxin, botulism toxin, diphtheria toxin, tetanus toxin, or cholera toxin (i.e., bacterial exotoxins) (para. 66). Hadley also teaches isolated nucleic acids encoding the antibody or binding agents (e.g., bacterial exotoxins) (para. 55).
Regarding claims 51-53, Hadley teaches that the antibody binds CD103 (Abstract and para. 4), which is present on conventional type 1 dendritic cells (cDC1s).
Regarding claim 56, Hadley teaches that the isolated nucleic acid encoding the conjugate may be in a vector (para. 55).
Regarding claim 57, Hadley teaches that the isolated nucleic acid encoding the conjugate may be maintained in recombinant host cells (para. 55).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the nucleic acid encoding the anti-CD103 antibody and lethal compound conjugate by using a scFv as the anti-CD103 antibody and a bacterial exotoxin as the lethal compound, as taught by Hadley, to arrive at the invention of claims 48, 51-53, and 56-57. The person of ordinary skill in the art would have been motivated to make the modification because Hadley teaches scFvs and bacterial exotoxins as specific components that may be used in their generic antibody-lethal-compound conjugate structure. The person of ordinary skill in the art would have had a reasonable expectation of success because methods of making scFvs, toxins, and antibody conjugates are well known in the art. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., anti-CD103 scFv and bacterial exotoxin) were known in the art. In addition, combining these elements yields a composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
Applicant argues (Remarks, pg. 8) that one of ordinary skill in the art would not have been motivated to modify Hadley in the manner set forth in the NFOA and that there would have been no reasonable expectation of success because the teachings of Hadley are directed to immune suppression, whereas the instant invention is directed towards enhancing an immune response.
This argument has been fully considered but is not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., enhanced immune response) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As is set forth in the 103 rejection above, the motivation to modify the fusion protein of Hadley is not based on the effect of the fusion protein on the immune system, but instead because Hadley teaches that bacterial exotoxins may be used as the “lethal” compound in their antibody conjugate. The standard for a reasonable expectation of success in this case is not that one would reasonably expect an enhanced immune response, but that one would expect to successfully make the claimed composition, as discussed in the 103 above and thus the motivation to make and use such nucleotide sequence already exists and formulating said nucleotide sequence is predictable.
New Rejection(s)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 102
Claims 48, 51, and 56-57 are newly rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (2007, Protein Expr. Purif.; herein “Wang”).
Regarding claims 48, 51, and 56, Wang teaches a plasmid encoding a humanized anti-CD25 scFv gene (which targets CD25 markers in the surface of dendritic cells) fused to a modified but active Pseudomonas exotoxin, PE38KDELKQK gene (pg. 141, right col., para. 2).
Regarding claim 57, Wang teaches that the plasmid encoding the CD25-PE38KDELKQK fusion gene (pET32a-(CD25-PE38KDELKQK)) was expressed in E. coli BL21(DE3) (pg. 141, right col., para. 3).
Conclusion
No claim is 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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 9-5 ET.
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/BAILEY M MORGAN/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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