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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/8/2026 has been entered.
Claims 31 and 36-40 are pending in the instant application.
Priority
This application is a 371 of PCT/EP2020/059272, filed on 4/1/2020 which claims priority to the European applications EP19305535.7 filed on 4/26/2019 and on EP19305434.3 filed on 4/2/2019.
Claim Rejections – 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 40 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 40
Claim 40 is drawn to the protein or peptide antigen (or nucleic acid encoding such) comprising the protein or peptide antigen of parent claim 31. By virtue of the parent claim using language such as “said immune checkpoint is selected from the group consisting of PD-L1, …” usage of the word “comprising” in the dependent claim expands the scope of the parent to encompass subject matter other than the proteins and fragments of claim 40, and expands its scope to fusion protein comprising those proteins and fragments. As a result, this claim 40 represents an expansion of scope over parent claim 31.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections – 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 31 and 36-40 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
all claims
Claims 31 and 36-40 are drawn to anti-cancer prophylactics comprising the full-length or antigenic fragments of PD-L1, PD-1, PD-L2, CTLA-4, VISTA, TIM-3, LAG-3, GITR, IDO, KIR2D, A2AR, B7-H3, B7-H4, TIGIT, BTLA, IL6, IL10 and TGFβ; or a nucleic acid encoding thereof, wherein applicant has failed to meet the written description of this genus. In order to meet the written description requirement, applicant must supply (1) the conserved structure responsible for the function of being an anti-cancer prophylactic; or (2) supply a representative number of species allowing one of skill in the art to envisage the other members of the genus.
Regarding (1), Applicant has specified the antigen source (e.g. PD-1, but has not described which peptides of these proteins are antigenic. The discovery of antigenic peptides of a given protein is a highly unpredictable process. For example, in order to arrive at a handful of antigenic peptides of PD-1, Kaumaya (doi: 10.1080/2162402X.2020.1818437) first performed several rounds of computational screening to identify potential candidates (pg 2, col 2, para 2), of these candidates, only two candidates (residues 45-64 and 92-110) elicited high levels of anti-peptide antibodies, whereas one (residues 73-90) produced little reactive antibodies, and one (residues 32-50) was similar to control (pg 5, col 1, para 1). And in that example, in order to reach clinically relevant immunoreactive titers, the peptides were tethered to measles virus protein (MVF) (pg 11, col 1, para 3) and co-injected with the adjuvant, Montanide (abstract). Similarly, Iverson (doi: 10.1158/1078-0432.CCR-13-1560) teaches the development of an antigenic IDO peptide (of sequence ALLEIASCL) that is also formulated with adjuvant Montanide and combined with a TLR7 agonist, Iniquimod, as being effective for treating non-small cell lung cancer (pg 227, col 2, para 1; abstract). Repeating the pattern, Perez-Penco (doi: 10.1136/jitc-2022-005491) teaches computationally identifying antigenic peptides candidates of TGFβ (pg 2, col 2, para 3), followed by identification of which were actually antigenic via injection of the candidates into mice (co-injected adjuvant Montanide) (pg 5; Fig 1), followed by injecting a mixture of all the candidates to see if they treat pancreatic ductal adenocarcinoma (PDAC) (pg 6; pg 3, col 1, para 2). The candidate antigenic peptides produced variable antigenic responses as shown in Fig 1C below that could not be anticipated a priori.
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The mixture of candidate peptides when combined with the adjuvant Montanide was indeed, effective in treating PDAC (pg 3, col 1, para 2; pg 6; abstract).
Furthermore, a search of the prior art shows that antigenic peptides of CTLA-4, VISTA, TIM-3, GITR, KIR2D, A2AR, B7-H3, B7-H4, TIGIT, BTLA, and IL10 were not identified at the time of filing. Flower (doi: 10.1016/j.it.2003.10.006) teaches that immunogenic epitopes that are recognized by T or B cells is unpredictable:
“The accurate prediction of epitopes is difficult. Looking back two decades, most predictors of T- or B-cell epitopes sought to identify peaks in properties, such as hydrophilicity, plotted over protein sequences. Whereas most B-cell epitope prediction methods still rely on finding such peaks, Deavin et al. showed how inappropriate this was for T-cells [4]. In silico T-cell epitope identification currently relies on predicting what many see as the most discriminatory step of antigen presentation: peptide binding to MHCs. However, this is a necessary, but not sufficient, condition for epitope recognition. The mechanisms by which antigens are reduced to peptides bound by MHCs or how certain peptide–MHC (pMHC) complexes are recognized, whereas others are not, are both issues replete with unanswered questions.” (pg 667, col 2, para 2).
Lacking any specific antigenic peptides, applicant has also has failed to describe an adjuvant necessary to stimulate the immune system (e.g. tethering PD-1 to measles virus peptide of SEQ ID NO: 6 toxin as described in US11684660 [U.S. equivalent of applicant supplied example of WO2018183488]). In order to meet the written description of the invention being a prophylactic it must by necessity comprise some specific immune-stimulating structure which is notably absent in the claims.
Regarding (2), Applicant did not disclose a single species with the purported properties of (i) being an antigenic peptide of PD-L1, PD-1, PD-L2, CTLA-4, VISTA, TIM-3, LAG-3, GITR, IDO, KIR2D, A2AR, B7-H3, B7-H4, TIGIT, BTLA, IL6, IL10 and TGFβ, and (ii) possessing the function of being an anti-cancer prophylactic.
The burden is on Applicant to describe the invention with sufficient detail so that a practitioner can use it accordingly. MPEP §2163(II)(3) states:
“An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004).”
If Applicant is relying on the prior art to disclose the both the material composition of the invention and the verification that it possesses the capacity to be a prophylactic necessary to meet the written description, then Applicant cannot rightfully claim inventorship.
Relevant Prior Art
See Finn (doi: 10.1038/nri1150) who describes the challenges in developing anti-cancer vaccines and prophylactics, such as choosing the right adjuvant (pg 631, col 2, para 4), generating a specific immune response (pg 632, col 1, para 3), and avoiding autoimmunity (pg 631, col 2, para 2; pg 638, col 2, para 2). Finn describes these vaccines comprise antigenic peptides of viruses (e.g. HPV and HBV; pg 637) or antigenic peptides of tumor associated antigens (TAAs) such as HER2, MUC1, and CEA (pg 638-639).
Relevant Posterior Art
Applicant supplied the review article by Anderson (doi: 10.1007/s00281-022-00966-0) who teaches anti-cancer vaccines that target Tumor Microenvironment Antigens (TMAs) as opposed to Tumor Associated Antigens (TAAs). Exemplary TMAs are typically proteins expressed by regulatory T cells (and also tumor cells) that induce immunosuppression such as IDO and PD-L1, and TGFβ (Table 1). Note that Anderson does not teach administering the composition to individuals with pre-malignant, non-tumorous lesions. Notably, the reference of Anderson was published after the priority date of the instant Application, but does not acknowledge the existence of antigenic peptides of CTLA-4, VISTA, TIM-3, GITR, KIR2D, A2AR, B7-H3, B7-H4, TIGIT, BTLA, and IL10.
Response to Arguments
Applicant's arguments filed 1/8/2026 have been fully considered but they are not persuasive.
112(a); pg 5, para 1
Applicant argues the amendments specifying the invention being a “protein or peptide antigen” wherein the protein or peptide antigen is an immune checkpoint or suppressive cytokine satisfies the written description requirement. Applicant reiterates that the invention is the prophylactic treatment of the disease and is not drawn to the identity of the material that produces that effect. Applicant argues that any material that is an immune checkpoint or suppressive cytokine can be used as a prophylactic.
For the reasons described in detail above, Examiner still disagrees that the written description has been satisfied because (i) one of skill in the art would not be able to envisage antigenic peptides of the listed proteins, (ii) nor do the corresponding full-length proteins exhibit a prophylactic effect on their own. Regarding (i) a search of the prior art shows that no one has identified antigenic peptides of CTLA-4, VISTA, TIM-3, GITR, KIR2D, A2AR, B7-H3, B7-H4, TIGIT, BTLA, and IL10 at the time of filing. Regarding (ii), applicant is asserting that administration of natively occurring, full-length proteins can function as a prophylactic for treating cancer in the absence of an adjuvant. For example, if PD-L1 was an anti-cancer prophylactic, then no individual would succumb to cancer because their body is already naturally producing the claimed prophylactic.
Finally, applicant is claiming the genera of molecules function as an anti-cancer prophylactic without supplying any data in support of that assertion. In short, applicant has not described what (a) parts of the peptides are antigenic, and (b) of the selected proteins and peptides, applicant has not shown which of these produce a prophylactic response in subjects with pre-malignant dysplasia’s. As a result of these deficiencies, one of skill in the art would not be able to identify effective anti-cancer prophylactics given the supplied description.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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