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 .
Election/Restrictions
Applicant’s election without traverse of Group I, corresponding to claims 1 – 10
in the reply filed on 04/02/2026 is acknowledged.
Claims 11 – 18 are withdrawn from further consideration pursuant to 37
CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or
linking claim.
Claims 1 – 10 are under examination.
Priority
This application claims priority to US provisional application 63/422093, filed on November 03, 2022. This application also claims priority to KR application KR10-2022-1058440, filed on November 23, 2022.
Claim Rejections - 35 USC § 112 - Indefiniteness
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.
Claims 4 and 11 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.
Claims 4 and 11 recite the phrase “has an amino acid sequence set forth as SEQ ID NO…” and “having a nucleotide sequence of SEQ ID NO…”. It is not clear whether the Applicants intend this limitation to read on only the full sequence, a partial sequence, or at least the full sequence. For purposes of compact prosecution and applying prior art, claims 4 and 11 were interpreted herein as “comprising the amino acid sequences of SEQ ID NO…” and “comprising the nucleotide sequence of SEQ ID NO…” respectively.
Claim Rejections - 35 USC § 112- Scope of Enablement
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 1 - 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for inducing an immune response against RSV infection using a vaccine, does not reasonably provide enablement for preventing RSV infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
• (A) The breadth of the claims;
• (B) The nature of the invention;
• (C) The state of the prior art;
• (D) The level of one of ordinary skill;
• (E) The level of predictability in the art;
• (F) The amount of direction provided by the inventor;
• (G) The existence of working examples; and
• (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The level of skill in the art is high and would include, e.g., Ph.D. level scientists.
Here, the instant claims are broadly drawn to a method for preventing an RSV infection using a liposomal vaccine comprising a RSV antigen, MPLA, and/or CoPoP. In regard for prevention of respiratory virus infection, it is noted that the term “preventing” was interpreted in an absolute sense to mean to always keep something from happening or arising.
The claims are not enabled based on, but not limited to, not all RSV infections are prevented by the recited RSV vaccine.
The art establishes that while RSV vaccines are effective at reducing the risk of RSV infections, they are not 100% effective at preventing RSV infections (Kelleher et al, Ther Adv Vaccines Immunother, 2025, hereinafter, “Kelleher”). Kelleher evidences that multiple vaccines can reduce the risk of RSV-associated lower respiratory tract illness for different age groups, but that they are unable to prevent 100% of infections (Table 2). Furthermore, Wroblewski et al (Annals of Pharmacotherapy, 2024, hereinafter, “Wroblewski”) evidences that Arexvy, a liposomal RSV vaccine comprising an RSV antigen and MPLA, does not prevent 100% of infections (Section: Data Synthesis, Table 1). Of note, while the publication dates of Kelleher and Wroblewski are after the effective filing date of the application, the evidence establishes that at the time of the instant application, and still is, no known vaccine that prevents all RSV infections. Together with the evidence discussed above, an RSV vaccine would not predictably prevent all RSV infections.
The specification only exemplifies and reduces to practice preventing RSV infection in some cases at certain doses and formulations (Figure 11). However, the specification offers no reasonable direction or working example for the use of a liposomal vaccine that satisfies the limitations of claim 1 prevent all RSV infections. For example, Figure 12 shows an increased lung injury score depending on the formulation used, indicating a non-total prevention of RSV infection.
In view of the foregoing, a vast quantity of experimentation, including expansive clinical trials, would be needed to use the invention based on the content of the disclosure.
Taken together, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Isaacs et al (Vaccines, 2021, hereinafter, “Isaacs”). For purposes of compact prosecution, prior art is applied to the extent that claims are enabled for inducing an immune response against RSV infections using a vaccine but not for the absolute prevention of an RSV infection (See 35 USC § 112- Scope of Enablement rejection above).
Isaacs discloses the routine optimization of different antigen and adjuvant combinations towards identifying an ideal humoral responses (Abstract). Moreover, Isaacs discloses the use of intramuscular inoculation of an RSV F protein subunit vaccine injected with liposomes and oil-in-water emulsion of monophosphoryl lipid A (MPLA) and QS21 (Abstract). Isaacs also discloses that subunit vaccines exhibit favorable safety and immunogenicity profiles that can be designed to mimic native antigen structures and that pairing the antigen with adjuvants elicit more robust humoral responses (Abstract).
Regarding claims 1, 2, and 9, Isaacs discloses a vaccine composition comprised of liposomes, an RSV antigen, MPLA, and QS-21 (Introduction ¶3, Section: 2.2 Adjuvant formulation and Mouse Immunizations ¶1).
Accordingly, Isaacs anticipates the claimed invention.
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 3, 6, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Isaacs as applied to claims 1, 2, and 9 above, and further in view of Kwong et al (US20160046675A1, hereinafter, “Kwang”) and Song et al (US20150225482A1, hereinafter, “Song”).
As discussed above, claims 1, 2, and 9 were anticipated by Isaacs.
The reference does not disclose the RSV F antigen having a sequence of SEQ ID NO: 1or the RSV F antigen comprising a poly-histidine tag (His tag).
However, Kwang teaches RSV antigens including RSV F protein stabilized in a prefusion conformation (Abstract). Kwang also teaches methods of producing the antigen and generating an immune response in a subject using RSV F protein antigens (Abstract).
Song teaches optimized heavy chain and light chain signal peptides that enhances antibody secretion from cells (Abstract). Song teaches methods of determining signal peptides that are particularly useful for eliciting an immune response (Abstract). Furthermore, Song teaches combining the signal peptides in fusion proteins to induce immune response (¶0103, 0142).
Regarding claims 3, 6, and 7 Kwang teaches an RSV F antigen sequence comprising a 99.6% sequence identity with SEQ ID NO: 1, including a 6 histidine his tag at the N terminus of the antigen (reproduced below, Qy is SEQ ID NO: 1, Db is Kwang).
[AltContent: textbox ([img-media_image1.png]
[img-media_image2.png])]Kwang does not teach the initial 19 amino acids of SEQ ID NO: 1.
[AltContent: textbox ([img-media_image3.png])]However, regarding claims 3, 6, and 7, Song teaches 100% sequence similarity to the initial 19 amino acids of SEQ ID NO: 1 (reproduced below, Sequence1 is SEQ ID NO:1, Sequence2 is Song). Song also teaches that this sequence is an optimized heavy chain signal peptide for antibody secretion that can be fused to other proteins (¶0002, 0074, 0075).
Isaacs, Kwang, and Song are considered to be analogous to the claim invention because they aim to elicit immune response in a subject. Isaacs discloses a vaccine composition comprised of liposomes, an RSV antigen, MPLA, and QS-21 (Introduction ¶3, Section: 2.2 Adjuvant formulation and Mouse Immunizations ¶1). Kwang teaches an RSV F antigen sequence comprising a 99.6% sequence identity with SEQ ID NO: 1, including a 6 histidine his tag at the N terminus of the antigen (see above). While the sequence taught by Kwang is not 100% identical to SEQ ID NO: 1, it does encode an RSV F antigen and therefore covers the limitations of claim 3. Song teaches 100% sequence similarity to the initial 19 amino acids of SEQ ID NO: 1 (see above).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to fuse the heavy chain signal peptide, as taught by Song, to the RSV antigen taught by Kwang, in a composition comprising a liposome, MPLA, and QS-21, as disclosed by Isaacs, because doing so cause an optimized immune response to RSV antigen presentation within a subject. One of ordinary skill in the art would have had a reasonable expectation of success in using a fusion protein comprising an optimized signal peptide and RSV antigen in a liposomal formulation comprising MPLA and QS-21 given that RSV antigen selections that increase humoral responses in liposomal formulations is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 5 is rejected under 35 U.S.C. 103 over Isaacs as applied to claims 1, 2, and 9 above, and further in view of Lovell et al (US20180085473A1, hereinafter, “Lovell”) and Ji et al (Metabolic Engineering, 2019, hereinafter, “Ji”).
As discussed above, claims 1, 2, and 9 above were anticipated by the teachings of Isaacs.
The references do not disclose an MPLA derived from E. coli, cholesterol, and CoPoP.
However, Lovell teaches the use of CoPoP and His tags for the use of cargo delivery or delivery of presentation molecules (Summary of disclosure, Figure 1 - reproduced below). Lovell teaches that the combination of CoPoP and his tags can be combined with liposomes as vaccine formulations (Figure 6, Examples 2 and 3). Additionally, Lovell teaches the trial of liposomal vaccine comprised of CoPop and his tagged antigens with different adjuvants when testing immunogenic responses towards HIV (¶0017, Figure 6).
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Ji teaches MPLA are commonly used as an adjuvant in therapeutics but are expensive and laborious to produce (Abstract). Ji teaches a method of generating MPLA using E. coli for in situ production (Abstract). Ji also teaches that the MPLA purified from the method (EcML) stimulated the mouse immune system at levels comparable to commercially available MPLA but at reduced manufacturing time and cost (Abstract).
Regarding claim 5, Ji teaches EcML and provide motivation to use EcML in vaccines (Conclusion). As discussed above, Lovell teaches the use of CoPoP in liposomal formulations. Furthermore, Lovell teaches a composition of liposomes with CoPop, MPLA, another phospholipid, and cholesterol (Table 2, Figure 9).
Isaacs, Ji, and Lovell are considered to be analogous to the claim invention because they aim to elicit immune response in a subject. Isaacs discloses a vaccine composition comprised of liposomes, an RSV antigen, MPLA, and QS-21 (Introduction ¶3, Section: 2.2 Adjuvant formulation and Mouse Immunizations ¶1). Ji teaches the MPLA can be EcML (Figure 2). Lovell teaches a CoPoP, his tagged antigen liposome (Figure 1).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to use the MPLA, EcML, as taught by Ji, in a composition comprising a liposome, MPLA, QS-21, CoPoP, cholesterol, and another lipid as taught by Isaacs and Lovell, because doing so cause an optimized immune response to RSV antigen presentation within a subject at a reduced cost. One of ordinary skill in the art would have had a reasonable expectation of success in using a fusion protein comprising an optimized signal peptide and RSV antigen in a liposomal formulation comprising MPLA, QS-21, CoPoP, cholesterol, and another lipid given that this formulation increases humoral responses in liposomal formulations while being cost effective is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 8 is rejected under 35 U.S.C. 103 over Isaacs, Kwang, and Song as applied to claim 1 – 3, 6, 7, and 9 above, and further in view of Lovell.
As discussed above, claims 1 – 3, 6, 7, and 9 were anticipated by the teachings of Isaacs and/or rendered prima facie obvious in view of Kwang and Song.
The references do not disclose a liposomal vaccine formulation comprised of cobalt porphyrin-phospholipid (CoPoP) or the structural features of the liposomal vaccine formulation.
However, regarding claim 8, Lovell teaches liposomes where a portion of the his-tag is present in a hydrophobic portion of the liposome and is coordinates to the cobalt metal core of CoPoP (¶0011, Figure 1, reproduced above).
Isaacs, Kwang, Song, and Lovell are considered to be analogous to the claim invention because they aim to elicit immune response in a subject. Isaacs discloses a vaccine composition comprised of liposomes, an RSV antigen, MPLA, and QS-21 (Introduction ¶3, Section: 2.2 Adjuvant formulation and Mouse Immunizations ¶1). Kwang teaches an RSV F antigen sequence comprising a 99.6% sequence identity with SEQ ID NO: 1, including a 6 histidine his tag at the N terminus of the antigen (see above). Song teaches 100% sequence similarity to the initial 19 amino acids of SEQ ID NO: 1 (see above). Lovell teaches a CoPoP, his tagged antigen liposome (Figure 1).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to fuse the heavy chain signal peptide, as taught by Song, to the RSV antigen with his tag taught by Kwang, in a composition comprising a liposome, MPLA, QS-21, and CoPop, as taught by Isaacs and Lovell, because doing so cause an optimized immune response to RSV antigen presentation within a subject. One of ordinary skill in the art would have had a reasonable expectation of success in using a fusion protein comprising an optimized signal peptide and RSV antigen in a liposomal formulation comprising CoPoP, MPLA, and QS-21 given that RSV antigen selections that increase humoral responses in liposomal formulations is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Isaacs as applied to claims 1, 2, and 9 above, and further in view of Pfizer (Press release, August 2022, hereinafter, “Pfizer”).
As discussed above, claims 1, 2, and 9 were anticipated by Isaacs.
The reference does not disclose vaccine comprised of two RSV F antigens.
However, regarding claim 10, Pfizer teaches a bivalent vaccine comprised of two RSV F antigens (¶1). Pfizer teaches the preliminary results of a phase 3 clinical trials using this bivalent vaccine which improves protection against RSV (¶2). Pfizer also teaches bivalent vaccines can be used in pregnant individuals as well as susceptible older adults (¶5, 9, and 10).
Isaacs and Pfizer are considered to be analogous to the claim invention because they aim to elicit immune response against RSV in a subject. Isaacs discloses a vaccine composition comprised of liposomes, an RSV antigen, MPLA, and QS-21 (Introduction ¶3, Section: 2.2 Adjuvant formulation and Mouse Immunizations ¶1). Pfizer teaches RSV vaccines can include two RSV F antigens (¶1).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to include two RSV F protein antigens, as taught by Pfizer, in a composition comprising a liposome, MPLA, and QS-21 as taught by Isaacs, because doing so cause an optimized, broad, improved protection against RSV within a subject. One of ordinary skill in the art would have had a reasonable expectation of success in using multiple RSV F protein antigens in a liposomal formulation comprising MPLA and QS-21 given that this formulation increases broad humoral responses is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Bian et al (Front Immunol, 2022)
Joshi et al (Expert opinion on drug delivery, 2019)
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANYAL HASSAN ALAM/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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