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 .
2. Applicant’s amendment filed on 07/08/2026 is acknowledged.
3. Claims 1-7, 9-12, 15-17, 19, 24, 26, 29-31, 35 and 37 are pending.
4. Claims 29-31, 35 and 37 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group and claims 15-17 and 19 are withdrawn as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/20/2026.
5. Claims 1-7, 9-12, 24 and 26 are under consideration as they read on “a vaccine comprising DSPE as the lipid, PEG2x as the linker, and MD39 trimer as the immunogen, wherein the linker is positioned between the lipid and the immunogen.”
6. Applicant’s IDS document filed on 07/08/2026 have been considered.
7. The following rejections are maintained in view of Applicant’s response filed on 07/08/2026.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 1-7, 9-12, 24 and 26 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not reasonably provide enablement for: a vaccine comprising an amphiphilic conjugate, wherein the amphiphilic conjugate comprises an immunogen operably linked to an albumin-binding lipid, and wherein the vaccine is suitable for transmucosal administration to induce a humoral immune response of claim 1; wherein the transmucosal administration is intranasal administration of claim 2; wherein the immunogen is a protein antigen having a molecular weight between about 10 kDa and about 500 kDa of claim 3; wherein the immunogen comprises a protein antigen selected from the group consisting of a human immunodeficiency virus (HIV) antigen, a SARS-CoV-2 antigen, an influenza antigen, a rotavirus antigen, a cytomegalovirus (CMV) antigen, an Epstein-Barr virus (EBV) antigen, a respiratory syncytial virus (RSV) antigen, and a cholera antigen of claim 4; wherein the immunogen comprises a monomer antigen or trimer antigen of claim 5; wherein the immunogen comprises an antigenic peptide of claim 6; wherein the albumin-binding lipid is selected from the group consisting of a cholesterol, a monoacyl lipid, and a diacyl lipid of claim 7;
wherein the albumin-binding lipid is 1 ,2-distearoyl-sn-glycero-3 phosphoethanolamine (DSPE) of claim 9; wherein the immunogen is operably linked to the albumin-binding lipid via a first linker of claim 10; wherein the first linker is selected from the group consisting of a hydrophilic polymer, a string of hydrophilic amino acids, polysaccharides, oligonucleotides, or a combination thereof of claim 11; wherein the first linker comprises a polyethylene glycol (PEG) linker of claim 12; further comprising an adjuvant of claim 24; and wherein transmucosal administration of the vaccine elicits or enhances production of antibodies that bind to the immunogen of claim 26.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and or use the invention commensurate in scope with the claims. The specification disclosure does not enable one skilled in the art to practice the invention without an undue amount of experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
At issue is whether or not the claimed compositions could be used as vaccines. Vaccines are used to prevent specific diseases caused by a specific agent. The claims do not recite any disease to be prevented by the use of the claimed vaccines. At a minimum, claims directed to using vaccines must be directed to specifically preventing a particular disease. A “vaccine” to treat an unspecified disease is not enabled as the vaccine composition would be unsuccessfully used to treat any other disease or disorder than the one that it is formulated to prevent. One of ordinary skill in the art would be required to perform undue experimentation to make and use a vaccine formulated for preventing disorder X to prevent disorder Y.
Furthermore, the specification does not provide sufficient guidance on how to sufficiently any disease (vaccination) by administering the claimed compounds. The first criterion in judging a vaccine is the level of antibody (humoral immune response) before and after immunization. The success of the vaccination is judged by the extent of increase in the level of antigen - specific antibody. The second criterion for a vaccine is its ability to stimulate memory T lymphocytes (cell-mediated immune response) (See Kuby; PTO-892; Reference U). As such one of ordinary skill in the art would be required to perform undue experimentation to make and use the genus of vaccines encompassed for pharmaceutical use in preventing disease.
The specification fails to provide guidance as to how to prevent (100% prevention) any disease using any of the recited agents. The art is highly unpredictable as to what will be a therapy for HIV for example, so it would require an undue amount of experimentation for one of ordinary skill in the art to practice the claimed invention commensurate in the scope with the claims. The invention may encompass pharmaceutical compositions which treat HIV for example, but the specification does not disclose how to totally prevent HIV for example using a “vaccine” composition.
As evidenced by the HIVinfo.NIH.gov website on 04/04/2026, no FDA-approved preventive HIV vaccines currently exist (PTO-892; Reference V). As such, the specification is not enabled for any HIV vaccine of any kind.
The specification is not enabled for any vaccine which comprises “an immunogen” of claim 1; an immunogen “which is a protein wherein the immunogen is a protein antigen having a molecular weight between about 10 kDa and about 500 kDa” of claim 3; an immunogen which “comprises a protein antigen selected from the group consisting of a human immunodeficiency virus (HIV) antigen, a SARS-CoV-2 antigen, an influenza antigen, a rotavirus antigen, a cytomegalovirus (CMV) antigen, an Epstein-Barr virus (EBV) antigen, a respiratory syncytial virus (RSV) antigen, and a cholera antigen” of claim 4; “wherein the immunogen comprises a monomer antigen or trimer antigen” of claim 5; and“wherein the immunogen comprises an antigenic peptide” of claim 6. The specification is not enabled any of these immunogens “wherein transmucosal administration of the vaccine elicits or enhances production of antibodies that bind to the immunogen” of claim 26. One of ordinary skill in the art would be required to perform undue experimentation to make and use the invention commensurate in scope with the claims.
Since no in vivo studies were used as model system to prevent any disorder it is not clear that reliance on the in vitro data accurately reflects the relative animal efficacy of the claimed therapeutic strategy. The specification does not adequately teach how to effectively treat any disorders or reach any therapeutic endpoint in animals by administrating the vaccine, much less any disorder as encompassed by the instant claims. The specification does not teach how to extrapolate data obtained from the in vitro studies to the development of effective in vivo animal therapeutic treatment, commensurate in scope with the claimed invention. There must be a rigorous correlation of biological activity between the disclosed in vitro activity and an in vivo effectiveness to establish a method of preventing disease using a “vaccine”.
Although, the specification describes in vitro experiments, there is no correlation on this record between the in vitro studies and the preventing HIV for example in currently available form for humans or animals. It is not enough to rely on in vitro studies where, as here, a person having ordinary skill in the art has no basis for perceiving those studies as constituting recognized screening procedures with clear relevance to efficacy in humans or animals (emphasis added). Ex parte Maas, 9 USPQ2d 1746
In view of the absence of a specific and detailed description in Applicant's specification of how to effectively use the genus of “vaccine” compositions claimed, absence of working examples providing evidence which is reasonably predictive that the genus of claimed agents are effective for in vivo use for prevention of disease, and the lack of predictability in the art at the time the invention was made, an undue amount of experimentation would be required to practice the claimed vaccine compositions with a reasonable expectation of success.
Substantiating evidence may be in the form of animal tests, which constitute recognizedscreening procedures with clear relevance to efficacy in humans. See Ex parte Krepelka, 231USPQ 746 (Board of Patent Appeals and Interferences 1986) and cases cited therein. Ex parteMaas, 9 USPQ2d 1746.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
Applicant’s arguments filed on 07/08/2026 have been fully considered, but are not found persuasive.
Applicant argues:
Claims 1-7, 9-12, 24, and 26 are rejected under 35 U.S.C. § 112(a) as allegedly failing to comply with the enablement requirement. The Examiner alleges that the specification does not enable one skilled in the art to make and use the claimed vaccine compositions without undue experimentation, asserting that vaccines must be directed to preventing a specific disease with 100% prevention and that no FDA-approved HIV vaccines currently exist. Applicant respectfully traverses this rejection.
Applicant submits that the Examiner has conflated the enablement standard with requirements for complete disease prevention and FDA approval, neither of which is the legal standard for enablement under 35 U.S.C. § 112(a). The enablement requirement asks whether one skilled in the art can make and use the claimed invention without undue experimentation, not whether the invention achieves 100% therapeutic efficacy or has received regulatory approval. Claim 1 recites "[a] vaccine comprising an amphiphilic conjugate, wherein the amphiphilic conjugate comprises an immunogen operably linked to an albumin-binding lipid, and wherein the vaccine is suitable for transmucosal administration to induce a humoral immune response." The claims, thus, require only that the composition be "suitable" to "induce a humoral immune response," not that it achieves complete disease prevention. This is additionally supported by the definition of the term "vaccine" in the application as published (Specification, [0103]1):
As used herein, "vaccine" refers to a composition which contains an amphiphilic conjugate as described herein, which is in a form that is capable of being administered (e.g., transmucosally or intranasally) to a subject, and which is capable of inducing a protective immune response. In embodiments, the protective immune response is sufficient to induce immunity, and/or to prevent and/or ameliorate an infection or disease, and/or to reduce at least one symptom of an infection or disease, and/or to enhance the efficacy of another dose of the amphiphilic conjugate. Upon introduction into a host, the vaccine provokes an immune response including, but not limited to, the production of antibodies and/or cytokines and/or the activation of cytotoxic T cells, antigen presenting cells, helper
In addition, the Examiner asserts that "no in vivo studies were used as model system to prevent any disorder", Office Action, page 6. Applicant respectfully traverses this rejection. Contrary to the Examiner's assertion that the specification lacks in vivo data, the specification provides extensive in vivo working examples demonstrating that the claimed amphiphilic conjugates induce humoral immune responses following intranasal administration.
For instance, Example 4 of the present specification (id., [0244]) shows the amphiphilic conjugate (amph-eOD; eOD is an HIV-derived immunogen, id. [0018]) induces superior germinal center (GC) and follicular helper T cell (Tfh) responses in nasal-associated lymphoid tissue (NALT) in mice following intranasal imunization. See also, id., Figs. 3A-3H; [0030]. Furthermore, as described in Example 5 (id., [0245]-[0248]), BALB/c mice immunized intranasally with amph-eOD conjugates exhibited enhanced IgG and IgA titers in serum, vaginal wash, and feces compared to unconjugated immunogen. See also, id., Figs. 4A- 4J, [0031].Moreover, Example 6 (id., [0250]-[0251]) demonstrates that amph-RBD conjugates (comprising immunogens derived from the SARS-CoV-2 receptor-binding domain) elicited enhanced systemic and mucosal neutralizing antibody responses in BALB/c mice following intranasal vaccination, including IgG and IgA titers in serum, vaginal wash, fecal wash, saliva, nasal wash, and bronchoalveolar lavage fluid. See also, id., Figs. 5A-5F, [0032].
Importantly, Example 7 (id., [0252]-[0253]) also provides in vivo data in non-human primates, demonstrating that intranasal immunization with amph-eOD conjugates enhanced vaccine uptake in the nasal passages and enhanced IgG and IgA responses relative to soluble protein immunization. See also, id., Figs. 6A-6E, [0033].
Finally, Example 8 (id., [0254]-[0260]) demonstrates that the amphiphilic conjugate with HIV-derived trimer immunogen (amph-MD39) elicited enhanced systemic and mucosal immune responses after intranasal immunization in mice. See also, id., Figs. 19A-19B, [0046].
Applicant respectfully submits that the specification's numerous in vivo working examples, which demonstrate that the claimed amphiphilic conjugates induce humoral immune responses upon intranasal delivery, provide robust enabling support. In view of this extensive experimental disclosure, the level of experimentation required to practice the full scope of the claims is far from "undue" under the Wands factors.
Moreover, the specification also provides detailed guidance on making the claimed amphiphilic conjugates. The specification discloses specific immunogens including eOD-GT8 (an HIV-derived immunogen), RBD (a SARS-CoV-2-derived immunogen), and MD39 trimer (an HIV envelope trimer). Id., [0018]-[0019], [0044]-[0045]. The specification discloses specific albumin-binding lipids including DSPE. Id., [0015]. The specification further discloses specific linkers including PEG2K linkers and DBCO-PEG4 linkers, along with detailed reaction schemes for preparing the amphiphilic conjugates. Id., [0016]-[0017]; Figs. 7A-7B, 17A-17B.
Lastly, the Examiner's own cited prior art undermines the assertion that the art is unpredictable. The Examiner cites Tokatlian et al., 'Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes.' Scientific Reports, volume 8, article number: 16527 (2018), as anticipating or rendering obvious the claimed vaccine compositions. Tokatlian teaches that MD39-conjugated liposomes elicit humoral responses in mice (Tokatlian, Abstract), demonstrating that the art recognized that similar vaccine compositions comprising protein immunogens conjugated to liposomes can induce antibody responses. The Examiner cannot simultaneously rely on Tokatlian to reject the claims under 35 U.S.C. § 102 and § 103 while also asserting that the specification fails to enable the claimed compositions due to unpredictability in the art.
For at least these reasons, Applicant respectfully requests that the rejection under 35 U.S.C. § 112(a) for lack of enablement be withdrawn.
It remains the Examiner’s position that the specification is not enabled for the recited vaccines. The Examiner has never argued that FDA approval is the standard for enablement for vaccines The Examiner presented evidence to show that it is well known that there are no HIV vaccines. The enablement required for a vaccine is not inducing a humoral response, contrary to Applicant’s assertion. Applicant’s own definition of the term vaccine includes prevention. It remains the Examiner’s position that there are no in vivo studies used to prevent any disorder. Humoral responses are insufficient to provide enablement for vaccines.
It also remains the Examiner’s position that the specification is not enabled for “an immunogen” of claim 1; an immunogen “which is a protein wherein the immunogen is a protein antigen having a molecular weight between about 10 kDa and about 500 kDa” of claim 3; an immunogen which “comprises a protein antigen selected from the group consisting of a human immunodeficiency virus (HIV) antigen, a SARS-CoV-2 antigen, an influenza antigen, a rotavirus antigen, a cytomegalovirus (CMV) antigen, an Epstein-Barr virus (EBV) antigen, a respiratory syncytial virus (RSV) antigen, and a cholera antigen” of claim 4; “wherein the immunogen comprises a monomer antigen or trimer antigen” of claim 5; and“ wherein the immunogen comprises an antigenic peptide” of claim 6. The specification is not enabled any of these immunogens “wherein transmucosal administration of the vaccine elicits or enhances production of antibodies that bind to the immunogen” of claim 26. One of ordinary skill in the art would be required to perform undue experimentation to make and use the invention commensurate in scope with the claims.
The rejection is maintained for reasons of record.
10. Claims 1-7, 9-12, 24 and 26 stand 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is not in possession of: a vaccine comprising an amphiphilic conjugate, wherein the amphiphilic conjugate comprises an immunogen operably linked to an albumin-binding lipid, and wherein the vaccine is suitable for transmucosal administration to induce a humoral immune response of claim 1; wherein the transmucosal administration is intranasal administration of claim 2; wherein the immunogen is a protein antigen having a molecular weight between about 10 kDa and about 500 kDa of claim 3; wherein the immunogen comprises a protein antigen selected from the group consisting of a human immunodeficiency virus (HIV) antigen, a SARS-CoV-2 antigen, an influenza antigen, a rotavirus antigen, a cytomegalovirus (CMV) antigen, an Epstein-Barr virus (EBV) antigen, a respiratory syncytial virus (RSV) antigen, and a cholera antigen of claim 4; wherein the immunogen comprises a monomer antigen or trimer antigen of claim 5; wherein the immunogen comprises an antigenic peptide of claim 6; wherein the albumin-binding lipid is selected from the group consisting of a cholesterol, a monoacyl lipid, and a diacyl lipid of claim 7; wherein the albumin-binding lipid is 1 ,2-distearoyl-sn-glycero-3 phosphoethanolamine (DSPE) of claim 9; wherein the immunogen is operably linked to the albumin-binding lipid via a first linker of claim 10; wherein the first linker is selected from the group consisting of a hydrophilic polymer, a string of hydrophilic amino acids, polysaccharides, oligonucleotides, or a combination thereof of claim 11; wherein the first linker comprises a polyethylene glycol (PEG) linker of claim 12; further comprising an adjuvant of claim 24; and wherein transmucosal administration of the vaccine elicits or enhances production of antibodies that bind to the immunogen of claim 26.
The specification has not adequately described any the structure of “an immunogen” of claim 1; an immunogen “which is a protein wherein the immunogen is a protein antigen having a molecular weight between about 10 kDa and about 500 kDa” of claim 3; an immunogen which “comprises a protein antigen selected from the group consisting of a human immunodeficiency virus (HIV) antigen, a SARS-CoV-2 antigen, an influenza antigen, a rotavirus antigen, a cytomegalovirus (CMV) antigen, an Epstein-Barr virus (EBV) antigen, a respiratory syncytial virus (RSV) antigen, and a cholera antigen” of claim 4; “wherein the immunogen comprises a monomer antigen or trimer antigen” of claim 5; and “wherein the immunogen comprises an antigenic peptide” of claim 6; and the function of being a vaccine of claim 1 and “wherein transmucosal administration of the vaccine elicits or enhances production of antibodies that bind to the immunogen” of claim 26.
Conception cannot be achieved until a representative description of the structural and functional properties of the claimed invention has occurred, regardless of the complexity or simplicity of the method.
The specification has neither demonstrated a structure function relationship nor provided a representative number of species of immunogens with the recited functions.
The specification must set forth the structural features that allow one of ordinary skill in the art to identify and produce the recited immunogens. In the instant case, definition by function does not suffice to define the genus because it is only an indication of what the immunogens do, rather than what they are.. "Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features" Ex parte Kubin (83 U.S.P.Q.2d 1410 (BPAI 2007)), at page 16. In this instant case, Applicants have not provided the requisite identifying structural features of the immunogens encompassed. "Without a correlation between structure and function, the claim does little more than define the claimed invention by function" supra, at page 17.
The specification does not provide adequate written description of the claimed invention.
The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111
(Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention.
Adequate written description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it. In the instant application, the amino acid sequence itself or isolated protein is required. See Fiers v. Revel, 25 USPQ 2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts., 18 USPQ2d 1016. In view of the aforementioned problems regarding description of the claimed invention, the specification does not provide an adequate written description of the invention claimed herein.
See The Regents of the University of California v. Eli Lilly and Company, 43 USPQ2d 1398,
1404-7 (Fed. Cir. 1997). In University of California v. Eli Lilly and Co., 39 U.S.P.Q.2d 1225
(Fed. Cir. 1995) the inventors claimed a genus of DNA species encoding insulin in different vertebrates or mammals, but had only described a single species of cDNA which encoded rat insulin. The court held that only the nucleic acids species described in the specification (i.e. nucleic acids encoding rat insulin) met the description requirement and that the inventors were not entitled to a claim encompassing a genus of nucleic acids encoding insulin from other vertebrates, mammals or humans, id. at 1240. The Federal Circuit has held that if an inventor is "unable to envision the detailed constitution of a gene so as to distinguish it from other materials.
. .conception has not been achieved until reduction to practice has occurred", Amgen, Inc. v.
Chugai Pharmaceutical Co, Ltd., 18 U.S.P.Q.2d 016 (Fed. Cir. 1991). Attention is also directed to the decision of The Regents of the University of California v. Eli Lilly and Company (CAFC,
July 1997) wherein is stated: "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Thus, as we have previously held, a cDNA is not defined or described by the mere name "cDNA," even if accompanied by the name of the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA." See
Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
As such, there is insufficient written description of the required kind of structure identifying information about the corresponding makeup of the claimed vaccine compositions comprising immunogens to demonstrate possession.
Applicant’s arguments filed on 07/08/2026 have been fully considered, but are not found persuasive.
Applicant argues:
Claims 1-7, 9-12, 24, and 26 are rejected under 35 U.S.C. § 112(a) as allegedly failing to comply with the written description requirement. The Examiner alleges that the specification has not adequately described the structure of "an immunogen" and does not demonstrate possession of the claimed vaccine compositions. Applicant respectfully traverses this rejection.
Contrary to the Examiner's allegations, the specification provides detailed structural descriptions of representative immunogens. Specifically, the specification discloses specific HIV-derived immunogens, including the MD39 trimer (Example 8) and HIV gp120 engineered outer domain-germ line-targeting immunogen 8 (eOD-GT8) (Examples 2-5, 7). The specification further discloses SARS-CoV-2-derived immunogens, including immunogens derived from the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (Example 6). In addition, the amino acid sequences of these immunogens are provided in the present specification, e.g., eOD- GT8 as SEQ ID NO: 1 in [0269], RBD as SEQ ID NO: 2 in [0270], and MD39 as SEQ ID NO: 3 in [0271]. These specific immunogens are described with sufficient structural detail to demonstrate possession.
The present specification also provides detailed guidance on the structural characteristics of the claimed immunogens. For instance, the present specification discloses that the immunogen may be a protein having a molecular weight between about 10 kDa to about 500 kDa, and provides extensive disclosure of amino acid ranges for protein antigens, [0122]-[0125]. The specification further describes that the immunogen may comprise a monomer antigen or a multimeric antigen such as a trimer antigen, [0126]-[0127].
The specification also discloses specific albumin-binding lipids including DSPE and specific linkers including PEG2K and DBCO-PEG4, [0015]-[0017]. Notably, the elected species (DSPE as the lipid, PEG2K as the linker, and MD39 trimer as the immunogen) are each specifically disclosed and characterized in the specification.
Moreover, the present specification includes detailed working examples demonstrating in vivo immunization with the claimed amphiphilic conjugates as described herein above. Furthermore, Applicant shows the synthesis and purification of the amphiphilic conjugates, as evidence in Example 8 ( [0255]) and in the Materials and Methods section ( [0269]-[0273]). These working examples demonstrate that Applicant possessed the claimed vaccine compositions and their ability to induce humoral immune responses.
For at least these reasons, Applicant respectfully requests that the rejection under 35 U.S.C. § 112(a) for lack of written description be withdrawn.
It is the Examiner’s position that the specification does not provide adequate written description for the recited immunogens.
The specification does not provide adequate written description of the claimed invention. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the ... claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention. regarding description of the claimed invention, the specification does not provide an adequate written description of the invention claimed herein. See The Regents of the University of California v. Eli Lilly and Company, 43 USPQ2d 1398, 1404-7 (Fed. Cir. 1997). In University of California v. Eli Lilly and Co., 39 U.S.P.Q.2d 1225 (Fed. Cir. 1995) the inventors claimed a genus of DNA species encoding insulin in different vertebrates or mammals, but had only described a single species of cDNA which encoded rat insulin. The court held that only the nucleic acids species described
in the specification (i.e. nucleic acids encoding rat insulin) met the description
requirement and that the inventors were not entitled to a claim encompassing a genus
of nucleic acids encoding insulin from other vertebrates, mammals or humans, id. at
1240. The Federal Circuit has held that if an inventor is "unable to envision the detailed
constitution of a gene so as to distinguish it from other materials . . . conception has not
been achieved until reduction to practice has occurred", Amgen, Inc. v. Chugai
Pharmaceutical Co, Ltd., 18 U.S.P.Q.2d 016 (Fed. Cir. 1991). Attention is also directed
to the decision of The Regents of the University of California v. Eli Lilly and Company
(CAFC, July 1997) wherein is stated: "The description requirement of the patent statute
requires a description of an invention, not an indication of a result that one might
achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369,
372-373 (Fed. Cir. 1984) (affirming rejection because the specification does "little more
than outlin[ e] goals appellants hope the claimed invention achieves and the problems
the invention will hopefully ameliorate."). Accordingly, naming a type of material
generally known to exist, in the absence of knowledge as to what that material consists
of, is not a description of that material. Thus, as we have previously held, a cDNA is not
defined or described by the mere name "cDNA," even if accompanied by the name of
the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA." See Fiers, 984
F.2d at 1171, 25 USPQ2d at 1606.
The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or U.S.C 112, I 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical
and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
A "sufficient description of a genus requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id.
"A sufficient description of a genus requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
With respect to representative number of species, see AbbVic Deutschland GmbH & Co.V. Janssen Biotech, Inc. (Fed. Cir. 2014). Also, see MPEP 2163 II(A)(3)(a))(ii):
"A representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See Abb Vie Deutschland GmbH & Co., KG V. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., Koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
In the instant case, the examples in the specification do not sufficiently represent the broad genus of recited immunogens.
Given the broadly claimed class of structures with the function of being an immunogen and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class of polypeptides encompassed by the claims, the patentee must establish "a reasonable structure-function correlation" either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. V. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163.
As such, there is insufficient written description of the required kind of structure
identifying information about the corresponding makeup of the claimed CAR antibodies to demonstrate possession.
The rejection is maintained for reasons of record.
11. 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.
12. 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.
13. Claims 1-7, 10-11, 24 and 26 stand rejected under 35 U.S.C. 102(1)(1) as being anticipated by Tokatlian et al. (PTO-892; Reference W)
Tokatlian et al. teaches covalently anchoring a stabilized HIV envelope gp140 trimer, BG505 MD39, on the surfaces of synthetic liposomes to study the effects of trimer density and vesicle stability on vaccine-elicited humoral responses in mice. (In particular, abstract).
MD39-conjugated liposomes were prepared by unilamellar liposomes comprised of phospholipid:cholesterol:DGS-NTA(Ni):MPB lipids in a 61.5:28.5:5:5 mole ratio were synthesized by lipid film rehydration and membrane extrusion using a 100 nm membrane at T > Tm(phospholipid) (DMPC = 37 °C, DPPC = 50 °C, DSPC = 60 °C), followed by post-synthesis binding of 6xHis-Cys C-terminal-modified trimer (MD39-HHHHHHC) for 1 hour at 37 °C in PBS (final concentrations 2.1 µM MD39, 3.53 mM liposomes) followed by 16–18 hr incubation at 4 °C with rotation. Non-covalent liposomes were prepared similarly without MPB lipid (phospholipid:cholesterol:DGS-NTA(Ni) lipids in a 66.5:28.5:5 mole ratio). Increasingly stabilized liposomes were prepared with 15 mole% MPB lipid and with sphingomyelin in place of cholesterol (phospholipid:sphingomyelin:DGS-NTA(Ni):MPB lipids in a 51.5:28.5:5:15 mole ratio) (In particular, page 9, whole document).
Female balb/c mice (6–10 weeks old, Jackson Laboratories) were immunized with 1 µg MD39 trimer conjugated to liposomes mixed with 0.2 U ISCOMATRIX adjuvant (CSL Ltd.) or 5 µg in-house saponin adjuvant.
Claim 2 is included in this rejection because absent evidence to the contrary the claimed MD39 liposome formulation is not incompatible with intranasal administration.
The reference teachings anticipate the claimed invention.
Applicant’s arguments filed on 07/08/2026 have been fully considered, but are not found persuasive.
Applicant argues:
Claims 1-7, 10-11, 24, and 26 are rejected under 35 U.S.C. § 102(a)(1) as allegedly being anticipated by Tokatlian et al. (Tokatlian et al., 'Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes.' Scientific Reports, volume 8, article number: 16527 (2018), "Tokatlian"). Applicant respectfully traverses this rejection.
Claim 1 recites "[a] vaccine comprising an amphiphilic conjugate, wherein the amphiphilic conjugate comprises an immunogen operably linked to an albumin-binding lipid, and wherein the vaccine is suitable for transmucosal administration to induce a humoral immune response." The claim, thus, requires a specific structural configuration: an amphiphilic conjugate in which the immunogen is operably linked to an albumin-binding lipid. Applicant submits that Tokatlian does not teach the claimed amphiphilic conjugate.
The critical distinction between the present application and Tokatlian is the use of a liposome in Tokatlian vs. the use of an amphiphilic conjugate in the present application. Tokatlian teaches anchoring of an immunogen (stabilized gp140 trimer, BG505 MD39) on the surface of synthetic liposomes via histidine-nickel (His-Ni) coordination chemistry and MPB- thiol covalent linkages, (Tokatlian, Abstract; pp. 2 and 9; See also Office Action, pp. 12-13). The liposomes of Tokatlian are multicomponent lipid vesicles comprising phospholipids (e.g., DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine)) and cholesterol or sphingomyelin (Tokatlian, pp. 8-9). These are structural lipids that form the liposome membrane, not albumin-binding lipids operably linked to the immunogen.
In contrast, the claimed amphiphilic conjugate is a distinct molecular species (e.g., comprising a protein operably linked to a lipid). As exemplified in the specification, "the general structure of the amphiphilic conjugate is L-P-C, where "L" is an albumin-binding lipid, "P" is a polar block linker, and "C" is a cargo such as an immunogen", [0109]. Thus, the present application claims a discrete molecular conjugate as opposed to a multicomponent lipid vesicle particle functionalized with protein bound to the vesicle surface as in Tokatlian.
The claimed amphiphilic conjugates operate through a fundamentally different” mechanism than the liposome delivery system of Tokatlian. As described in the specification, the claimed amphiphilic conjugates use albumin as a chaperone to traverse mucosal surfaces via FcRn interactions. See Specification, [0106]-[0108]. This albumin-mediated transmucosal delivery mechanism requires the immunogen to be conjugated to an albumin-binding lipid, which binds to endogenous albumin and enables uptake across mucosal epithelium via the neonatal Fc receptor (FcRn). Tokatlian's liposome-displayed immunogens do not possess this structural feature and do not operate through this mechanism.
The Examiner has not identified any teaching in Tokatlian of an immunogen "operably linked to an albumin-binding lipid" as recited in claim 1. Rather, Tokatlian teaches an immunogen displayed on the exterior surface of a liposome nanoparticle through surface attachment chemistry.
For at least these reasons, Applicant respectfully requests that the anticipation rejection under 35 U.S.C. § 102 be withdrawn.
It is the Examiner’s position that the term “operably linked” encompasses the covalent linkage of Tokatlian et al.
[0083] As used herein, the terms "linked", "operably linked," "fused", or "fusion", are used interchangeably. These terms refer to the joining together of two more elements or components or domains, by an appropriate means including chemical conjugation or recombinant DNA technology.
[00105] A diversity of amphiphilic conjugate structures are provided, wherein a lipophilic albumin-binding moiety, or "lipid tail" (e.g. DSPE), is linked (e.g., covalently linked) via a linker (e.g., PEG linker) to an immunogen, such as a peptide or protein antigen.
Applicant’s argument that “the liposomes of Tokatlian are multicomponent lipid vesicles comprising phospholipids (e.g., DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine)) and cholesterol or sphingomyelin (Tokatlian, pp. 8-9)” These are structural lipids that form the liposome membrane, not albumin-binding lipids operably linked to the immunogen.” is unpersuasive. Claim 7 actually recites cholesterol as an albumin binding lipid.
The specification discloses:
[0084] The term "lipid" refers to a biomolecule that is soluble in nonpolar solvents and insoluble in water. Lipids are often described as hydrophobic or amphiphilic molecules which allows them to form structures such as vesicles or membranes in aqueous environments. Lipids include fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids (including cholesterol), prenol lipids, saccharolipids, and polyketides. In some embodiments, the lipid suitable for the amphiphilic conjugates of the disclosure binds to human serum albumin under physiological conditions. In some embodiments, the lipid suitable for the amphiphilic conjugates of the disclosure inserts into a cell membrane under physiological conditions. In some embodiments, the lipid binds albumin and inserts into a cell membrane under physiological conditions. In some embodiments, the lipid is a diacyl lipid. In some embodiments, the diacyl lipid comprises more than 12 carbons. In some embodiments, the diacyl lipid comprises at least 13, at least 14, at least 15, at least 16, at least 17 or at least 18 carbons.
It is the Examiner’s position that DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), cholesterol and sphingomyelin are encompassed by the term albumin binding lipid. Applicant’s arguments about the functioning of their amphiphilic conjugate being different from the prior art are unpersuasive. The claims do not recite “the claimed amphiphilic conjugates use albumin as a chaperone to traverse mucosal surfaces via FcRn interactions. See Specification, [0106]-[0108]. This albumin-mediated transmucosal delivery mechanism requires the immunogen to be conjugated to an albumin-binding lipid, which binds to endogenous albumin and enables uptake across mucosal epithelium via the neonatal Fc receptor (FcRn).” The arguments of counsel cannot take the place of evidence in the record. In re Schulze , 145 USPQ 716, 718 (CCPA 1965). See MPEP 716.01(C). The Examiner has met the claim limitations and that is all that is required.
The rejection stands for reasons of record.
14. 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.
15. Claims 1-7, 9-12, 24 and 26 stand rejected under 35 U.S.C. 103 as being unpatentable over Tokatlian et al. (PTO-892; Reference W) in view of Wang et al. (PTO-892; Reference X).
Tokatlian et al. teaches covalently anchoring a stabilized HIV envelope gp140 trimer, BG505 MD39, on the surfaces of synthetic liposomes to study the effects of trimer density and vesicle stability on vaccine-elicited humoral responses in mice. (In particular, abstract).
MD39-conjugated liposomes were prepared by unilamellar liposomes comprised of phospholipid:cholesterol:DGS-NTA(Ni):MPB lipids in a 61.5:28.5:5:5 mole ratio were synthesized by lipid film rehydration and membrane extrusion using a 100 nm membrane at T > Tm(phospholipid) (DMPC = 37 °C, DPPC = 50 °C, DSPC = 60 °C), followed by post-synthesis binding of 6xHis-Cys C-terminal-modified trimer (MD39-HHHHHHC) for 1 hour at 37 °C in PBS (final concentrations 2.1 µM MD39, 3.53 mM liposomes) followed by 16–18 hr incubation at 4 °C with rotation. Non-covalent liposomes were prepared similarly without MPB lipid (phospholipid:cholesterol:DGS-NTA(Ni) lipids in a 66.5:28.5:5 mole ratio). Increasingly stabilized liposomes were prepared with 15 mole% MPB lipid and with sphingomyelin in place of cholesterol (phospholipid:sphingomyelin:DGS-NTA(Ni):MPB lipids in a 51.5:28.5:5:15 mole ratio) (In particular, page 9, whole document).
Female balb/c mice (6–10 weeks old, Jackson Laboratories) were immunized with 1 µg MD39 trimer conjugated to liposomes mixed with 0.2 U ISCOMATRIX adjuvant (CSL Ltd.) or 5 µg in-house saponin adjuvant.
Claim 2 is included in this rejection because absent evidence to the contrary the claimed MD39 liposome formulation is not incompatible with intranasal administration.
The claimed invention differs from the prior art in the recitation of wherein the albumin binding lipid is DSPE of claim 9 and wherein the linker is PEG of claim 12.
Wang et al. teaches Poly(ethylene glycol)–distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers are biocompatible and amphiphilic polymers that can be widely utilized in the preparation of liposomes, polymeric nanoparticles, polymer hybrid nanoparticles, solid lipid nanoparticles, lipid–polymer hybrid nanoparticles, and microemulsions. Particularly, the terminal groups of PEG can be activated and linked to various targeting ligands, which can prolong the circulation time, improve the drug bioavailability, reduce undesirable side effects, and especially target specific cells, tissues, and even the intracellular localization in organelles. (In particular, abstract, whole document).
Wang teaches that conventional liposomes have low bioavailability and short blood-circulation time, and are easily absorbed by the RES.77,78 Strategies have been developed to overcome these difficulties by coating the surface of the liposomes with hydrophilic polymers or a glycolipid, such as PEG or monosialoganglioside (GMI).79,80 PEG possesses high flexibility, favorable hydrophilicity, antiphagocytosis against macrophages, resistance to immunological recognition, non combination with proteins, and biocompatibility,81–84 which enable the extensive application in developing the PEGylated liposomes for delivering various drugs PEGylated liposomes have attracted considerable attention as the passive targeting administration carriers for the therapy of cancer and infectious diseases. They outweigh other carriers in increasing the systemic circulation time of drugs, delivering active molecules to the site of action and preventing damage of healthy tissue from toxic effects. During the preparation, the key step of developing long circulating liposomes was accompanied by the inclusion of the synthetic polymer PEG in the liposome composition, such as PEG-DSPE. The incorporation of PEG-DSPE in the lipid-based carriers substantially prolongs the circulation lifetime of the liposomes. Dos Santos et al2 demonstrated that merely 0.5 mol% of PEG2000-DSPE would significantly increase the plasma circulation longevity of the liposomes from 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC). The aggregation of DSPC-based liposomes was completely precluded with 2 mol% PEG2000-DSPE, suggesting that PEG2000-DSPE reduced the in vivo clearance of cholesterol free liposomal formulations and the adsorption of plasma proteins primarily by inhibiting surface interactions and particularly by liposome-liposome aggregation. The pharmacokinetics, biodistribution, and therapeutic efficacy of the PEGylated liposomes containing cisplatin and nonliposomal cisplatin were compared by Newman et al.87 They found that PEGylated liposomes had superior antitumor activity, lower kidney toxicity, and a prolonged circulation time, and also showed a 55-fold higher distribution volume, threefold higher peak plasma levels, and 60-fold larger plasma under the plasma concentration time curve (AUC) compared to those of cisplatin. Moreover, PEGylated liposome–treated animals displayed a 28-fold higher tumor AUC than for cisplatin. (In particular pages 4189-4190, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have modified the MD39-conjugated liposomes of Tokatilian et al. to use DSPE and PEG or PEG-2000 (PEG2k) because Wang et al. teaches that the key step of developing long circulating liposomes was accompanied by the inclusion of the synthetic polymer PEG in the liposome composition, such as PEG-DSPE and PEG2000-DSPE. Furthermore, it would have been obvious to have used PEG2000-DSPE because the aggregation of DSPC-based liposomes was completely precluded with 2 mol% PEG2000-DSPE. Wang et al. also teaches that PEGylated liposomes had superior antitumor activity, lower kidney toxicity, and a prolonged circulation time, and also showed a 55-fold higher distribution volume, threefold higher peak plasma levels, and 60-fold larger plasma under the plasma concentration time curve (AUC).
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the 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.
Applicant’s arguments filed on 07/08/2026 have been fully considered, but are not found persuasive.
Applicant argues:
Claims 1-7, 9-12, 24, and 26 are rejected under 35 U.S.C. § 103 as allegedly being obvious over Tokatlian in view of Wang et al. (Wang et al. 'Application of poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers and their derivatives as nanomaterials in drug delivery.' International Journal of Nanomedicine 2012:7 4185-4198, "Wang"). Applicant respectfully traverses this rejection.
As an initial matter, Applicant submits that the arguments presented above with respect to the 35 U.S.C. § 102(a)(1) rejection over Tokatlian apply equally here. As argued above, Tokatlian does not teach or suggest an amphiphilic conjugate comprising an immunogen operably linked to an albumin-binding lipid as required by claim 1. Rather, Tokatlian teaches an immunogen (MD39) displayed on the exterior surface of a liposome nanoparticle through surface attachment chemistry.
Wang does not cure the deficiencies of Tokatlian. Wang is a review article that discloses poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers as biocompatible and amphiphilic polymers that can be utilized in the preparation of liposomes,
nanoparticles, and microemulsions for prolonged circulation time (Wang, Abstract). Thus, the use of PEG-DSPE in Wang is as a structural component of the liposome bilayer membrane to confer stealth properties-not as a lipid that is conjugated to an immunogen to form an amphiphilic conjugate as required by claim 1.
Applicant submits that the Examiner's proposed combination would, at most, yield a PEGylated liposome with MD39 displayed on the surface-that is, Tokatlian's liposome architecture with PEG-DSPE incorporated into the liposome membrane from Wang. This is not an amphiphilic conjugate where the immunogen is operably linked to an albumin-binding lipid as recited in claim 1.
Neither Tokatlian nor Wang, separately or in combination teach or suggest an
amphiphilic conjugate comprising an immunogen operably linked to an albumin-binding lipid that uses albumin as a chaperone to traverse mucosal surfaces via FcRn interactions. This albumin- mediated transmucosal delivery mechanism is a fundamentally different structural and mechanistic concept from incorporating PEG-DSPE into liposome membranes for stealth properties as taught by Wang.
For at least these reasons, Applicant respectfully requests that the obviousness rejection under 35 U.S.C. § 103 be withdrawn.
It is the Examiner’s position that the term “operably linked” encompasses the covalent linkage of Tokatlian et al.
[0083] As used herein, the terms "linked", "operably linked," "fused", or "fusion", are used interchangeably. These terms refer to the joining together of two more elements or components or domains, by an appropriate means including chemical conjugation or recombinant DNA technology.
[00105] A diversity of amphiphilic conjugate structures are provided, wherein a lipophilic albumin-binding moiety, or "lipid tail" (e.g. DSPE), is linked (e.g., covalently linked) via a linker (e.g., PEG linker) to an immunogen, such as a peptide or protein antigen.
Applicant’s argument that “the liposomes of Tokatlian are multicomponent lipid vesicles comprising phospholipids (e.g., DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine)) and cholesterol or sphingomyelin (Tokatlian, pp. 8-9)” These are structural lipids that form the liposome membrane, not albumin-binding lipids operably linked to the immunogen.” is unpersuasive. Claim 7 actually recites cholesterol as an albumin binding lipid.
The specification discloses:
[0084] The term "lipid" refers to a biomolecule that is soluble in nonpolar solvents and insoluble in water. Lipids are often described as hydrophobic or amphiphilic molecules which allows them to form structures such as vesicles or membranes in aqueous environments. Lipids include fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids (including cholesterol), prenol lipids, saccharolipids, and polyketides. In some embodiments, the lipid suitable for the amphiphilic conjugates of the disclosure binds to human serum albumin under physiological conditions. In some embodiments, the lipid suitable for the amphiphilic conjugates of the disclosure inserts into a cell membrane under physiological conditions. In some embodiments, the lipid binds albumin and inserts into a cell membrane under physiological conditions. In some embodiments, the lipid is a diacyl lipid. In some embodiments, the diacyl lipid comprises more than 12 carbons. In some embodiments, the diacyl lipid comprises at least 13, at least 14, at least 15, at least 16, at least 17 or at least 18 carbons.
It is the Examiner’s position that DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), cholesterol and sphingomyelin are encompassed by the term albumin binding lipid. Applicant’s arguments about the functioning of their amphiphilic conjugate being different from the prior art are unpersuasive. The claims do not recite “the claimed amphiphilic conjugates use albumin as a chaperone to traverse mucosal surfaces via FcRn interactions. See Specification, [0106]-[0108]. This albumin-mediated transmucosal delivery mechanism requires the immunogen to be conjugated to an albumin-binding lipid, which binds to endogenous albumin and enables uptake across mucosal epithelium via the neonatal Fc receptor (FcRn).” The arguments of counsel cannot take the place of evidence in the record. In re Schulze , 145 USPQ 716, 718 (CCPA 1965). See MPEP 716.01(C). The Examiner has met the claim limitations and that is all that is required.
The rejection stands for reasons of record.
16. No claim is allowed.
17. THIS ACTION IS MADE FINAL. 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.
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (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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September 19, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
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