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 .
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claim 11 is objected to because it references Table 1 in the specification. Claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). See MPEP § 2173.05.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-7, 9, 11, 22-23, 25, 27, 29, and 32 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 1-7, 9, 11, 22-23, 25, 27, 29, and 32 are rejected for recitation of intended result/effect without conferring some structural or material difference on the scope of the claim. Claims 1-4, 6-7, 9, 11, 22-23, 25, and 27 recite the functional language of a first responder (FR)-targeting agent, TLR agonist, TLR9 agonist, TLR7 agonist, agent capable of binding to a protein of Table 1, PRG2-binding agent, DAP12-binding agent, CD206-targeting agent, C9orfl35- targeting agent, TMEM176A-binding agent, TREM2-binding agent, and CLC5A- binding agent without specifying any specific structures required to perform the requisite functions. The claims are indefinite because it is unclear as to what structures are necessary to provide the claimed targeting, agonist, and binding functions. Claims 5, 29, and 32 do not clarify the requisite structures and are therefore included in this rejection. The mechanism steps and requisite structure are merely implied by the functional language and thus the scope of the claim is undefined. Absent additional active method steps and structure, it is unclear how these claims further limit the scope of the parent claim. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim' and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim.” The claims are rejected since they fail to meet all (3) criteria set forth in MPEP 2173.05(g).
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 1-7, 9, 11, 22-23, 25, 27, 29, and 32 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 claims contain 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. The claims recite an antigen, a polynucleotide encoding an antigen, a first responder (FR)-targeting agent, TLR agonist, TLR9 agonist, TLR7 agonist, agent capable of binding to a protein of Table 1, PRG2-binding agent, DAP12-binding agent, CD206-targeting agent, C9orfl35- targeting agent, TMEM176A-binding agent, TREM2-binding agent, CLC5A- binding agent, and a composition comprising an antigen and FR-targeting agent capable of treating and preventing cancer, an autoimmune condition, or inflammatory condition, each of which encompasses a genus of agents. These claims do not require that the genera of the claims possess any particular structure or other distinguishing feature that is characteristic of the genera as a whole. Therefore the claims are drawn to genera for which there is inadequate written description.
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 (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 claimed genus MPEP 2163(II)(3)(a)(i)(C).
The specification provides evidence that the applicant is in possession of liposomes linked to the targeting agents heparin and peptides of SEQ ID NOs: 1-2 that are loaded with the antigen ovalbumin plus adjuvants CpG and R848 used to increase anti-ovalbumin titers and treat an artificially engineered ovalbumin-expressing tumor model in mice. The specification does not provide evidence of possession of a representative number of species for the claimed genera, such as any antigen, any FR-targeting agent, any agonist of TLR/TLR9/TLR2, and any agent capable of binding the proteins recited above. Further, the specification provides no evidence of possession of any composition that can treat and prevent any disease, cancer, autoimmune, or inflammatory condition. The specification only provides evidence of treating an artificial, non-human tumor model that is not representative of any and all cancers. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of the genus as a whole, or representative number of species within the genus, the specification does not provide adequate written description of the claimed genera.
Claims 1-7, 9, 11, 22-23, 25, 27, 29, and 32 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 liposomes linked to the targeting agents heparin and peptides of SEQ ID NOs: 1-2 that are loaded with an antigen plus adjuvants, does not reasonably provide enablement for the genera of a first responder (FR)-targeting agent, TLR agonist, TLR9 agonist, TLR7 agonist, agent capable of binding to a protein of Table 1, PRG2-binding agent, DAP12-binding agent, CD206-targeting agent, C9orfl35- targeting agent, TMEM176A-binding agent, TREM2-binding agent, CLC5A- binding agent, and a composition comprising an antigen and FR-targeting agent capable of treating and preventing cancer, an autoimmune condition, or inflammatory condition. 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 use the invention commensurate in scope with these claims.
In AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies that perform these two functions.
The case law applies to the instant claims which require multiple genera of targeting agents, agonist, binding agents, and compositions with the functional capability of treating and preventing any and all cancers, autoimmune conditions, and inflammatory conditions. Said another way, a person having ordinary skill in the art would not know how to make any and all agents that possess the claimed targeting, agonistic, and binding capabilities and then use them in the claimed composition to treat and prevent any and all cancers, autoimmune conditions, and inflammatory conditions.
In Amgen, the Supreme Court has stated:
“An antibody' s structure does much to dictate its function—its ability to bind to an antigen and, in some instances, to block other molecules in the body from doing the same. ‘For an antibody to bind to an antigen, the two surfaces have to fit together and contact each other at multiple points.' Id., at 11. But just because an antibody can bind to an antigen does not mean that it can also block. To bind and block, the antibody must establish a sufficiently broad, strong, and stable bond to the antigen. See ibid. Different antibodies have different binding and blocking capacities based on the amino acids that compose them and their three-dimensional shapes. See id., at 11–12.
Despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody' s structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody' s structure and function. Ibid.”
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentec, Inc., V. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that: "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" and that "[t]ossing out the mere germ of an idea does not constitute enabling disclosure". The court further stated that "when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all of the disclosure related to the process is within the skill of the art","[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement". The instant specification is not enabling for the full scope of the claimed invention because one cannot follow the guidance presented therein and practice the claimed method without first making a substantial inventive contribution.
Given that structure is essential to function; and given the unpredictability within the art with respect to creating antibodies, agonists, binding agents, and disease treatments, a person having ordinary skill in the art would have to perform further experimentation in order to make the vast array of species within the genera of a first responder (FR)-targeting agent, TLR agonist, TLR9 agonist, TLR7 agonist, agent capable of binding to a protein of Table 1, PRG2-binding agent, DAP12-binding agent, CD206-targeting agent, C9orfl35- targeting agent, TMEM176A-binding agent, TREM2-binding agent, CLC5A- binding agent, and a composition comprising an antigen and FR-targeting agent capable of treating and preventing cancer, an autoimmune condition, or inflammatory condition encompassed by the claims and use them in the method claimed, commensurate in scope with the breadth of the claims. Given the nature of the invention, a skilled artisan would have to make many targeting agents, agonist, and binding agents, then use those in the method claimed of treating and preventing any and all cancers, autoimmune conditions, and inflammatory conditions in order to demonstrate making and using with a reasonable expectation of success. This amount of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the method for the breadth of what is claimed.
Thus, claims 1-7, 9, 11, 22-23, 25, 27, 29, and 32 lack enablement.
Claim Rejections - 35 USC § 102
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.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-11, 22, 29, and 32 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Moniz et al., 2020 (WO2020191361A2) (see instant PTO-892).
The instant claims are drawn to a pharmaceutical composition comprising an antigen, or a polynucleotide encoding an antigen, and a first responder (FR)-targeting agent. The instant claims are drawn to the FR-targeting agent conjugated to the antigen, the FR-targeting agent conjugated to a liposome comprising the antigen, and the FR- targeting agent conjugated to a nanoparticle comprising the antigen. In some embodiments, the instant claims are drawn to the composition further comprising the adjuvants of CpG oligodeoxynucleotide TLR9 agonist and R848. The instant claims are drawn to the composition containing a second FR-targeting agent. The FR-targeting agents are drawn to agents capable of binding to a protein of Table 1, PRG2-binding agent, DAP12-binding agent, CD206-targeting agent, C9orfl35- targeting agent, TMEM176A-binding agent, TREM2-binding agent, or CLC5A- binding agent. The instant claims are drawn to the antigen being a tumor, viral, or bacterial antigen. The claims are further drawn to a method of administering the pharmaceutical composition to stimulate an immune response to an antigen, treat or prevent cancer, or treat or prevent an autoimmune or inflammatory condition in a subject.
Moniz teaches that nanoparticles and liposomes can be conjugated via linkers and scaffolding to tumor antigens, viral antigens, bacterial antigens, targeting agents, binding peptides, and therapeutic drugs, such as a targeting moiety that binds CD206, and further comprise adjuvants, such as a TLR7/8 agonist, Resiquimod, and a TLR9 agonist, unmethylated CpG DNA (abstract, claims, examples, & para[0034, 0039, 0141, 0147, 0170-0178, 0180, 0220, & 0239]). Moniz teaches the composition can stimulate an immune response to an antigen (abstract, claims, para[0091]). Moniz teaches “EVs (e.g. , exosomes) of the present disclosure differ from traditional vaccines in that the EVs can be rapidly engineered to express a moiety of interest (e.g, antigen, adjuvant, immune modulator, and/or targeting moiety). As described herein, the moieties of interest (i) can be directly linked to a surface of the EV (e.g, exterior surface and/or luminal surface), (ii) can be linked to a scaffold moiety (e.g, Scaffold X and/or Scaffold Y) and then expressed on a surface of the EV (e.g, exterior surface and/or luminal surface), (iii) can be expressed in the lumen of the EV, or (iv) combinations thereof. Such ability to rapidly engineer EVs (e.g, exosomes) is particularly useful in developing EV (e.g, exosome)-based vaccines. For instance, a single EV (e.g, exosome) engineered to express certain payloads and/or targeting moieties can be used in treating a wide range of diseases or disorders by simply ‘plugging’ an antigen of interest into the EVs. Accordingly, in some aspects, the present disclosure is directed to methods of producing such modular or ‘plug and play’ EV ( e.g ., exosome) vaccines.” (para[0495-0496])
Therefore, Moniz anticipates instant claims 1-11, 22, 29, and 32.
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 12 and 23-28 are rejected under 35 U.S.C. 103 as being unpatentable over Moniz et al., 2020 (WO2020191361A2), as applied to claims 1-11, 22, 29, and 32 above, in view of Sigalov et al., 2019 (US20190117725A1), Jaynes et al., 2020 (US20200069765A1), and Duehrkop et al., 2016 (see instant PTO-892).
The instant claims are drawn to FR-targeting agents being heparin and a DAP 12-binding agent comprising SEQ ID NO: 1. The instant claims are drawn to FR-targeting agents being heparin and a CD206-binding agent comprising SEQ ID NO: 2. The instant claims are drawn to FR-targeting agents being a DAP 12-binding agent comprising SEQ ID NO: 1 and a CD206-binding agent comprising SEQ ID NO: 2.
The teachings of Moniz are recited above.
Moniz does not explicitly teach the DAP12 binding agent as set forth in instant SEQ ID NO: 1, CD206-binding agent as set forth in instant SEQ ID NO: 2, or heparin. Sigalov, Jaynes, and Duehrkop remedy these deficiencies.
Sigalov teaches a DAP12 binding agent peptide as set forth in SEQ ID NO: 52 (Db) that has 100% sequence identity to instant SEQ ID NO: 1 (Qy), as shown below, that can be conjugated to a therapeutic drug, can be loaded into a lipid nanoparticle vesicle, can modulate immune cell activity, and can be used as a drug delivery system for treatment of cancer, inflammatory conditions, and autoimmune diseases (abstract & para[0002, 0030, 0049, 0114-0115, & 0194-0196]).
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Jaynes teaches a CD206-binding agent peptide as set forth in SEQ ID NO: 1 (Db) that has 100% sequence identity to instant SEQ ID NO: 2 (Qy), as shown below, that can be conjugated/linked to an targeting therapeutic antigen, can be conjugated to a lipid, can be loaded into a nanocarrier and liposome, can be used in a vaccine, can stimulate an immune response, and can be used to treat cancer, inflammatory conditions, and autoimmune diseases (examples 1-2, claims, & para[0167-0168, 0170-0176, 0184-0185, 0188-0191, 0204-0207, & 0211-0215]).
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Duehrkop teaches that liposomes containing heparin improves drug delivery, stabilizing and protecting liposomes against adverse immune reactions (Title & Abstract).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosures of Sigalov, Jaynes, Duehrkop and Moniz. In view of Moniz’s teaching on ‘plug and play’ liposome vaccines, an ordinary artisan would be motivated to use the DAP12 binding agent taught by Sigalov to make the claimed invention because Moniz does not provide specific amino acid sequences that could be used as targeting agents which would motivate an ordinary artisan to search for specific binding agents capable of stimulating an immune response that can be plugged into the liposome vaccine. This same logic would motivate an ordinary artisan to use the CD206-binding agent peptide taught by Jaynes in the ‘plug and play’ liposome vaccine. An ordinary artisan would readily understand and find it obvious that both of the binding agents taught by Sigalov and Jaynes would be useful in the vaccine composition to target antigens loaded in liposomes to immune cells, stimulating an immune response. An ordinary artisan would find it obvious that these specific amino acid sequences could readily be ‘plugged’ into the scaffolding of the liposome to make a useful vaccine composition that could be further tested to determine its efficacy in the treatment of various cancers. Furthermore, an ordinary artisan would find it obvious to incorporate heparin into the liposome composition in view of Duehrkop that heparin improves drug delivery, as well as stabilizing and protecting liposomes against adverse immune reactions. This would be the motivation that would drive an ordinary artisan to make and use the claimed invention because an ordinary artisan would want to optimize the efficacy of the vaccine. It would be clear to an ordinary artisan that the incorporation of heparin would improve the vaccine composition that is obvious in view of Moniz, Sigalov, and Jaynes. The person of ordinary skill in the art would have had a reasonable expectation of success based on the disclosures of these prior art references. Therefore, claims 12 and 23-28 are obvious.
Conclusion
No claims are allowed.
Advisory Information
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/JOSEPH D. CESARE/ Examiner, Art Unit 1675 /JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675
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