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 08/27/2025 is acknowledged.
3. Claims 21-22, 25-27, 29-32, 34-37 and 39 are pending.
4. Applicant’s election without traverse of Group I and the species of administering the single specific EphA2 and toll-like receptor ligand microneedle array to the single specific patient population of a patient with a solid tumor with EphA overexpression in the reply filed on 08/27/2025 is acknowledged.
5. Claims 26-27, 31-32, 34-37 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 08/27/2025. It is noted that Applicant did not elect a microneedle array with more than one adjuvant, so claims directed to microneedle arrays with more than one adjuvant have been withdrawn.
6. Claims 21-22, 25 and 29-30 are under consideration as they read on administering a EphA2 and toll receptor ligand microneedle array to a patient with a solid tumor with EphA overexpression.
7. Applicant’s IDS documents filed on 08/21/2023, 01/05/2024, 02/15/2024, 03/28/2024, 04/12/2024, 09/13/2024, 01/17/2025 and 08/27/2025 have been considered.
8. The amendment filed on 08/27/2025 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows:
“A method for promoting a pro-inflammatory and an adaptive immune response to provide a positive immunization against a solid tumor with EphA2 overexpression to a subject in need thereof, the method comprising: administering an antigen and at least one adjuvant in a cutaneous microenvironment of the subject, thereby promoting the pro-inflammatory and adaptive immune response in the subject,wherein administering the antigen and the at least one adjuvant comprises the use of one or more microneedle arrays containing the antigen and the at least one adjuvant therein.” of claim 21;
“The method of claim 21, wherein the antigen comprises EphA2.” of claim 22;
“The method of claim 21, wherein the one or more adjuvants comprise toll-like receptor-ligands (TLRs).” of claim 25;
“A method for promoting an immune response to a solid tumor with EphA2 overexpression in to a subject in need thereof, the method comprising: administering an antigen and at least one adjuvant in a cutaneous microenvironment of the subject, thereby promoting the immune response in the subject, wherein administering the antigen and the at least one adjuvant comprises the use of one or more microneedle arrays containing the antigen and the at least one adjuvant therein, wherein the antigen comprises EphA2.” of claim 29; and
“The method of claim 29, wherein the at least one adjuvant comprises toll-like receptor-ligands (TLR-s).” of claim 30.
Applicant is required to cancel the new matter in the reply to this Office Action.
9. 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.
10. Claims 21-22, 25 and 29-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a New Matter rejection for the following reasons:
Applicant' s amendment asserts that no New Matter has been added, but does not points to the specification or original claims for support for the newly added limitations:
“A method for promoting a pro-inflammatory and an adaptive immune response to provide a positive immunization against a solid tumor with EphA2 overexpression to a subject in need thereof, the method comprising: administering an antigen and at least one adjuvant in a cutaneous microenvironment of the subject, thereby promoting the pro-inflammatory and adaptive immune response in the subject,wherein administering the antigen and the at least one adjuvant comprises the use of one or more microneedle arrays containing the antigen and the at least one adjuvant therein.” of claim 21;
“The method of claim 21, wherein the antigen comprises EphA2.” of claim 22;
“The method of claim 21, wherein the one or more adjuvants comprise toll-like receptor-ligands (TLRs).” of claim 25;
“A method for promoting an immune response to a solid tumor with EphA2 overexpression in to a subject in need thereof, the method comprising: administering an antigen and at least one adjuvant in a cutaneous microenvironment of the subject, thereby promoting the immune response in the subject, wherein administering the antigen and the at least one adjuvant comprises the use of one or more microneedle arrays containing the antigen and the at least one adjuvant therein, wherein the antigen comprises EphA2.” of claim 29; and
“The method of claim 29, wherein the at least one adjuvant comprises toll-like receptor-ligands (TLR-s).” of claim 30.
The specification does not provide an adequate written description of the subject matter of any of claims 21-22, 25 and 29-30. The term “EphA2” is mentioned one time in paragraph [0269] in the specification in a list and “EphA2 (a)” and “EphA2 (b) ” are disclosed on pages 24-25 as being “epitope peptides”. This does not provide support for the claimed invention. The instant claims now recite limitations which were not clearly disclosed in the specification and claims as filed, and now change the scope of the instant disclosure as filed. Such limitations recited in the present claims, which did not appear in the specification or original claims, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. 112.
Obviousness is not the standard for the addition of new limitations to the disclosure as filed. It is noted that entitlement to a filing date does not extend to subject matter which is not disclosed, but would be obvious over what is expressly disclosed. Lockwood v. American Airlines Inc., 41 USPQ2d 1961 (Fed. Cir. 1977). New Matter is a written description issue.
The concept of the invention has changed. When an explicit limitation in a claim in not present in the written description whose benefit is sought it must be shown that a person of ordinary skill would have understood at the time the patent application was filed that the description required that limitation. The description must convey with reasonable clarity to those skilled in the art that as of the filing date sought applicant was in possession of the invention. Purdue Pharma L.P.v. Faulding Inc., 230 F.3d 1320, 1326, 56 USPQ2d 1481,1486 (Fed. Cir. 2000). The court noted that with respect to In re Ruschig 379 F.2d 990, 154 USPQ 118 (CCPA 1967) that "Ruschig makes clear that one cannot disclose a forest in the original application, and then later pick a tree out of the forest and say "here is my invention". In order to satisfy the written description requirement, the blaze marks directing the skilled artisan to that tree must be in the originally filed disclosure.
Applicant is required to cancel the New Matter in the response to this Office Action.
Alternatively, Applicant is invited to clearly point out the written support for the instant limitations.
11. Claims 21-22 and 25 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 enablement requirement. The claim(s) contains 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.
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.
The specification is not enabled for “promoting a pro-inflammatory and an adaptive immune response to provide a positive immunization against a solid tumor with EphA2 overexpression” comprising: administering “an antigen” and “at least one adjuvant” to a patient, including the administration of an adjuvant which is a toll-like receptor-ligand.
The terms “an antigen”, “at least one adjuvant” and “toll-like receptor ligand” read on a limitless number of molecules.
The specification in paragraph [0077] discloses that “As used herein, the term "antigen" means any immunogenic moiety or agent, generally a macromolecule, that elicits an immunological response in an individual.”
Although the specification does not give a formal definition for the term adjuvant, in paragraphs [0177] and [0215] the specification discloses “immune stimulant (adjuvants)”.
The specification does not define “toll-like receptor ligands” nor does it give any examples of toll-like receptor ligands. The specification discloses “R848 (TLR 7/8 ligand)” on page 25.
The specification discloses “epitope peptides” on pages 24-25 and lists “EphA2 (a)” and “EphAs (b)”. There is no indication of the structure of these two epitope peptides. Furthermore, an epitope peptide of EphA2 is not equivalent to administering EphA2 itself.
The specification is not enabled for inducing a promoting a pro-inflammatory and an adaptive immune response to provide a positive immunization against a solid tumor with EphA2 overexpression by administering any antigen any adjuvant, including the administration of any toll-like receptor-ligand adjuvant.
Since no in vivo studies were used as model system to provide positive immunization against a solid tumor with EphA2 overexpression 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 reach any therapeutic endpoint in animals by administering any antigen and any adjuvant to a patient with a solid tumor overexpressing EphA2. The specification does not teach how to develop of effective in vivo animal therapeutic treatment, commensurate in scope with the claimed invention.
In view of the absence of a specific and detailed description in Applicant's specification of how to effectively use the genus of antigens and adjuvants claimed, absence of working examples providing evidence which is reasonably predictive that the genus of antigens and adjuvants are effective for in vivo use for providing positive immunization against a solid tumor with EphA2 overexpression, 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 methods with a reasonable expectation of success.
Substantiating evidence may be in the form of animal tests, which constitute recognized screening 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 parte Maas, 9 USPQ2d 1746.
Therefore, based upon the breath of applicant's claimed invention, a skilled artisan would be unable to make and use the full breadth of applicant's claimed invention without conducting undue research.
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.
12. Claims 21-22 and 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is not in possession of: “promoting a pro-inflammatory and an adaptive immune response to provide a positive immunization against a solid tumor with EphA2 overexpression” comprising: administering “an antigen” and “at least one adjuvant” to a patient, including the administration of an adjuvant which is a toll-like receptor-ligand.
The terms “an antigen”, “at least one adjuvant” and “toll-like receptor ligand” read on a limitless number of molecules.
The specification in paragraph [0077] discloses that “As used herein, the term "antigen" means any immunogenic moiety or agent, generally a macromolecule, that elicits an immunological response in an individual.”
Although the specification does not give a formal definition for the term adjuvant, in paragraphs [0177] and [0215] the specification discloses “immune stimulant (adjuvants)”.
The specification does not define “toll-like receptor ligands” nor does it give any examples of toll-like receptor ligands. The specification discloses “R848 (TLR 7/8 ligand)” on page 25.
The specification describes “epitope peptides” on pages 24-25 and lists “EphA2 (a)” and “EphAs (b)”. There is no indication of the structure of these two epitope peptides. Furthermore, an epitope peptide of EphA2 is not equivalent to administering EphA2 itself.
The specification has not adequately described inducing a promoting a pro-inflammatory and an adaptive immune response to provide a positive immunization against a solid tumor with EphA2 overexpression by administering any antigen and any adjuvant, including the administration of any toll-like receptor-ligand adjuvant.
The skilled artisan cannot envision all the antibody and method possibilities recited in the instant claims.
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 antigens and adjuvants with the recited ability to be used to provide positive immunization against a solid tumor with EphA overexpression.
The specification must set forth the structural features that allow one of ordinary skill in the art to identify and produce the recited antigens and adjuvants to be used in the claimed method. In the instant case, definition by function does not suffice to define the genus because it is only an indication of what the antigens and adjuvants do, rather than what they are.
Thus, the skilled artisan cannot envision the detailed structure of the encompassed invention and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation.
The specification does not disclose a correlation between the antigen and adjuvant structure and the function provide positive immunization against a solid tumor with EphA overexpression such that a skilled artisan would have known what antigens and adjuvants possess the claimed function. "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 antigens and adjuvants 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 antigen and adjuvant structures are 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 antigens and adjuvants to demonstrate possession.
13. 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.
14. Claims 21-22, 25 and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Hatano et al. (PTO-892; Reference U) in view of U.S. Patent Application Publication 2015/0126923 (IDS filed on 08/21/2023) .
Hatano et al. teaches mice with EphA expressing tumors were subcutaneously vaccinated with EphA2 derived T cell epitope pulsed dendritic cells (In particular, abstract, whole document). The EphA2 peptide pulsed DC based vaccines effectively protected and treated sarcoma and melanoma (In particular, pages 4-5, whole document).
The claimed invention differs from the prior art in the recitation of administering at least one adjuvant in claims 21 and 29; administering using a microneedle array in claims 21 and 29; and administering toll-like receptor ligands as the adjuvant in claim 25 and 30.
U.S. Patent Application Publication 2015/0126923 teaches microneedle arrays for transdermal insertion which can be used to treat patients with cancer. (In particular, [0167], whole document) and for cutaneous immunization for effective delivery of antigens and adjuvants targeting cutaneous dendritic cells (In particular, paragraph [0166]). The reference teaches that the microarrays can comprise “EphA2 (a)” and “EphA2 (b)” and R848 (LRR7/8 ligand) (In particular, Table 2, paragraph [0136])
U.S. Patent Application Publication 2015/0126923 teaches “cutaneous immunization by microneedle array has important advantages in immunogenicity. The skin is rich in readily accessible dendritic cells (DCs), and has long been regarded as a highly immunogenic target for vaccine delivery. These dendritic cell populations constitute the most powerful antigen presenting cells (APCs) identified thus far. For example, genetic immunization of skin results in transfection and activation of dendritic cells in murine and human skin, and these transfected dendritic cells synthesize transgenic antigens, migrate to skin draining lymph nodes, and efficiently present them through the MHC class I restricted pathway to stimulate CD8+ T-cells. The immune responses induced by skin derived DCs are remarkably potent and long-lasting compared to those induced by other immunization approaches. Recent clinical studies demonstrate that even conventional vaccines are significantly more potent when delivered intradermally, rather than by standard intramuscular needle injection. Thus, microneedle arrays can efficiently and simultaneously deliver both antigens and adjuvants, enabling both the targeting of DCs and adjuvant engineering of the immune response using the same delivery platform. (In particular, paragraph [0228], whole document).
It would have been obvious to one of ordinary skill in the art to have applied the teachings of U.S. Patent Application Publication 2015/0126923 to Hatano et al. because both references are directed to immunization using EphA2 using dendritic cells. It would have been obvious to have applied the teachings of using a microneedle array and an adjuvant, including the particularly used toll-like receptor ligand adjuvant of R848 to treat cancer because U.S. Patent Application Publication 2015/0126923 teaches that microneedle arrays can efficiently and simultaneously deliver both antigens and adjuvants, enabling both the targeting of DCs and adjuvant engineering of the immune response using the same delivery platform.
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.
15. No claim is allowed.
16. 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 28, 2025
/Nora M Rooney/
Primary Examiner, Art Unit 1641