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 information disclosure statement (IDS) filed 05/29/2026 has been considered and the references therein are of record.
Election/Restrictions
Applicant’s election without traverse in the reply filed on 05/29/2026 is acknowledged. Applicant elects the following species:
(A) As the Type I cytokine, IL-2 (SEQ ID NO: 14);
(B) As the Type II cytokine, interleukin-33 (IL-33) (sequence, from FIG. 13A: AASVDTLSIQGTSLLTQSPASLSTYNDQSVSFVLENGCYVINVDDSGKDQEQDQ VLLRYYESPCPASQSGDGVDGKKLMVNMSPIKDTDIWLHANDKDYSVELQRGD VSPPEQAFFVLHKKSSDFVSFECKNLPGTYIGVKDNQLALVEEKDESCNNIMFKLSKI);
(C) As the type of cancer or infection, a solid tumor melanoma;
(D) As the cytokine modification to enhance in vivo half-life, conjugate to one or more albumins;
(E) As the type of cell, a CAR T- cell;
(F) As the CAR, a CAR comprising an antigen-binding domain that binds Tyrosinase- related protein 1 (TYRP1); a CD28 transmembrane domain; an CD3ζ intracellular signaling domain; a hinge derived from CD28; and a costimulatory domain derived from a cytoplasmic signaling sequence of CD28;
(G) As the form of administration, both Type I and Type II cytokines are expressed by the elected cell;
(H) As the vector, a retroviral vector;
Claim Rejections - 35 USC § 112 (b)
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 1-2, 30, 34, 45, 52, 54, and 67-68 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second I 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 1-2, 30, 34, 45, 52, 54, and 67-68 are indefinite in the recitation of the phrases “preferably,” “e.g.,” and “optionally” because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP §2173.05(d). Claim 1 is indefinite for reciting “preferably at dosages wherein said at least one cytokine (a) and (b) in combination elicit a synergistic or additive effect on immunity” and “e.g., antitumor or anti-infective immunity” because it is unclear whether the limitation of eliciting a synergistic or additive effect on immunity and the limitation of antitumor or anti-infective immunity are part of the claimed invention. Similarly, claims 2, 30, 34, 45, 52, 54, and 67-68 are likewise indefinite for reciting “preferably,” “e.g.,” and “optionally.”
Claims 2, 30, 45, 52, 54, and 67 are indefinite in the recitation of the phrases “comprising or consisting of” because it is unclear whether the claim limitations following this phrase are open-ended or not. The claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant (see MPEP 2171). Claims 52, 54, and 67 are dependent on claim 45 and are therefore included in this rejection.
Claims 2, 34, 45, 52, 54, and 67 are rejected for recitation of intended result/effect without conferring some structural or material difference on the scope of the claim. The claims recite, or are dependent upon, the functional language of binding domains that bind to a target molecule without specifying any specific structures required to perform the functions. The claims recite unspecified binding domains that can bind unspecified ligands, unspecified receptors expressed on cells, and unspecified antigens without specifying the specific structures required to perform the binding functions. It is unclear as to what agents possess the required structure to perform the functions. 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).
Claim Rejections - 35 USC § 112(a) – Written Description
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 1-2, 30, 34, 45, 52, 54, and 67-68 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.
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, or are dependent upon, a method of treating all cancers and infections (claim 1), a prophylactically effective amount of the cytokine combination (claim 1), binding domains that bind to target molecules (claims 2, 34, 45, & 54), and amino acid sequences with at least 80% identity to IL-2 (SEQ ID NO: 11) and IL-33 (subsection of SEQ ID NO: 5 spanning from position 199 to 363) that are capable of immunostimulation (claim 30), each of which encompasses a genus of agents. Claims 2 and 68 are dependent on claim 1, do not materially limit the genus of agents, and are therefore included in the rejection. Claims 52 and 67 are dependent on claim 45, do not materially limit the genus of agents, and are therefore included in the rejection. In regards to claim 1, the phrase “prophylactically effective amount” is interpreted as a method of preventing cancer or infection by administering an effective amount of the composition. 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).
From the specification, it is clear that Applicant is in possession of species of a method of treating melanoma (Fig 14; Examples) and is in possession of sequences with 100% identity to those in the Sequence Listing and the specific mutated variations recited in the specification and claims. The claims, however are not limited to those species but also includes every type of cancer, a method of preventing cancer, binding domains that bind to target molecules, and all sequences with at least 80% identity to IL-2 (SEQ ID NO: 11) and IL-33 (subsection of SEQ ID NO: 5 spanning from position 199 to 363) that are capable of immunostimulation. The specification fails to provide a representative number of species within each of the recited genera. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of the genus as a whole, or representative number of species within each genus, the specification does not provide adequate written description of the claimed genera.
Claim Rejections - 35 USC § 112(a) – Enablement
Claims 1-2, 30, 34, 45, 52, 54, and 67-68 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 the elected species, does not reasonably provide enablement for the genera of a method of treating all cancers and infections (claim 1), a prophylactically effective amount of the cytokine combination (claim 1), binding domains that bind to target molecules (claims 2, 34, 45, & 54), and amino acid sequences with at least 80% identity to IL-2 (SEQ ID NO: 11) and IL-33 (subsection of SEQ ID NO: 5 spanning from position 199 to 363) that are capable of immunostimulation (claim 30). 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 functional peptides, yet the inventors have disclosed no amino acid sequences capable of performing the functions encompassed by the genera.
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 functional peptides, a person having ordinary skill in the art would have to perform further experimentation in order to make the genera of a method of treating all cancers and infections (claim 1), a method of treating all cancer and infection by administering a prophylactically effective amount (claim 1), binding domains that bind to target molecules (claims 2, 34, 45, & 54), and amino acid sequences with at least 80% identity to IL-2 (SEQ ID NO: 11) and IL-33 (subsection of SEQ ID NO: 5 spanning from position 199 to 363) that are capable of immunostimulation (claim 30) 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 functional peptides, then use those in the method claimed 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 1-2, 30, 34, 45, 52, 54, and 67-68 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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Wang et al., 2019 (US20190216898A1) (see IDS Document).
Claim 1 is drawn to a method of treating cancer or infection, the method comprising administering to a subject in need thereof an immunostimulatory cytokine combination comprising a prophylactically or therapeutically effective amount of (a) the Type I cytokine, IL-2, and (b) the Type II cytokine, IL-33, where they cytokines are administered in the same compositions and at dosages where the cytokines in combination elicit a synergistic or additive effect on immunity compared to the administration of either cytokines alone.
Wang teaches a method of treating melanoma by administering to a subject a composition comprising T-cells capable of producing the recombinant protein or comprise the recombinant nucleic acid molecule or vector, where the recombinant protein comprises IL-2 and IL33, which in combination synergistically activates an anti-tumor immune response (claims; examples; & para[0002-0007, 0053, 0083, 0110, & 00114]).
Therefore, Wang anticipates instant claim 1.
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 1-2, 30, 34, 45, 52, 54, and 67-68 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., 2019 (US20190216898A1) in view of MacKall et al., 2019 (US20190183932A1), Austin et al., 2002 (US20020041865A1), and Schmitz et al., 2005 (US20050203046A1) (see IDS Document).
The elected instant claims are drawn to a method of treating melanoma by administering to a subject a CAR T-cell that binds a melanoma cell triggering co-release by the CAR T-cell of IL-2 (with sequence identity as set forth in SEQ ID NO:14) and IL-33 (with sequence identity as set forth in subsection of SEQ ID NO: 5 spanning from position 199 to 363) which in combination additively or synergistically activates the endogenous immune response providing for enhanced inhibition of tumor growth and/or metastasis compared to administration of either cytokine alone. The elected instant claims are drawn to the cytokines being modified with one or more albumins to enhance in vivo half-life. The elected instant claims are drawn to the CAR comprising an antigen-binding domain that binds Tyrosinase- related protein 1 (TYRP1), a CD28 transmembrane domain, an CD3ζ intracellular signaling domain, a hinge derived from CD28, and a costimulatory domain derived from a cytoplasmic signaling sequence of CD28. The elected instant claims are drawn to a nucleic acid and viral vector encoding the cytokines and CAR. The elected instant claims are drawn to a composition comprising the CAR T-cell that expresses the cytokines along with a pharmaceutically acceptable excipient or carrier.
Wang teaches a method of treating melanoma by administering to a subject a composition comprising T-cells capable of producing the recombinant protein or comprise the recombinant nucleic acid molecule or vector, where the recombinant protein comprises IL-2 and IL33, which in combination synergistically activates an anti-tumor immune response (claims; examples; & para[0002-0007, 0053, 0083, 0110, & 00114]). Wang teaches the cytokines being modified with one or more albumins to enhance in vivo half-life (claims & para[0049 &0064-0066]). Wang teaches the composition comprises a pharmaceutically acceptable carrier (para[0093]). Wang teaches the composition further comprises the recombinant peptide fused with a tumor-targeting peptide (claims & para[0049, 0067, 0076, & 00160]). Wang teaches the vector being a retroviral vector (claims, example 1, & para[0051-0052, 0076, & 0102-0109]).
Wang does not explicitly teach the T cell being a CAR T-cell. Wang does not explicitly teach the CAR T-cell with the CAR comprising an antigen-binding domain that binds Tyrosinase-related protein 1 (TYRP1), a CD28 transmembrane domain, an CD3ζ intracellular signaling domain, a hinge derived from CD28, and a costimulatory domain derived from a cytoplasmic signaling sequence of CD28. Wang does not explicitly teach an IL-2 that has sequence identity as set forth in instant SEQ ID NO: 8. Wang does not explicitly teach an IL-33 that has sequence identity as set forth in position 199 to 363 of instant SEQ ID NO: 5.
MacKall teaches a method of treating melanoma by administration of a composition that comprises CAR T-cells, where the CAR comprises an antigen-binding domain that binds TRP1, a CD28 transmembrane domain, an CD3ζ intracellular signaling domain, a hinge derived from CD28, and a costimulatory domain derived from a cytoplasmic signaling sequence of CD28 (examples; para[0013, 0059, 00124-00128, 00136-0137, & 0204]; & Fig. 14A & 15B).
Austin teaches an IL-2 fusion peptide, where the IL-2 has the sequence set forth in SEQ ID NO: 8 (Db) that has 100% sequence identity to instant SEQ ID NO: 14 (Qy), as shown below.
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320
644
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Schmitz teaches an IL-33 having the sequence set forth in SEQ ID NO: 4 (Db) that has 100% sequence identity to position 199 to 363 of instant SEQ ID NO: 5 (Qy), as shown below.
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327
665
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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 Wang, MacKall, Austin, and Schmitz. One with ordinary skill in the art would be motivated to make and use the claimed invention because Wang teaches the composition is useful to treat melanoma and an ordinary artisan would look to the prior art to obtain the sequences in order to synthesize and use the composition taught by Wang. An ordinary artisan would be motivated to look to the prior art to obtain the sequences to know how to construct the vector/peptide that will be used in the T cell treatment for melanoma. Upon obtaining these sequences, an ordinary artisan would be motivated, and find it obvious, to combine the teachings of Wang and MacKall to make an improved T cell composition. An ordinary artisan would find it obvious that both Wang and MacKall teach compositions that are useful for the same purpose of treating melanoma, and would therefore be obvious to combine to make a better treatment. Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements/compositions each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from them having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). But nevertheless, an ordinary artisan would be motivated to use a more effective type of T cell to optimize Wang’s composition and make the most effective melanoma treatment. 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. Thus, the claims do not contribute anything non-obvious over the prior art.
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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