DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
Claims 10, 11, 16, 18-21, 23-28, 32-37, 39, and 41-47 are cancelled.
Claims 1-9, 12-15, 17, 22, 29-31, 38, and 40 are pending.
Election/Restrictions
Applicant’s election without traverse of Group V, claims 1-3, 7-9, and 12, drawn to a method of regulating immune responses or resisting tumors comprising administering an antibody that recognizes and binds to ITPRIPL1, in the reply filed on 02 February 2026 is acknowledged.
Claims 4-6, 13-15, 17, 22, 29-31, 38, and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02 February 2026.
Claims 1-3, 7-9, and 12 are under consideration in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 28 April 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. It is noted that the Dausinas reference has been crossed out because the reference is missing text and is completely illegible.
Drawings
1. The drawings are objected to because:
(1a) Figures 53, 54, 55, and 56 contain views that have an incorrect orientation. References characters, sheet numbers, and view numbers must be oriented in the same direction as the view so as to avoid having to rotate the sheet (see 37 CFR 1.84(p)(1)).
(1b) In Figures 1A-1B, 4A-4B, 5, 6A-6E, 8, 9A-9B, 10, 11A-11B, 12, 13A-13B, 14, 18, 21A-21B, 22, 25A-25C, 27A-27B, 28, 29A-29C, 31A-31D, 33A, 34, 37, 38, 44, 54, 55, 58A-58L, 65A-65B, 66A-66M, and 67A-67N, the text and numbers are blurry and/or too small, making the information illegible and difficult for the Examiner to interpret the data presented therein (see 37 CFR 1.84(p)). Applicant is reminded that numbers, letters, and reference characters must measure at least .32 cm. (1/8 inch) in height.
(1c) In Figure 54, the text on top of shaded areas is also difficult to read. It is suggested to remove the shading.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
2. Specific deficiencies and the required response to this Office Action are as follows:
2a. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Please see page 4, [0014]; page 71, [0315]; page 72 [0317].
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
2b. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Please see Figures 1C, 4C, 54, and 65C.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
3. The disclosure is objected to because of the following informalities:
3a. The Brief Description of the Drawings does not refer to Figures 1A-1C, 2A-2D, 3A-3D, 4A-4C, 5A-5B, 6A-6E, 19A-19C, 31A-31D, and 39A-39B.
3b. The Brief Description of the Drawings at page 14, [0083] refers to 37(a) and 37(b). However, Figure 37 does not contain labeled subparts (a) and (b).
Appropriate correction is required.
Claim Objections
4. Claims 1-3, 7-9, and 12 are objected to because of the following informalities:
4a. Claims 1-3, 9, and 12 recite the acronym “ITPRIPL1” without first defining what it represents. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim.
4b. In claim 2, subparts (1)-(5) should be renumbered utilizing “(i)-(v)” or “(a)-(e)” so as to prevent confusion with claim numbering.
4c. In claim 2, line 7, after the phrase “protein;”, the word “and” or “or” should be inserted.
4d. In claim 2, line 8, the word “the” recited before “ITPRIPL1” is extraneous and should be deleted.
4e. In claim 3, line 8, after the phrase “protein;”, the word “and” or “or” should be inserted.
4f. In claim 7, line 4, after the phrase “immune responses,” the word “and” or “or” should be inserted.
4g. In claim 8, line 3, after the phrase “cytokine storm”, the word “and” or “or” should be inserted.
Appropriate correction is required.
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.
5. Claims 1-3, 7-9, and 12 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.
5a. Claims 1-3, 7-9, and 12 are rejected as being indefinite because the phrase “resisting tumors” in claims 1 and 12 is a relative phrase which renders the claims indefinite. The phrase “resisting tumors” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, according to dictionary.com, the term “resist” means to withstand, strive against, oppose, to stand firm against, not yield to, or fight against (see attached dictionary entry at pages 1 and 2; www.dictionary.com/browse/resist, dated 14 April 2026). As the specification does not provide a specific definition for “resist/resisting tumors” and in view of the common definition, it is not clear if the phrase as recited in the instant claims encompasses treating tumors, preventing tumors, or something else entirely.
5b. Claims 7 and 8 are rejected as being indefinite because in claim 7, lines 1-2 recite “regulating of immune responses comprises:”. Immediately after this phrase, lines 2-4 also recite “regulating the functions of antigen presenting cells and T lymphocytes during the processes of autoimmune responses, transplant-rejection-suppressing immune responses, allergies, anti-infection immune responses, anti-tumor immune responses”. Therefore, it is not clear if the activities recited in lines 2-4 refer back to “regulating of immune responses” or “regulating the functions of antigen presenting cells and T lymphocytes during the processes of…”. If lines 2-4 are intended to refer back to the regulated immune responses (in lines 1-2), it is suggested to separate each of the activities recited in lines 3-4 with semi-colons or labeled subparts (i.e., (i), (ii), (a), (b), etc.).
5c. Claim 12 recites the limitation "the ITPRIPL1 protein" in line 3. There is insufficient antecedent basis for this limitation in the claim. Line 2 only recites “ITPRIPL1”. There is no recitation of “an ITPRIPL1 protein”.
Claim Rejections - 35 USC § 112(a)
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.
6. Claims 1-3, 7-9, and 12 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.
Claim 1 is directed to a method of regulating immune responses or resisting tumors, comprising administrating a regulator of ITPRIPL1, wherein the regulator is used to increase or decrease the expression or function of the ITPRIPL1 gene or protein in an organism.
Instant claim 2 recites that the regulator comprises an antibody that recognizes and binds to the ITPRIPL1.
Claim 3 recites that the antibody that recognizes and binds to ITPRIPL1 is a polyclonal antibody, a monoclonal antibody, a single-stranded antibody, an antigen binding domain, a bispecific antibody, a multi-specific antibody, or an antigen binding portion in a chimeric antigen receptor.
Claim 12 recites a method of regulating immune responses or resisting tumors, comprising administrating an antibody that recognizes and binds to ITPRIPL1, wherein the antibody recognizes and binds to the extracellular domain of the ITPRIPL1 protein.
The specification of the instant application teaches the present disclosure is based on a new scientific discovery that ITPRIPL1 binds to proteins such as CD3ε, so as to regulate the functions of different immune cells, and then participate in the regulation of immune responses and the immune evasion process of tumors (page 10, [0054]; page 39, [0214]). The specification also discloses that the present disclosure develops a targeting antibody that can bind to ITPRIPL1 with high affinity and neutralize its function (page 10, [0051]). The specification teaches the generation of polyclonal and monoclonal antibodies to ITPRIPL1, with ITPRIPL1-RBD (receptor binding domain) as an immunogen (pages 50-57, Example 6; pages 90-93, Example 19). The specification teaches that the capacity of binding to ITPRIPL1 varies among antibodies (indicating heterogeneity), with antibodies “13B7” and “18B12” as the antibodies with the best binding (page 92, [0403]; Figure 57; page 93, [0406]; Example 20; page 96, [0419]).
Additionally, the specification discloses that for monoclonal antibody, “13B7A6H3”, the heavy chain amino acid sequence is set forth in SEQ ID NO: 22; the light chain amino acid sequence is set forth in SEQ ID NO: 23; the heavy chain variable region (VH) amino acid sequence is set forth in SEQ ID NO: 24; and the light chain variable region (VL) amino acid sequence is set forth in SEQ ID NO: 25 (page 100, [0436]). For monoclonal antibody, “18B12D1A6”, the heavy chain amino acid sequence is set forth in SEQ ID NO: 32; the light chain amino acid sequence is set forth in SEQ ID NO: 33; the heavy chain variable region (VH) amino acid sequence is set forth in SEQ ID NO: 34; and the light chain variable region (VL) amino acid sequence is set forth in SEQ ID NO: 35 (pages 100-101, [0436]).
However, the instant claims only recite administration of an antibody that recognizes and binds to ITPRIPL1. The teachings of the specification are not adequate written description of an entire genus of antibodies that (i) recognize and bind to ITPRIPL1, (ii) increase or decrease the expression or function of the ITPRIPL1 gene or protein, and (iii) regulate immune responses or resist tumors.
The first paragraph of 35 U.S.C. § 112 "requires a 'written description of the invention' which is separate and distinct from the enablement requirement." Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991). An adequate written description of a chemical invention "requires a precise definition, such as by structure, formula, chemical name, or physical properties." University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004); Regents of the Univ. of Cal. v. Eli Lilly & Co., Inc., 119 F.3d 1559, 1566 (Fed. Cir. 1997); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993). "A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F.3d at 923; Eli Lilly, 119 F.3d at 1568. Instead, the "disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described." Id. In addition, possession of a genus "may be achieved by means of a recitation of a representative number of [compounds]... falling within the scope of the genus." Eli Lilly, 119 F.3d at 1569. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus. See Rochester, 358 F.3d at 927.
Thus, case law dictates that to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include actual reduction to practice, disclosure of drawings or structure chemical formulas, sufficient relevant identifying characteristics (such as, complete or partial structure, physical and/or chemical properties, and functional characteristics when coupled with a known or disclosed structure/function correlation), methods of making the claimed product, level of skill and knowledge in the art, predictability in the art, or any combination thereof. In the instant case, the only factors present in the method claims are (i) a structural characteristic of an antibody and (ii) functional characteristics of recognizing/binding to ITPRIPL1, increasing/decreasing the expression or function of the ITPRIPL1 gene or protein, and regulating immune responses or resisting tumors. There is no other identification of any particular sequence or structure of the antibody in the instant claims. There is also no identification of any particular sequence or structure that must be conserved in order to provide the required functions of recognizing/binding to ITPRIPL1, increasing/decreasing the expression or function of the ITPRIPL1 gene or protein, and regulating immune responses or resisting tumors.
Thus, the claims are drawn to a genus of antibodies that (i) recognize and bind to ITPRIPL1, (ii) increase or decrease the expression or function of the ITPRIPL1 gene or protein, and (iii) regulate immune responses or resist tumors. In this case, the specification fails to disclose and there is no art-recognized correlation between the structure of the genus of antibodies and the required functions of recognizing/binding to ITPRIPL1, increasing/decreasing the expression or function of the ITPRIPL1 gene or protein, and regulating immune responses or resisting tumors. In other words, the specification does not teach the structure (i.e., heavy and light chain variable domains or CDRs) which results in an antibody with the claimed required characteristics.
The description of two monoclonal anti-ITPRIPL1 antibodies, termed “13B7A6H3” and “18B12D1A6” that neutralize ITPRIPL1 in the instant specification, is not adequate written description of an entire genus of antibodies that recognize/bind to ITPRIPL1, increase/decrease the expression or function of the ITPRIPL1 gene or protein, and regulate immune responses or resist tumors. Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one or two species within the genus (Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
The instant claims are attempting to claim administration of every antibody that would achieve a desired result, i.e., recognizing/binding to ITPRIPL1, increasing/decreasing the expression or function of the ITPRIPL1 gene or protein, and regulating immune responses or resisting tumors, whereas the specification does not describe representative examples to support the full scope of the claims. Applicant is reminded that "when a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the same result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). However, in the instant case, the specification does not disclose the generation of a genus of antibodies that (i) recognize and bind to ITPRIPL1, (ii) increase or decrease the expression or function of the ITPRIPL1 gene or protein, and (iii) regulate immune responses or resist tumors. Therefore, the specification does not provide adequate written description of an entire genus of antibodies that achieve a desired result, i.e., recognizing/binding to ITPRIPL1, increasing/decreasing the expression or function of the ITPRIPL1 gene or protein, and regulating immune responses or resisting tumors.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (See page 1117). See also, Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (See Vas-Cath at page 1116). A “mere wish or plan” to obtain the claimed invention is not sufficient (Centocor Orth Biotech, Inc. v. Abbott Labs, 636 F.3d 1341 (Fed. Cir. 2011); Regents of the Univ. of California, 119 F.3d at 1566). In the instant application, the skilled artisan cannot envision the detailed chemical structure of the antibodies of the encompassed method claims, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The specific antibody is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. It is well-known in the art that antibodies have a large repertoire of distinct structures and that a large variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. teach that over hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. Protein Engineering, Design & Selection 22:159-168, 2009; see, e.g., Discussion). Edwards et al. (J Mol Biol 334: 103-118, 2003; see abstract) also teach that over 1,000 different antibodies to a single Blys protein can be generated, all with different sequences, and representative of almost the entire extensive heavy and light chain germline repertoire, in addition to extensive diversity in the hCDR3 region sequences. Given that hundreds of unique antibody structures may bind a single antigen, one species or small group of related species cannot be representative of all the antibodies that bind to the same epitope. Given the unpredictability of the structures of the large number of antibodies that could bind to ITPRIPL1 encompassed by the claims, the instant specification does not describe representative examples to support the full scope of the claims. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant’s attention is directed to the recent decision in Amgen Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The court discussed whether an antibody is adequately described by describing a newly characterized antigen. Specifically, the court referred to the decision in Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011). In that case, the patentee claimed a genus of antibodies containing a human variable region that has particularly desirable therapeutic properties: high affinity, neutralizing activity, and A2 specificity. Despite the fact that the specification disclosed human TNF-α protein, the court ruled that that the generic antibody claims at issue were invalid for lack of written description, despite the disclosure of the structures of more than one species of antibody encompassed in the genus. The fact pattern is similar in the instant case. Specifically, in the instant case, the structure of the ITPRIPL1 protein is provided by the amino acid sequence of SEQ ID NOs: 20 and 72 (for example), while specific structures for antibodies that recognize/bind to ITPRIPL1, increase/decrease the expression or function of the ITPRIPL1 gene or protein, and regulate immune responses or resist tumors are not. As in the court case, the instant claims recite a genus of antibodies that have a desirable therapeutic property, i.e., recognizing/binding to ITPRIPL1, increasing/decreasing the expression or function of the ITPRIPL1 gene or protein, and regulating immune responses or resisting tumors. Following the finding in Centocor, the instant claims are found to lack adequate written description.
The court in Amgen v. Sanofi further compares the requirements of enablement and written description, stating that:
“We cannot say that this particular context, involving a “newly characterized antigen” and a functional genus claim to corresponding antibodies, is one in which the underlying science establishes that a finding of “make and use” (routine or conventional production) actually does equate to the required description of the claimed products. For us to draw such a conclusion, and transform a factual issue into a legally required inference, we would have to declare a contested scientific proposition to be so settled as to be entitled to judicial notice. That we cannot do.”
The court indicated that it has been hotly disputed whether or not knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. Citing Centocor again, the court provides an analogy for the antibody-antigen relationship as not quite a lock and key relationship but rather providing a lock and then searching for a key on a ring with a million keys on it. The court concludes that the “newly characterized antigen” test flouts basic legal principles of the written description requirement, reasoning that section 112 requires a written description of the invention, whereas the newly characterized antigen test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The court urges that such constricts the “quid pro quo” of the patent system where one describes an invention in order to obtain a patent.
Accordingly, since the instant fact pattern fits the “newly characterized antigen” scenario, wherein the specification describes the structure of the target/antigen but not the structure of the genus of antibodies, the claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Only administration of an isolated antibody that binds and inhibits ITPRIPL1, wherein the antibody comprises (i) the six CDR amino acid sequences of SEQ ID NOs: 26-29, KV, and 31; (ii) the heavy chain variable domain (VH) amino acid sequence of SEQ ID NO: 24 and the light chain variable domain (VL) amino acid sequence of SEQ ID NO: 25; (iii) the six CDR amino acid sequences of SEQ ID NOs: 36-39, KV, and 41; or (iv) the heavy chain variable domain (VH) amino acid sequence of SEQ ID NO: 34 and the light chain variable domain (VL) amino acid sequence of SEQ ID NO: 35, but not the full breadth of claims, meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). See also Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010).
7. Claims 1-3, 7-9, and 12 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 (A) a method of enhancing the activity and/or infiltration of T cells in a cancer or tumor that overexpresses ITPRIPL1 and (B) a method of treating a cancer or tumor that overexpresses ITPRIPL1, comprising administering to a subject in need thereof an antibody that binds and inhibits ITPRIPL1, does not reasonably provide enablement for a method of regulating immune responses in an organism or a method of resisting tumors or regulating anti-tumor responses comprising administering an antibody that recognizes and binds ITPRIPL1. 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.
Claim 1 is directed to a method of regulating immune responses or resisting tumors, comprising administrating a regulator of ITPRIPL1, wherein the regulator is used to increase or decrease the expression or function of the ITPRIPL1 gene or protein in an organism.
Instant claim 2 recites that the regulator comprises an antibody that recognizes and binds to the ITPRIPL1.
Claim 7 recites that regulating of immune responses comprises: regulating the functions of antigen presenting cells and T lymphocytes during the processes of autoimmune responses, transplant-rejection-suppressing immune responses, allergies, anti-infection immune responses, anti-tumor responses.
Instant claim 8 recites that the immune responses comprise: type I diabetes, immunologic fertility, rejection after organ transplantation, allergies, systemic inflammation or cytokine storm, infection.
Claim 12 recites a method of regulating immune responses or resisting tumors, comprising administrating an antibody that recognizes and binds to ITPRIPL1, wherein the antibody recognizes and binds to the extracellular domain of the ITPRIPL1 protein.
The specification of the instant application teaches the present disclosure is based on a new scientific discovery that ITPRIPL1 binds to proteins such as CD3ε, so as to regulate the functions of different immune cells, and then participate in the regulation of immune responses and the immune evasion process of tumors (page 10, [0054]; page 39, [0214]). The specification also discloses that the present disclosure develops a targeting antibody that can bind to ITPRIPL1 with high affinity and neutralize its function (page 10, [0051]). The specification teaches the generation of polyclonal and monoclonal antibodies to ITPRIPL1, with ITPRIPL1-RBD (receptor binding domain) as an immunogen (pages 50-57, Example 6; pages 90-93, Example 19). The specification teaches that the capacity of binding to ITPRIPL1 varies among antibodies (indicating heterogeneity), with antibodies “13B7” and “18B12” as the antibodies with the best binding (page 92, [0403]; Figure 57; page 93, [0406]; Example 20; page 96, [0419]). The specification discloses that for monoclonal antibody, “13B7A6H3”, the heavy chain amino acid sequence is set forth in SEQ ID NO: 22; the light chain amino acid sequence is set forth in SEQ ID NO: 23; the heavy chain variable region (VH) amino acid sequence is set forth in SEQ ID NO: 24; and the light chain variable region (VL) amino acid sequence is set forth in SEQ ID NO: 25 (page 100, [0436]). For monoclonal antibody, “18B12D1A6”, the heavy chain amino acid sequence is set forth in SEQ ID NO: 32; the light chain amino acid sequence is set forth in SEQ ID NO: 33; the heavy chain variable region (VH) amino acid sequence is set forth in SEQ ID NO: 34; and the light chain variable region (VL) amino acid sequence is set forth in SEQ ID NO: 35 (pages 100-101, [0436]).
(i) Regarding instant claims 1, 7, and 12 and the phrases “regulating immune responses” and “regulating the functions of antigen presenting cells and T lymphocytes”, the specification teaches that the term “regulate” generally includes the meaning of upward or downward regulation in two different directions, which in some cases can be understood as inhibition of enhancement, in some cases can be understood as reduction or improvement, in some cases can be understood as decreasing or increasing, etc. (page 31, [0183]). However, in view of the Examples and teachings of the instant specification, the administered anti-ITPRIPL1 antibodies neutralize ITPRIPL1 and significantly increase the activity and infiltration of T cells in ITPRIPL1-overexpressed tumors (page 56, [0269]; page 57, [0270]; page 86, [0365]); and inhibit tumor cell growth in tumors overexpressing ITPRIPL1 (page 56, [0268]; page 57, [0271]; pages 65-66, Example 10; page 85, [0361]). There are no methods or working examples in the instant specification that indicate administration of an anti-ITPRIPL1 antibody regulates (i.e., inhibits or enhances) all possible immune responses. There are also no methods or working examples that indicate administration of an anti-ITPRIPL1 antibody regulates the functions of antigen presenting cells (APCs) during autoimmune responses; regulates transplant rejection-suppressing immune responses; regulates allergies; or regulates anti-infection immune responses, as required by instant claim 7. There are no methods or working examples that indicate administration of anti-ITPRIPL1 antibody regulates type I diabetes, immunologic fertility, rejection after organ transplantation, allergies, systemic inflammation or cytokine storm, or infection, as required by instant claim 8. The closest prior art of Mootha et al. (WO 2021/173712) teaches treating a subject with Fuchs’ endothelial corneal dystrophy (FECD), which is characterized by activation of the immune system, by administering one or more therapeutic agents, such as an antibody, that decrease the amount or expression of ITPRIPL1 (pages 3-4, [0011-0012]; page 95, [0480]; page 98, [0497]; page 99, [0502-0503]).
A large quantity of experimentation would be required of the skilled artisan to determine if an anti-ITPRIPL1 antibody has any effect on regulating all possible immune responses; regulating the functions of antigen presenting cells (APCs) during autoimmune responses; regulating transplant rejection-suppressing immune responses; regulating allergies; regulating anti-infection immune responses; regulating type I diabetes; regulating immunologic fertility; regulating rejection after organ transplantation; regulating systemic inflammation or cytokine storm; or regulating infection. Such experimentation is considered undue.
The skilled artisan also would not be able to predict that the findings of the instant specification would extend to such broad functions as recited in claims 1, 7, 8, and 12 because the instant specification teaches that “[t]here are no previous reports on the function of ITPRIPL1 gene” (page 33, [0189]). Deng et al. (Cell 187: 2305-2323, 2024) also state that ITPRIPL1 is a single-pass type I transmembrane protein with uncharacterized functions (page 2305, column 2, last paragraph). Additionally, the immune responses and autoimmune diseases/disorders encompassed by the claims are complex and have different pathophysiologies. One skilled in the art would not be able to predict from the teachings of the instant specification that an anti-ITPRIPL1 antibody would regulate an infinite number of immune responses and/or autoimmune diseases/disorders because such have different pathophysiologies, involve numerous different cell types, and may be recalcitrant to treatment. The disclosure in the specification is merely an invitation to the artisan to use the current invention as a starting point for further experimentation. For example, undue experimentation would be required of the skilled artisan to determine the dosage, route of administration, and duration of administration of an anti-ITPRIPL1 antibody to regulate all possible immune responses; regulate the functions of antigen presenting cells (APCs) during autoimmune responses; regulate transplant rejection-suppressing immune responses; regulate allergies; regulate anti-infection immune responses; regulate type I diabetes; regulate immunologic fertility; regulate rejection after organ transplantation; regulate systemic inflammation or cytokine storm; or regulate infection.
Applicant is reminded that the courts have stated that patent protection is granted in return for an enabling disclosure, not for vague intimations of general ideas that may or may not be patentable. Tossing out the mere germ of an idea does not constitute an enabling disclosure. Reasonable detail must be provided in order to enable members of the public to understand and carry out the invention. See Genentech v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 (1997). Furthermore, Applicant is reminded that a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. See In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971); In re Soll, 97 F.2d 623, 634, 38 USPQ 189, 191 (CCPA 1938; In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991).
Due to the large quantity of experimentation necessary to regulate all possible immune responses; regulate the functions of antigen presenting cells (APCs) during autoimmune responses; regulate transplant rejection-suppressing immune responses; regulate allergies; regulate anti-infection immune responses; regulate type I diabetes; regulate immunologic fertility; regulate rejection after organ transplantation; regulate systemic inflammation or cytokine storm; or regulate infection by administration of an anti-ITPRIPL1 antibody;; the lack of direction/guidance presented in the specification regarding the same;; the absence of working examples directed to the same;; the complex nature of the invention;; the state of the art (see Deng et al.);; the unpredictability of such regulating;; and the breadth of the claims, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
(ii) Regarding the recitation of “resisting tumors” and “anti-tumor immune responses” in claims 1, 7, and 12, the specification does not provide a specific definition or explanation for “resist/resisting tumors” or “anti-tumor responses”. As discussed under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph (above), it is not clear, for example, if “resisting tumors” encompass treating tumors, preventing tumors, or something else entirely.
The instant specification discloses that ITPRIPL1 is detected in cell lines from different types of tumors (pages 48-49, [0246-0247]; Figure 17; Example 18, pages 89-90). The Examples in the instant specification disclose that administered anti-ITPRIPL1 antibodies significantly increase the activity and infiltration of T cells in ITPRIPL1-overexpressed tumors (page 56, [0269]; page 57, [0270]; page 86, [0365]) and inhibit tumor cell growth in tumors overexpressing ITPRIPL1 (page 56, [0268]; page 57, [0271]; pages 65-66, Example 10; page 85, [0361]). Numerous post-filing date references also evidence that ITPRIPL1 is overexpressed in several different cancers and is correlated with tumor stage (see Deng et al., Front Cell Dev Biol 11: 1297211, 2023; Duan et al., Front Mol Biosci 11: 1452290, 2024; Jia et al., J Gastroenterol Hepatol 41: 231-247, 2026; Wang et al., Sci Reports 15: 42204, 2025; Wang et al., Cancers 13: 1375, 2021; Zou et al., Brain and Behavior 15: e70762, 2025).
First, there are no methods or working examples that indicate treatment of all possible tumors or regulation of all anti-tumor immune responses by administration of an anti-ITPRIPL1 antibody. Again, the specification is only enabling for a method of treating a cancer or tumor that overexpresses ITPRIPL1. Undue experimentation would be required of the skilled artisan to determine a nexus between ITPRIPL1 and all possible tumors and tumor immune responses and then administer an anti-ITPRIPL1 antibody. One skilled in the art would also not be able to predict that an anti-ITPRIPL1 antibody would treat all possible tumors because Duan et al. actually teach that high ITPRIPL1 expression is associated with a better prognosis in breast cancer (BRCA) patients (supra; abstract). Duan et al. also disclose that ITPRIPL1 expression is significantly reduced in BRCA, prostate adenocarcinoma, and testicular germ cell tumors (page 3, column 2, 2nd full paragraph). Therefore, one skilled in the art would not want to inhibit ITPRIPL1 in these cancers that already have a reduction in ITPRIPL1. Duan et al. also conclude that future research is necessary to fully elucidate the role of ITPRIPL1 in cancer biology and therapy (page 9, column 2).
Second, in view of the lack of a definition for “resisting tumors” in the instant specification, one alternative of such phrase is interpreted by the Examiner as meaning “preventing tumors”, i.e. tumors will not occur. However, the specification does not teach any methods or working examples that indicate prevention of all possible tumors by administration of an anti-ITPRIPL1 antibody. At the time of filing the instant application, one skilled in the art would also not be able to predict that administration of an anti-ITPRIPL1 antibody would prevent all possible tumors. The limited teachings of the specification are not adequate guidance, but are merely an invitation for the artisan to use the current invention as a starting point for further experimentation. For instance, the prior art discloses that cancer prevention is complex and has had limited success (White et al., J Adolescent Health 52: S1-S7, 2013; page S2; page S5, column 1, 2nd full paragraph). White et al. teach that cancer is the result of multiple alterations in processes that control cell proliferation, invasion, and spread (page S2, column 1, 1st full paragraph). White et al. continue to disclose that nearly all cancers result from multiple factors that influence these processes over an extended time, such factors including genetic mutations, environmental interactions, and lifestyle (page S2, column 1, 1st full paragraph).
Undue experimentation would be required of the skilled artisan to determine the optimal quantity and duration of administration of an anti-ITPRIPL1 antibody for prevention of all possible tumors. The limited guidance in the specification is not adequate and is merely an invitation to the artisan to use the current invention as a starting point for further experimentation. Such trial and error experimentation is considered undue. Furthermore, Applicant is reminded that a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. See In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971); In re Soll, 97 F.2d 623, 634, 38 USPQ 189, 191 (CCPA 1938; In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). The present invention is unpredictable and complex wherein one skilled in the art may not necessarily prevent all possible tumors by administration of an anti-ITPRIPL1 antibody.
Due to the large quantity of experimentation necessary to treat all possible tumors, regulate all anti-tumor immune responses, and prevent all tumors by administration of an anti-ITPRIPL1 antibody; the lack of direction/guidance presented in the specification regarding the same; the absence of working examples directed to the same; the complex nature of the invention; the unpredictability of treating all possible tumors, regulating all anti-tumor immune responses, and preventing all tumors; and the breadth of the claims, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
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.
8. Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Mootha et al. (WO 2021/173712; published 02 September 2021; priority to 24 February 2020).
Mootha et al. teach treating a subject with Fuchs’ endothelial corneal dystrophy (FECD) comprising administering one or more therapeutic agents that decrease the amount or expression of ITPRIPL1 (pages 3-4, [0011-0012]). Mootha et al. also indicate that FECD subjects are characterized by activation of the immune system, meeting the limitations of instant claim 1 (page 95, [0480]; page 98, [0497]; page 99, [0502-0503]). Mootha et al. disclose that the administered therapeutic agent can be an antibody, meeting the limitations of instant claims 1 and 2 (page 4, [0012]). Mootha et al. teach that the antibody may be monoclonal, polyclonal, heterospecific, polyspecific, or single-chain, meeting the limitations of instant claim 3 (page 42, [0291]).
Applicant cannot rely upon a certified copy of the foreign priority application CN 202011191447.2 (30 October 2020) to overcome the rejection under 35 U.S.C. 102(a)(1) because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Conclusion
No claims are allowable.
The art made of record and not relied upon is considered pertinent to applicant's disclosure:
Deng et al. Cell 187: 2305-2323, 2024 (teach ITPRIPL1 is an inhibitory ligand of CD3ε; ITPRIPL1 expression inhibits T cells in the tumor microenvironment; treating with a neutralizing antibody decreases tumor growth and promotes T cell infiltration)
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BEB
Art Unit 1647
14 April 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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