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 .
1. The Amendment filed June 4, 2026 in response to the Office Action of February 19, 2026, is acknowledged and has been entered. Claims 10, 14-25, 28-34 are now pending and being examined. Claims 10, 23, 24, 28 are amended. Claims 33 and 34 are new.
Claim Objections
2. Claims 15-17 and 34 are free of the art but are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Maintained Rejections
(amendments addressed)
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.
3. Claims 23-25 and 29-32 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a method for treating cancer in a subject in need thereof, comprising administering to the subject an agent comprising an anti-TCTP antibody, wherein the agent functions to:
suppress or inhibit binding between TCTP and TLR2 (claim 1);
treat cancer (claim 1); and
inhibit accumulation of myeloid-derived suppressor cells (MDSCs) in tumor microenvironment (TME) (claim 24).
Thus, the claims identify the agent comprising the anti-TCTP antibody by function only. No agent or antibody structure is recited. The agent comprising the anti-TCTP antibody is critical to performing the claimed method.
The instant published specification discloses:
[0065] Examples of the substance that suppresses or inhibits the function of TCTP may include, but are not particularly limited to: antibodies, peptide aptamers, and the like that suppress or inhibit the function of TCTP; substances that decompose TCTP or induce decomposition of TCTP, such as, for example, dihydroartemisinin (DHA) and Sertraline; and substances that suppress or inhibit the expression of TCTP, such as, for example, siRNA and miRNA. Further examples of the substance that suppresses or inhibits the function of TCTP may also include substances that inhibit the binding of TCTP to a receptor thereof (TLR2), such as, for example, a TLR2 antagonist. This inhibitory substance may be a substance that interacts with TCTP or a receptor thereof (TLR2), or decomposes any one of them.
[0066] The inhibitor according to the present embodiment may comprise the above-described substance that suppresses or inhibits the function of TCTP.
[0067] A second embodiment of the present invention relates to an antibody that suppresses or inhibits the function of TCTP (hereinafter also referred to as “the anti-TCTP antibody according to the present embodiment”).
[0068] The “antibody” used in the present description is not particularly limited in terms of a preparation method thereof and a structure thereof, and examples of the present antibody may include all “antibodies” that each bind to a desired antigen based on desired properties, such as, for example, a monoclonal antibody, a polyclonal antibody, or a nanoantibody.
Thus, the instant specification discloses that the genus of claimed agents, or substances, that suppress or inhibit the function of TCTP is vast and may include, but are not particularly limited to: antibodies, peptide aptamers, and the like that suppress or inhibit the function of TCTP; substances that decompose TCTP or induce decomposition of TCTP, such as, for example, dihydroartemisinin (DHA) and Sertraline; and substances that suppress or inhibit the expression of TCTP, such as, for example, siRNA and miRNA. Substances that suppresses or inhibits the function of TCTP may also include substances that inhibit the binding of TCTP to a receptor thereof (TLR2), such as, for example, a TLR2 antagonist. The substance may be a substance that interacts with TCTP or a receptor thereof (TLR2), or decomposes any one of them.
With regard to anti-TCTP antibodies, the instant specification discloses three exemplary anti-TCTP mouse monoclonal antibodies 55F3, 44E1, and 51A9 that comprise the CDRs, VH, and VL sequences recited in instant claims 14-17 (see [87-107]; Example 1-18). The instant specification demonstrates in the Examples section 5, that the chemical DHA, and antibodies 55F3, 44E1, and 51A9 have anti-tumor activity.
Thus, the instant specification describes only three exemplary structurally distinct anti-TCTP monoclonal antibodies that function as claimed. Outside the genus of antibodies (i.e., agents), the instant specification discloses identifiable chemicals dihydroartemisinin (DHA) and sertraline as exemplary agents that suppress or inhibit the function of TCTP. The specification fails to disclose any other structure/sequence required of an anti-TCTP antibody or agent comprising the antibody to possess the functions claimed and listed above.
To provide adequate written description and evidence of possession of the claimed antibody and agent genus required to practice the method, the instant specification can structurally describe representative agents and antibodies that function as claimed and listed above, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for antibodies that bind TCTP, inhibit binding between TCTP and TLR2, treat cancer, and inhibit accumulation of MDSCs in tumor immune microenvironment, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future agents or antibodies yet to be discovered that may function as claimed. The TCTP antigen and its receptors (TLR2) provide no information about the structure of an antibody that binds to TCTP, inhibits binding between TCTP and TLR2, treats cancer, and inhibits accumulation of MDSCs in tumor immune microenvironment.
In this case, the only factor present in the claims is a recitation of the antibody or agent function as listed above. The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification discloses only three exemplary monoclonal antibody sequences and two known chemicals that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody or agent does, rather than what it is. Other than for three defined monoclonal antibody sequences and two known chemical structures, the specification fails to provide the structural features coupled to the claimed functional characteristics for one to immediately envision members of the genus of agents required to practice the invention. The instant specification fails to describe a representative number of antibody sequences and agent structures for the genus of antibodies and agents that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to perform the claimed method.
With regard to the anti-TCTP antibody genus required to practice the invention, the specification discloses only three mouse monoclonal anti-TCTP antibodies that function as claimed, each antibody comprising six defined CDR SEQ ID NOs from the heavy and light chains that are critical to performing the claimed functions listed above. The specification does not disclose the sequence structure of any other antibodies that would predictably function as claimed. The claims broadly encompass any anti-TCTP antibody that functions as claimed and listed above. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the variable domains or CDRs that can be altered and still maintain TCTP binding function and suppress/inhibit the function of TCTP, treat cancer, and inhibit accumulation of MDSCs in the TME. The instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses only three exemplary species of anti-TCTP antibody that function as claimed. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention. Therefore, one could not readily envision members of the broadly claimed genus required to practice the claimed invention.
Given the lack of representative examples to support the full scope of the claimed antibodies and agents used in the claimed method, and lack of reasonable structure-function correlation with regards to the unknown sequences/structures of antibodies and agents that perform the claimed functions, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of agents and anti-TCTP antibodies that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner Suggestion: Amend claim 23 to recite administering structurally identifiable anti-TCTP antibodies that are correlated to the claimed functions, for example:
Claim 23. A method of treating cancer in a subject in need thereof, comprising administering to the subject an anti-TCTP antibody comprising:
a) a heavy chain variable domain (VH) that comprises a heavy chain complementarity-determining region (HCDR) 1 comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, and a light chain variable domain (VL) that comprises a light chain complementarity-determining region (LCDR) 1 comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6,
b) a VH that comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 7, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 8, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 9, and a VL that comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12, or
c) a VH that comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 13, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 14, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 15, and a VL that comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 16, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 17, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 18.
Response to Arguments
4. Applicants argued that claim 23 is amended to recite anti-TCTP antibody or antigen-binding fragment thereof. Applicants argue that they discovered for the first time that TCTP, released from dying tumor cells, drives polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) accumulation in the tumor immune microenvironment (TIME) through a sequential signaling pathway. Specifically, TCTP activates TLR2, leading to induction of CXCL1/2, which in turn recruits PMN-MDSCs into the TIME. Applicants argue the specification as filed demonstrates that blocking extracellular TCTP suppresses tumor growth in vivo. The target (TCTP), the receptor (TLR2) TCTP signals through, the downstream effectors (CXCL1/2), and the in vivo therapeutic outcome were all fully characterized and disclosed in the specification as filed. Applicants argue the specification includes TCTP gene knock-out (KO) data demonstrating that complete depletion of TCTP from tumor cells, a different means of abrogating TCTP function, produced the same set of therapeutic effects: suppression of in vivo tumor growth, reduction of PMN-MDSC accumulation in the TIME, and enhancement of CD8⁻ T cell and NK cell activities (see, e.g., Figs. 2(c)-(e), 6(d)-(e), 7(a)-(c), and 8(a)). Applicants argue their data established that it is the suppression or inhibition of extracellular TCTP function, per se, that underlies the therapeutic effects; and these effects can be achieved by inhibitory molecules of distinct features.
Applicants argue that a POSITA can reasonably predict that an antibody or antigen-binding fragment thereof that suppresses or inhibits binding between TCTP and TLR2 can be used to treat cancer by suppressing tumor growth in vivo. Applicants argue that the specification discloses three anti-TCTP monoclonal antibodies, i.e., 55F3, 44E1, and 51A9, with the following structural and functional information: (i) complementarity determining region (CDR) sequences (SEQ ID NOs: 1-18); (ii) heavy and light chain variable region sequences (SEQ ID NOs: 19-24); (iii) a defined immunizing epitope (SEQ ID NO: 25, the C- terminal peptide of human TCTP); and (iv) demonstrated in vitro and in vivo functional activities, including inhibition of Cxcl1 mRNA induction in peritoneal exudate cells (PECs), reduction of PMN-MDSC accumulation in the TIME, and suppression of tumor growth in vivo (Figs. 12(a)-(b) and 13(a)-(e)). Applicants argue that these three structurally defined antibodies, all raised against the same defined epitope and shown to operate through the same mechanistic pathway, constitute representative species supporting the currently claimed genus. When considered together with the TCTP KO data described above, Applicant's disclosure as a whole makes clear that the observed therapeutic effects result from blocking extracellular TCTP function, a property shared by antibodies capable of binding and neutralizing TCTP.
Applicants argue the specification discloses features of the currently claimed antibody or antigen-binding fragment thereof, namely, that it must bind to extracellular TCTP, preferably at or near the defined C-terminal epitope (SEQ ID NO: 25), and thereby block TCTP's interaction with TLR2. Applicants argue that a POSITA would further be able to verify whether a given antibody falls within the claimed genus without undue experimentation, using the functional screening assays described in the specification (paragraph [0068]). Applicants argue that the TCTP KO data provide a POSITA with a clear and objective benchmark: any antibody or antigen-binding fragment thereof that reduces PMN-MDSC accumulation in the TIME, enhances CD8⁺ T cell and NK cell activities, and suppresses tumor growth, for example, one that reproduces the effects observed upon genetic depletion of TCTP, would predictably achieve the same therapeutic outcome and would be recognized as falling within the claimed genus. Applicants argue the specification as filed provides sufficient preparation and screening guidance. Specifically, the specification details: immunization of BALB/c mice with the defined C- terminal peptide of human TCTP (SEQ ID NO: 25) (paragraph [0068]); hybridoma screening by immunoblotting and immunoprecipitation to select antibodies that bind TCTP and suppress its immunomodulatory activity (paragraph [0068]); methods for generating humanized, chimeric, and recombinant antibodies (paragraphs [0017]-[0018]); recombinant antibody production by phage display and other methods (paragraph [0015]); and competitive binding assays to identify antibodies binding the same or overlapping epitope (paragraph [0033]).
Applicants argue that at the time of filing, generating monoclonal antibodies against a defined 20-amino acid peptide epitope was entirely routine for a POSITA. Applicants argue that this combination of a defined antigen sequence, established screening assays, and detailed preparation methods provides a POSITA with all the tools necessary to generate and identify additional antibodies within the claimed genus without undue experimentation. Applicants argue that the TCTP KO data further confirm that the functional outcome of any such antibody or antigen-binding fragment thereof is readily predictable from the specification: a POSITA would have a reasonable expectation that an antibody or antigen-binding fragment thereof capable of binding and neutralizing extracellular TCTP at the defined epitope would produce the same therapeutic effects as those observed upon genetic knock-out of TCTP, without the need for undue experimentation.
Applicants argue that the specification as filed reasonably conveys possession of the claimed genus of anti-TCTP antibodies and antigen-binding fragments thereof and fully satisfies the written description requirement under 35 U.S.C. § 112(a).
5. The arguments have been carefully considered but are not persuasive. Examiner relied upon the precedential decisions in University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) (“Lilly”) and Enzo Biochem, Inc. V. Gen-Probe Inc. (Fed. Cir. 2002) (“Enzo”) as the standards for determining adequate written description of the instant claims. Examiner established that:
the agent comprising the anti-TCTP antibody is critical to practicing the claimed method;
the claims identify the agent comprising the anti-TCTP antibody by function only without any identifiable sequence structure recited;
the specification fails to provide the critical or shared core structure correlated to, and responsible for, the agent/anti-TCTP antibody to function as claimed in order for a POSITA to recognize members of the agent/anti-TCTP antibody genus that would function in the method as claimed; and
the specification fails to provide a representative number of species of agents comprising anti-TCTP antibodies for the vast genus required to function as claimed, because the specification only discloses the sequences of 3 structurally distinct anti-TCTP antibodies.
In their arguments, Applicants only pointed to the same three anti-TCTP antibodies (55F3, 44E1, and 51A9) as exemplary species that were stated as the exemplary species in the rejection of record. Applicants have not persuasively argued these three antibodies are representative of the vast genus of anti-TCTP antibodies required to function as claimed, that would allow a POSITA to immediately recognize members of the genus that would function as claimed.
MPEP 2163 states:
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed."
In the instant case, the genus of anti-TCTP antibodies required to practice the claimed method of cancer treatment is vast, encompassing highly variable antibody CDR sequences critical to performing the claimed functions, and 3 anti-TCTP antibody species are not adequately representative of the vast genus.
MPEP 2163 states:
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that inventor was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49, stating that "if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function".). "Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function." Id.
In the instant case, other than for the three anti-TCTP antibodies 55F3, 44E1, and 51A9, the instant specification does not disclose any sufficiently detailed, relevant identifying characteristics which provide evidence that inventor was in possession of the claimed anti-TCTP antibody genus required to practice the invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Based on the disclosure of only three structurally distinct monoclonal anti-TCTP antibodies 55F3, 44E1, and 51A9 that function as claimed, a POSITA could not immediately recognize or envision which anti-TCTP antibodies in the universe of anti-TCTP antibodies would function to inhibit binding between TCTP and TLR2, treat cancer, and inhibit accumulation of MDSCs in tumor immune microenvironment. A skilled artisan would NOT have understood the inventor to be in possession of the claimed invention at the time of filing.
Contrary to arguments, knowledge of methods for the routine production and screening of antibodies binding to TCTP does not place Applicants in possession of the vast genus of anti-TCTP antibodies required to inhibit binding between TCTP and TLR2, treat cancer, and inhibit accumulation of MDSCs in tumor immune microenvironment. As stated in the rejection:
Although Applicants may argue that it is possible to screen for antibodies that bind TCTP, inhibit binding between TCTP and TLR2, treat cancer, and inhibit accumulation of MDSCs in tumor immune microenvironment, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future agents or antibodies yet to be discovered that may function as claimed. The TCTP antigen and its receptors (TLR2) provide no information about the structure of an antibody that binds to TCTP, inhibits binding between TCTP and TLR2, treats cancer, and inhibits accumulation of MDSCs in tumor immune microenvironment.
Finally, although Applicants argue they are enabled to make and screen for anti-TCTP antibodies that function as claimed, this capability does not place Applicants in possession of the vast genus of anti-TCTP antibodies required to practice the claimed invention. Knowledge of screening methods provides no information about the identifying sequence structure of any future antibodies yet to be discovered that may function as claimed. The TCTP antigen and its receptors (TLR2) provide no information about the structure of an antibody that binds to TCTP, inhibits binding between TCTP and TLR2, treats cancer, and inhibits accumulation of MDSCs in tumor immune microenvironment.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
6. Claims 10, 14, 18-25, 28-33 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,329,814; in view of Bommer et al (Cell Communication and Signaling, 2017, 15:9, internet pages 1-15). Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patent is claiming overlapping methods of treating the same cancer with an anti-TCTP antibody comprising the same CDR sequences instantly claimed, and in combination with anti-PD-1 antibody.
The US Patent claims:
1. A method for treating cancer in a patient in need thereof, comprising administering a combination comprising (1) a substance that suppresses or inhibits a function of extracellular translationally controlled tumor protein (TCTP) or its modified form, or a fragment or multimer thereof and (2) a cancer immunotherapeutic agent, to the patient,
wherein the substance that suppresses or inhibits the function of extracellular TCTP or its modified form, or a fragment or multimer thereof is an antibody or antigen-binding fragment thereof which specifically binds to TCTP or its modified form, or a fragment or multimer thereof, and the extracellular TCTP or its modified form, or a fragment or multimer thereof has been released from tumor cells,
wherein the cancer immunotherapeutic agent is an immune checkpoint inhibitor selected from an anti-PD-1 antibody and anti-CTLA-4 antibody, and
wherein the antibody or antigen-binding fragment thereof, which specifically binds to TCTP or its modified form, or a fragment or multimer thereof, and the extracellular TCTP or its modified form, or a fragment or multimer thereof, comprises complementarity-determining region (CDR)-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 selected from the group consisting of the following:
a) CDR-H1 of the sequence of SEQ ID NO: 1, CDR-H2 of the sequence of SEQ ID NO: 2, CDR-H3 of the sequence of SEQ ID NO: 3; CDR-L1 of the sequence of SEQ ID NO: 4, CDR-L2 of the sequence of SEQ ID NO: 5, and CDR-L3 of the sequence of SEQ ID NO: 6;
b) CDR-H1 of the sequence of SEQ ID NO: 7, CDR-H2 of the sequence of SEQ ID NO: 8, CDR-H3 of the sequence of SEQ ID NO: 9; CDR-L1 of the sequence of SEQ ID NO: 10, CDR-L2 of the sequence of SEQ ID NO: 11, and CDR-L3 of the sequence of SEQ ID NO: 12;
c) CDR-H1 of the sequence of SEQ ID NO: 13, CDR-H2 of the sequence of SEQ ID NO: 14, CDR-H3 of the sequence of SEQ ID NO: 15; CDR-L1 of the sequence of SEQ ID NO: 16, CDR-L2 of the sequence of SEQ ID NO: 17, and CDR-L3 of the sequence of SEQ ID NO: 18; and
d) CDR-H1 of the sequence of SEQ ID NO: 19, CDR-H2 of the sequence of SEQ ID NO: 20, CDR-H3 of the sequence of SEQ ID NO: 21; CDR-L1 of the sequence of SEQ ID NO: 22, CDR-L2 of the sequence of SEQ ID NO: 23, and CDR-L3 of the sequence of SEQ ID NO: 24.
2. The method according to claim 1, wherein the cancer is selected from the group consisting of colorectal cancer, melanoma, and fibrosarcoma.
3. The method according to claim 1, wherein the substance that suppresses or inhibits the function of extracellular TCTP or its modified form, or a fragment or multimer thereof alleviates, reverts or prevents immune suppression in the tumor immune microenvironment.
4. The method according to claim 1, wherein the substance that suppresses or inhibits the function of extracellular TCTP or its modified form, or a fragment or multimer thereof activates or enhances the functions of T cells and/or NK cells.
5. The method according to claim 1, wherein the substance that suppresses or inhibits the function of extracellular TCTP or its modified form, or a fragment or multimer thereof functions as an antagonist of myeloid-derived suppressor cells (MDSCs) in the tumor immune microenvironment.
6. The method according to claim 1, wherein the patient has shown or is likely to show no or limited response to immunotherapy for the treatment of cancer.
7. The method according to claim 1, wherein (1) the substance that suppresses or inhibits the function of extracellular TCTP or a modified form, or fragment or multimer thereof and (2) the cancer immunotherapeutic agent are administered simultaneously or sequentially.
8. The method according to claim 1, wherein the substance that suppresses or inhibits the function of extracellular TCTP or its modified form, or a fragment or multimer thereof, competitively inhibits binding of an anti-TCTP antibody to TCTP, wherein said anti-TCTP antibody comprises CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 selected from the group consisting of the following:
a) CDR-H1 of the sequence of SEQ ID NO: 1, CDR-H2 of the sequence of SEQ ID NO: 2, CDR-H3 of the sequence of SEQ ID NO: 3; CDR-L1 of the sequence of SEQ ID NO: 4, CDR-L2 of the sequence of SEQ ID NO: 5, and CDR-L3 of the sequence of SEQ ID NO: 6;
b) CDR-H1 of the sequence of SEQ ID NO: 7, CDR-H2 of the sequence of SEQ ID NO: 8, CDR-H3 of the sequence of SEQ ID NO: 9; CDR-L1 of the sequence of SEQ ID NO: 10, CDR-L2 of the sequence of SEQ ID NO: 11, and CDR-L3 of the sequence of SEQ ID NO: 12;
c) CDR-H1 of the sequence of SEQ ID NO: 13, CDR-H2 of the sequence of SEQ ID NO: 14, CDR-H3 of the sequence of SEQ ID NO: 15; CDR-L3 of the sequence of SEQ ID NO: 16, CDR-L2 of the sequence of SEQ ID NO: 17, and CDR-L3 of the sequence of SEQ ID NO: 18; and d) CDR-H1 of the sequence of SEQ ID NO: 19, CDR-H2 of the sequence of SEQ ID NO: 20, CDR-H3 of the sequence of SEQ ID NO: 21; CDR-L1 of the sequence of SEQ ID NO: 22, CDR-L2 of the sequence of SEQ ID NO: 23, and CDR-L3 of the sequence of SEQ ID NO: 24.
The US Patent claims reciting a pharmaceutical use of the anti-TCTP antibody or antigen-binding fragment thereof, and recites its CDR sequences, rendering obvious the instant anti-TCTP antibody of claims 10, 14, 18-22 comprising the same CDRs and comprised in a pharmaceutical composition.
With regard to claims 30 and 31, the US Patent does not claim further testing the colorectal cancer patient tissue for levels of TCTP protein expression.
Bommer teaches TCTP is a biomarker of CRC. TCTP is an anti-apoptotic protein frequently overexpressed in cancers, where high levels are often associated with poor patient outcome. TCTP may be involved in protecting cancer cells against the cytotoxic action of anti-cancer drugs. Bommer demonstrates detecting the early increase of TCTP levels in human colorectal cancer (CRC) and the regulation of TCTP expression in HCT116 colon cancer cells, in response to treatment with the anti-cancer drugs 5-FU and oxaliplatin. Bommer measured levels of TCTP protein in CRC patient tumor tissue samples and normal tissue utilizing immunohistochemistry. Bommer identified TCTP as a biomarker that is significantly increased in CRC compared to normal colon tissue, and increased significantly in early stages of CRC development. Bommer concludes that increased TCTP levels in CRC contribute to chemotherapy resistance to 5-FU/oxaliplatin treatment. Bommer suggests measuring levels of TCTP in CRC patients to monitor and prevent development of drug resistance (abstract; Discussion, Conclusion). Bommer established TCTP protein expression is a biomarker of CRC progression and drug resistance, suggesting assessing the biomarker to determined cancer progression and drug resistance.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to additionally test for TCTP levels in the CRC patients treated by the method of the US Patent. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Bommer established TCTP is a biomarker for the development and presence of CRC and for the resistance to therapy; (2) Bommer suggests measuring TCTP in CRC patients in order assess CRC status and drug resistance; and (3) Bommer demonstrates successfully detecting protein levels of TCTP in CRC patient tumor tissues.
It is noted that the US Patent claims do not recite or render obvious the full VH and VL sequences of the anti-TCTP antibodies instantly claimed, and the VH and VL sequences are not obviated by prior art, therefore claims 15-17 are not rejected.
Response to Arguments
7. Applicants argue U.S. Patent No. 12,329,814 has a later effective filing date (6/30/2022) than that of the instant application, therefore cannot serve as a proper OTDP references against the present application which claims an earlier effective filing date. Applicants point to the Uruguay Round Agreement Act of 1994 to support their arguments on p. 16-19 of their Remarks.
Applicants argue that since the instant application has an earlier claimed filing date (06/21/2021) than the reference patent (06/30/2022), the 20-year statutory term under 35 U.S.C. § 154(a)(2) of any patent that issues from the instant application will expire earlier than the 20 year statutory term of the reference patent. Applicants argue there is no improper time-wise extension of the term of any patent that issues from this application based on the later-filed reference patent.
Applicants argue that MPEP states, "If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent." See Manual of Patent Examining and Procedure § 804.I.B.1.(b)(i).
8. The arguments have been carefully considered but are not persuasive. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to:
(A) prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent; and to
(B) prevent possible harassment by multiple assignees.
Applicant’s arguments are direct toward (A) above. Contrary to arguments, the patent expiration date of the instant application, if/when issuing to patent, is not yet determined due to the possibilities of patent term extension or patent term adjustment that have yet to be determined. Therefore, Applicants have not persuasively argued that the instant application patent term will expire before the non-family member patents that had later effective filing dates.
Applicants appear to be arguing conditions to drop a provisional obviousness double patenting rejection over a reference patent application (not a US Patent) when it is the only remaining rejection, and the reference application has a later effective filing date. See MPEP 804 (b)(i). This is not the case here, because the remaining double patenting rejection is NOT provisional, and is made over a US Patent. Therefore, the double patenting rejection is maintained to prevent the unjustified or improper timewise extension of the right to exclude granted by a patent.
Finally, with regard to (B) above, the double patenting rejection is maintained to prevent possible harassment by multiple assignees, given the overlapping claimed subject matter that renders the instant claims obvious.
9. All other objections and rejections recited in the Office Action mailed February 19, 2026 are hereby withdrawn in view of amendments. The rejection of claims under 35 U.S.C. 102(a)(1) as being anticipated by WO 2012080509, Rochhi et al, is withdrawn in view of amendments to claim 23 requiring administration of an anti-TCTP antibody that functions to inhibit TCTP binding to TLR2. Rochhi teaches their antagonistic anti-TCTP antibodies function to inhibit binding to hsp27, and do not teach the antibodies inhibit binding to TLR2. The rejection of claims under 35 U.S.C. 102(a)(1) and 35 U.S.C. as being anticipated and obvious over Duan et al (2019) are withdrawn in view of amendments to claim 23 requiring administration of an anti-TCTP antibody, which Duan does not teach.
10. Conclusion: Claims 15-17 and 34 are objected to. Claims 10, 14, 18-25, 28-33 are rejected.
Conclusion
11. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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/Laura B Goddard/Primary Examiner, Art Unit 1642
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