Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/29/2026 has been entered.
3. Claims 16 and 21-38 are pending.
4. Claims 29-32 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group and claim 25 stands withdrawn as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/12/2025.
5. Claims 16, 21-24, 26-28 and 33-38 are currently under consideration as they read on the full scope of the claims.
Claim Objections
6. Claim 36 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 35. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
7. Claim 27-28 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of peptides and nucleic acids encoding polypeptides is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: peptides and nucleic acids are not functionally equivalent, do not have a common use, have distinct structures and are not belonging to the same chemical class.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
8. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
9. Claims 16, 23-24, 26-28 and 33-34 are rejected under 35 U.S.C. 101 because the claimed invention is directed to many naturally occurring polypeptides. SEQ ID NOs 6, 7, 9-13 and 15-20, 35, 64-65 and 67 are all peptides of naturally occurring proteins. At least the polypeptides comprising SEQ ID NOs 6, 7, 9-13 and 15-20, 35, 64-65 and 67 read on full length naturally occurring proteins. For example, as evidenced by Figure 4d in Thabault et al. (PTO-892 mailed on 06/18/2025; Reference U), naturally occurring lactate dehydrogenase from Homo sapiens comprises instant SEQ ID NOs:6-7 and 65. This judicial exception is not integrated into a practical application because the claims fail to recite additional elements which would integrate the judicial exception into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements of a pharmaceutical composition, kit and medicaments comprising a pharmaceutically acceptable vehicle which reads on water and does not add significantly more (also known as an “inventive concept”) to the exception.
As such, claims 16, 23-24, 26-28 and 33-34 are not directed to patentable subject matter.
Applicant’s arguments filed on 04/29/2026 have been fully considered, but are not found persuasive.
Applicant argues:
“The Office Action rejected claims 16, 23, 24, 26-28, 33, and 34 under 35 U.S.C. § 101 as allegedly directed to naturally occurring polypeptides.
The claim pertains to a polypeptide being an isolated polypeptide consisting of 8 to 30 amino acids, comprising the recited sequences. Such peptides are not found in nature.
The inventors have determined "hot spots" in the lactate dehydrogenase (LDH) enzyme that served as a base for the design of peptides aimed at inhibiting the tetramerization of LDH (and thus, its function).
The Examiner's allegation that peptide fragments "have no properties when isolated from the naturally occurring protein that the peptides do not have within the context of the naturally occurring protein" is incorrect.
The naturally occurring LDH catalyzes the reversible conversion of pyruvate to lactate; on the contrary, the claimed peptides inhibit the tetramerization of LDH and are utterly uncapable of catalyzing the reversible conversion of pyruvate to lactate.
The properties of the naturally occurring protein and the claimed fragments are not merely different; they are opposite.
Furthermore, the size of the fragment is relevant when put into practice. LDH is a large protein that is not suitable for human administration; on the contrary, the claimed fragments are adapted for such purpose and have increased stability.
It is thus obvious to the person skilled in the art that the claimed peptide are suitable for human administration for inhibiting the function of LDH, while the naturally occurring protein does not enable this effect.
Accordingly, Applicant respectfully requests withdrawal of these rejections.”
It is the Examiner’s position that Applicant’s arguments are not persuasive as they read on the linear peptides. Peptide fragments of naturally occurring polypeptides, as discussed supra, are not patent eligible because they have no properties when isolated from the naturally occurring protein that the peptides do not have within the context of the naturally occurring protein. The sequence of the peptide is the same.
Applicant’s argument that a fragment of LDH does not have the same function as full length LDH is not persuasive. Applicant’s argument that the properties of the naturally occurring protein and the claimed fragments are not merely different; they are opposite is unpersuasive.
Applicant’s argument that the peptides have a function that cannot be ascribed to the full length polypeptide is not persuasive. As detailed in the 112, first paragraph rejection, the specification has not demonstrated that the claimed peptides have the recited function. So, the function is not demonstrated to be opposite that of the full length polypeptide.
Applicant’s argument that LDH is a large protein that is not suitable for human administration; on the contrary, the claimed fragments are adapted for such purpose and have increased stability is not persuasive. Being able to be injected in vivo is not a sufficient difference because any peptide or polypeptide can be injected into a subject and there is no evidence of record that the effect exerted by the peptide would be any different than that of the full length polypeptide. The arguments of counsel cannot take the place of evidence in the record. In re Schulze , 145 USPQ 716, 718 (CCPA 1965). See MPEP 716.01.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements of a pharmaceutical composition, kit and medicaments comprising a pharmaceutically acceptable vehicle which reads on water and does not add significantly more (also known as an “inventive concept”) to the exception.
Claims 16, 23-24, 26-28 and 33-34 are not directed to patentable subject matter
10. 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.
11. Claims 16 and 27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for: the peptide consisting of SEQ ID NO:61 which inhibits tetramerization of the lactate dehydrogenase subunits; and the peptides of SEQ ID NOs 6-22, 30-35, 55-58, 61-65 and 67-68 without any specified function and compositions and kits thereof; does not reasonably provide enablement for a kits for preventing cancer comprising a polypeptide comprising the amino acid sequence of SEQ ID NO:6-7, 9-13, 15-20, 30-35, 55-58, 61-65 and 67-68.
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. The specification disclosure does not enable one skilled in the art to practice the invention without an undue amount of experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The claims encompass polypeptides which do not inhibit tetramerization of the lactate dehydrogenase subunits. The skilled artisan cannot make and use the peptides commensurate in scope with the claims.
The claimed linear sequences comprising SEQ ID NOs:6-20 encompass an enormous number of polypeptides. In addition to each of the 8-19 amino acids in SEQ ID NOs:6-20, the peptides may comprise up to 11-22 additional amino acids added onto the N- and/or C-terminus of the peptide. Furthermore, SEQ ID Nos 18-20 comprise variable amino acids within the recited sequences. In the same way, cyclic peptides 67 and 68 comprise a variable amino acid each.
The art of Thabault et al. (PTO-892 mailed on 06/18/2025; Reference U) teaches many of the peptides encompassed by the claimed invention do not inhibit tetramerization of the lactate dehydrogenase subunits . The reference teaches that only one peptide, “macrocyclic peptide 7” of Table 3 (CTLKCKLI p-tetrafluorophenyl linker) was able to inhibit the tetramerization of the lactate dehydrogenase subunits. (In particular, Figure 9, whole document). As such one of ordinary skill in the art would be required to perform undue experimentation to make and use the invention commensurate in scope with the claims.
The specification does not provide sufficient guidance on how to a kit comprising the claimed peptides can be used as a type of vaccine to sufficiently prevent cancer. The first criterion in judging a vaccine is the level of antibody (humoral immune response) before and after immunization. The success of the vaccination is judged by the extent of increase in the level of antigen - specific antibody. The second criterion for a vaccine is its ability to stimulate memory T lymphocytes (cell-mediated immune response) (See Kuby; PTO-892; Reference U). As such one of ordinary skill in the art would be required to perform undue experimentation to make and use the recited genus of kits for preventing cancer.
Zhou et al. (PTO-892; Reference V) teaches that “numerous cancer vaccines have progressed to clinical evaluation, demonstrating the ability to elicit strong immune responses. However, despite some early successes, the majority have not achieved durable responses or significant clinical efficacy in large phase III trials, presenting both opportunities and challenges for future development. Decades of research have greatly deepened our understanding of cancer vaccines, and the design of an optimal vaccine remains a delicate process. This process requires careful consideration of antigen selection, adjuvant incorporation, administration methods, combination with other therapies, and identification of the appropriate patient population.” (In particular, page 20, whole document). The specification is not enabled for the use of any kits for preventing cancer.
The specification fails to provide guidance as to how to prevent disease using any of the recited agents. The art is highly unpredictable as to what will be a therapy for any of the recited diseases, so it would require an undue amount of experimentation for one of ordinary skill in the art to practice the claimed invention commensurate in the scope with the claims. The invention may encompass pharmaceutical compositions which treat cancer, but the specification does not disclose how to totally prevent cancers generally using the claimed peptides and compositions thereof.
Since no in vivo studies were used as model system to prevent any disorder it is not clear that reliance on the in vitro data accurately reflects the relative animal efficacy of the claimed therapeutic strategy. The specification does not adequately teach how to effectively treat any disorders or reach any therapeutic endpoint in animals by administrating the peptides, much less any cancer encompassed by the instant claims. The specification does not teach how to extrapolate data obtained from the in vitro studies to the development of effective in vivo animal therapeutic treatment, commensurate in scope with the claimed invention. There must be a rigorous correlation of biological activity between the disclosed in vitro activity and an in vivo effectiveness to establish a method of preventing disease.
Although, the specification describes in vitro experiments, there is no correlation on this record between the in vitro studies and the preventing cancer in currently available form for humans or animals. It is not enough to rely on in vitro studies where, as here, a person having ordinary skill in the art has no basis for perceiving those studies as constituting recognized screening procedures with clear relevance to efficacy in humans or animals (emphasis added). Ex parte Maas, 9 USPQ2d 1746
In view of the absence of a specific and detailed description in Applicant's specification of how to effectively use the genus of compositions as claimed, absence of working examples providing evidence which is reasonably predictive that the genus of claimed kits are effective for in vivo use for prevention of disease, and the lack of predictability in the art at the time the invention was made, an undue amount of experimentation would be required to practice the claimed kits with a reasonable expectation of success.
Substantiating evidence may be in the form of animal tests, which constitute recognizedscreening procedures with clear relevance to efficacy in humans. See Ex parte Krepelka, 231USPQ 746 (Board of Patent Appeals and Interferences 1986) and cases cited therein. Ex parteMaas, 9 USPQ2d 1746.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
12. Claims 16, 21-24, 26-28 and 33-38 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is in possession of: the peptide consisting of SEQ ID NO:61 which inhibits tetramerization of the lactate dehydrogenase subunits; and the peptides of SEQ ID NOs 6-22, 30-35, 55-58, 61-65 and 67-68 without any specified function and compositions and kits thereof.
Applicant is not in possession of: a polypeptide that inhibits tetramerization of the lactate dehydrogenase subunits, said polypeptide comprising the amino acid sequence of SEQ ID NO:5-22, 30-35, 55-58, 62-65 and 67-68 and compositions and kits thereof.
The claims encompass polypeptides which do not inhibit tetramerization of the lactate dehydrogenase subunits. The skilled artisan cannot envision all the polypeptide possibilities recited in the instant claims.
The claimed linear sequences of SEQ ID NOs:6-20 encompasses an enormous number of polypeptides. In addition to each of the 8-19 amino acids in SEQ ID NOs:6-20, the peptides may comprise up to 11-22 additional amino acids added onto the N- and/or C-terminus of the peptide. Furthermore, SEQ ID Nos 18-20 comprise variable amino acids within the recited sequences. In the same way, cyclic peptides 67 and 68 comprise a variable amino acid each.
The art of Thabault et al. (PTO-892 mailed on 06/18/2025; Reference U) teaches many of the peptides encompassed by the claimed invention do not inhibit tetramerization of the lactate dehydrogenase subunits . The reference teaches that only one peptide, “macrocyclic peptide 7” of Table 3 (CTLKCKLI p-tetrafluorophenyl linker) was able to inhibit the tetramerization of the lactate dehydrogenase subunits. (In particular, Figure 9, whole document) There is no correlation between the structure of the peptides and the function of being able to inhibit the tetramerization of the lactate dehydrogenase subunits. As such, the specification has not adequately described the genus of polypeptides comprising SEQ ID NO:6-20, 30-35, 55-58, 61-65 and 67-68 which have the function of inhibit the tetramerization of the lactate dehydrogenase subunits.
One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
"Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features" Ex parte Kubin (83 U.S.P.Q.2d 1410 (BPAI 2007)), at page 16. In this instant case, Applicants have not provided the requisite identifying structural features of the antibodies encompassed. "Without a correlation between structure and function, the claim does little more than define the claimed invention by function" supra, at page 17.
While the instant specification does disclose certain peptides with the claimed functional attributes, the instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of peptides of SEQ ID NO:5 encompassing the functional / structural limitations encompassed in the claims.
In addition, the specification does not provide sufficient written description as to the correlation between the chemical structure and function. Applicant was not in possession of the claimed genus by providing sufficient structural and functional characteristics of the species or genus of such claimed peptides encompassed by the instant claim language, coupled with a known or disclosed correlation between function and structure. A skilled artisan cannot visualize or recognize the identity of the members of the genus that exhibit this functional property.
The Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
The specification fails to provide a description of the function-identifying structures required for the genus of peptides encompassing the functional limitations encompassed in the claims.
The patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014).
The specification at best describes a plan for making the genus of peptides encompassing the functional limitations encompassed in the claims encompassed by the claimed limitations, and then identifying those that satisfy claim limitations, but mere “wish or plan” for obtaining claimed invention is not sufficient.Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011).
In 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 court stated that in order to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, 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 at page 1358). The instant disclosure, including the claims fail to disclose a representative number of species falling with the scope of the genus or structural common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus. It is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361). 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).
“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 claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.” See Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005). “A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus.” See AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69.
A “representative number of species" means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
With respect to representative number of species, see AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014) Also, see MPEP 2163 II(A)(3)(a))(ii) 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. 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.").
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The “structural features common to the members of the genus” needed for one of skill in the art to 'visualize or recognize' the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural “stepping stone” to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
There is insufficient written description for genus of peptides of SEQ ID NO:5 encompassing the functional limitations encompassed in the claims at the time the invention was filed and as disclosed in the specification as filed under the written description provision of 35 USC 112.
Applicant’s arguments filed on 04/29/2026 have been fully considered, but are not found persuasive.
Applicant argues:
“The Office Action rejected claims 16, 21-24, and 26-38 under 35 U.S.C. § 112(a) for allegedly failing to comply with the written description requirement.
The Examiner overlooks the disclosure of the present application that several linear (Table 2) or cyclic (Table 3) polypeptides are capable of binding LDH subunits and/or inhibiting LDH subunits tetramerization.
In particular, the Examiner alleges that Thabault et al. ("Interrogating the Lactate Dehydrogenase Tetramerization Site Using (Stapled) Peptides." Journal of medicinal chemistry vol. 63,9 (2020): 4628-4643) discloses that only "macrocyclic peptide 7" of Table 3 (CTLKCKLI) was able to inhibit the tetramerization of the lactate dehydrogenase subunits.
This allegation seems to be an incorrect interpretation of the document. At best, Thabault et al. indicates that macrocyclic peptide 7 is the most potent one, but not that the other ones do not enable the claimed technical effect. For example, the last paragraph of the conclusion of the documents recites that "these short peptides and their stapled derivatives, especially macrocycle 7, represent a promising molecular framework for the further development of more potent LDH disruptors. They constitute, together with the dimeric forms of LDH, valuable pharmacological tools for the identification of new molecules interacting with LDH tetramerization sites."
It is noted that none of the sequences listed in claim 16 correspond to the epitopes envisaged by Thabault et al.
The Inventors have shown that the claimed linear and cyclic peptides demonstrate positive binding at the tetramerization site, at least based on NMR WATERLOGSY epitope mapping, and, for a further selection, also using an MST experiment.
Further, the Inventors have shown that the affinity toward the target is not the only parameter to be considered for predicting efficient inhibition of tetramerization.
Such results are provided on pages 47-55 of the application as filed, thus enabling the general concept of LDH tetramerization inhibition through the binding of N-terminal isolated fragments, along with an experimental framework including:
For Table 2 and pages 47-47, a selection of linear polypeptides among those demonstrating positive binding with NMR WATERLOGSY screening;
For Table 3 and page 49, a demonstration of the feasibility of cyclic inhibitory peptides, based on the structural study of SEQ ID NO: 31;
For Table 4, and pages 54-55, structural basis for an extrapolation toward macrocyclic peptides.
Indeed, experimental data is shown in the application as filed, in the context of the SEQ ID NO: 31, that the N-terminal region of the LDH peptide is endowed with inhibitory properties, also as a cyclic peptide.
Although the SEQ ID NO: 31 cannot compete with the LDHB native arm (see page 49, lines 19-20), and is thus not able to disrupt an already formed LDHB tetramer, it is surprisingly shown to interfere LDHB in a pre-dissociation dependent manner (see page 50, lines 15-19).
Hence, it was surprisingly found by the applicant that the polypeptides of the invention act as inhibitors of LDH tetramerization (Examples 1 and 2), and that these inhibitors are capable of exerting anticancer effects on Mia Paca-2 human pancreatic cancer cells (Example 3).
Accordingly, Applicant respectfully requests withdrawal of these rejections.”
It is the Examiner’s position for all of the reasons cited supra that the rejection stands for reasons of record.
Applicant’s argument that “It is noted that none of the sequences listed in claim 16 correspond to the epitopes envisaged by Thabault et al.” is unpersuasive. The art of Thabault et al. (PTO-892 mailed on 06/18/2025; Reference U) is Applicant’s own work and it teaches many of the peptides encompassed by the claimed invention do not inhibit tetramerization of the lactate dehydrogenase subunits . The reference teaches that only one peptide, “macrocyclic peptide 7” of Table 3 (CTLKCKLI p-tetrafluorophenyl linker) was able to inhibit the tetramerization of the lactate dehydrogenase subunits. (In particular, Figure 9, whole document).
The specification on pages 16-17 teaches
“In some embodiments, the cyclic polypeptide of the invention comprises, or consists in, an amino acid sequence represented by SEQ ID NO: 55 (MP1), i.e., an amino acid sequence represented by CTLKCKLI, wherein the cysteine residues are linked by m-benzyl. In some embodiments, the cyclic polypeptide of the invention comprises, or consists in, an amino acid sequence represented by SEQ ID NO: 61 (MP7), i.e., an amino acid sequence represented by CTLKCKLI, wherein the cysteine residues are linked by p-tetrafluorophenyl. In some embodiments, the cyclic polypeptide of the invention comprises, or consists in, an amino acid sequence represented by SEQ ID NO: 62 (MP8), i.e., an amino acid sequence represented by CTLKCKLI, wherein the cysteine residues are linked by o-benzyl. In some embodiments, the cyclic polypeptide of the invention comprises, or consists in, an amino acid sequence represented by SEQ ID NO: 63 (MP9), i.e., an amino acid sequence represented by CTLKCKLI, wherein the cysteine residues are linked by p-benzyl.”
Applicant’s argument that SEQ ID NO:31 was “surprisingly shown to interfere LDHB in a pre-dissociation dependent manner” and “Hence, it was surprisingly found by the applicant that the polypeptides of the invention act as inhibitors of LDH tetramerization (Examples 1 and 2), and that these inhibitors are capable of exerting anticancer effects on Mia Paca-2 human pancreatic cancer cells (Example 3)” is not persuasive. Adequate written description requires a lack of surprises. The specification must demonstrate a correlation between the structure of the molecules encompassed and the function recited.
There is no correlation between the structure of the peptides recited in claim 16 and the function of being able to inhibit the tetramerization of the lactate dehydrogenase subunits. Applicant has not pointed to data to show that the recited peptide have been shown to inhibit tetramerization of the lactate dehydrogenase subunits as claimed. Applicant’s argument that the peptides are “capable of binding LDH subunits and/or inhibiting LDH subunits tetramerization” is not persuasive. The claims do not recite this. The claims recite that the peptides are able to inhibit the tetramerization of the lactate dehydrogenase subunits. The art of Thabault et al. shows that these claimed peptides cannot perform this function. So, the sequences themselves in the claim are not adequately described, much less peptides which comprise additional amino acids added onto the recited peptides which cannot perform this function by themselves. It is noted that LB8 is SEQ ID NO:65, the peptides 1 and 7-9 in Table 3 are encompassed by SEQ ID NOs 31, 55 and 61-63; peptide 2 is encompassed by SEQ ID NOs 33 and 56; peptide 3 is encompassed by SEQ ID Nos 30 and 57; peptide 4 is encompassed by SEQ ID No:58; peptide 6 is encompassed by SEQ ID NO:34; peptide 10 is encompassed by SEQ ID NO:64; and peptides 11-12 are encompassed by SEQ ID NO:65. The reference teaches that the only one of these cyclic peptides that inhibit the tetramerization of the lactate dehydrogenase subunits is “macrocyclic peptide 7” of Table 3 (CTLKCKLI p-tetrafluorophenyl linker).
As such, the specification has not adequately described the genus of polypeptides comprising SEQ ID NO: 6-22, 30-35, 55-58, 61-65 and 67-68 which have the function of inhibiting the tetramerization of the lactate dehydrogenase subunits.
13. 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.
14. Claims 16, 23 and 26-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent Application Publication 2015/0079119 (PTO-892 mailed on 12/29/2025; Reference A) as evidenced by the attached sequence alignment.
U.S. Patent Application Publication 2015/0079119 teaches the sequence of reference SEQ ID NO:370 ‘MATLKEKLIAGSF’ (which is a 13 amino acid peptide comprising instant SEQ ID NOs:17-20) for use a peptide component of an anti-cancer vaccine (In particular, paragraph [252], Table 12, whole document).
The reference teaches the use of peptides in cancer vaccines further comprising pharmaceutically acceptable carriers and vehicles (In particular, paragraph [0188]-[0192], whole document) and kits thereof (In particular, paragraph [0198], whole document).
No more of the reference is required than that it sets forth the substance of the invention. The claimed functional limitations would be inherent properties of the referenced sequences. Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Since the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
The reference teachings anticipate the claimed invention.
15. No claim allowed.
16. It appears that the cyclic peptides consisting of an amino acid sequence selected from the group consisting of SEQ ID Nos 30-35, 55-58, 61-65 and 67-68 are free of the art.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
May 16, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
Prosecution Insights