DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ Amendment
1) Applicants’ amendment filed 07/21/26 in response to the non-final Office Action mailed 03/09/26 is acknowledged.
Status of Claims
2) Claims 1 and 20 have been amended via the amendment filed 07/21/2026.
Claims 11-22 are pending.
Claims 11-15, 17 and 19-22 are under examination.
Replacement Drawings
3) Applicants’ replacement drawings filed 07/21/26 are acknowledged.
Priority Application
4) Applicants’ filing on 07/21/26 of a copy of the certified English translation of the Brazilian priority application 102021010 filed 05/28/2021 is acknowledged.
Prior Citation of Title 35 Sections
5) The text of those sections of Title 35 U.S. Code not included in this action can be found in a prior Office Action References.
Prior Citation of References
6) The references cited or used as prior art in support of one or more rejections in the instant Office Action and not included on an attached form PTO-892 or form PTO-1449 have been previously cited and made of record.
Objection(s) to Specification & Claim(s)
7) 35 U.S.C § 132 states that no amendment shall introduce new matter into the disclosure of the invention. 37 CFR 1.75(d)(1) provides, in part, that ‘the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description.’
Claim 20, as amended, includes the newly added limitations “to a subject in need thereof”. Claim 11, as amended, includes the new limitation “a full length of” SEQ ID NO: 1 and the limitation a “full-length” peptide sequence of SEQ ID NO: 1. However, there is no antecedent basis and descriptive support in the as-filed specification for the above-identified limitations.
Rejection(s) Withdrawn
8) The rejection of claims 20-22 and 11-15 set forth in paragraph 10 of the Office Action mailed 03/09/26 under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, with regard to the written description issue is withdrawn in light of Applicants’ claim amendments. A new rejection is set forth in this Office Action to address the claims as amended. Given the art-recognized functional unpredictability, the broad scope of the genus and the issue of the lack of structure-function correlation remain.
9) The rejection of claim 20 set forth in paragraph 12(a) of the Office Action mailed 03/09/26 under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite is withdrawn in light of Applicants’ claim amendment.
10) The rejection of claims 21-22 set forth in paragraph 12(b) of the Office Action mailed 03/09/26 under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite is withdrawn in light of Applicants’ amendments to claim 11.
11) The rejection of claims 11-15 and 20-22 set forth in paragraph 15 of the Office Action mailed 03/09/26 under 35 U.S.C § 102(a)(1) as being anticipated by Araujo et al. (Infect. Immun. 73: 6017-6025, 2005, of record) is withdrawn given the structure-related ambiguity and indefiniteness indicated below in this Office Action.
12) The rejection of claims 17 and 19 set forth in paragraph 17 of the Office Action mailed 03/09/26 under 35 U.S.C § 103 as being unpatentable over Araujo et al. (Infect. Immun. 73: 6017-6025, 2005, of record) as applied to claims 12 and 11 and further in view of Mehrizi et al. (Parasite Immunology 40: e12538, pages 1 of 16 to 16 of 16, 25 May 2018, of record) is withdrawn given the structure-related ambiguity and indefiniteness in the amended 11 as indicated below in this Office Action.
Rejection(s) under 35 U.S.C § 112(a) or (Pre-AIA ), First Paragraph
13) The following is a quotation 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 35 U.S.C § 112 (pre-AIA ), first paragraph:
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 the invention.
14) Claims 11 and 20 and the dependent claims 12-15, 17, 19, 21 and 22 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 claims contain 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 the (pre-AIA ), the Applicant. This is a new matter rejection.
Claim 20, as amended, includes the newly added limitations “to a subject in need thereof”. Claim 11, as amended, includes the newly added limitation “a full length of” SEQ ID NO: 1 and the limitation a “full-length” peptide sequence of SEQ ID NO: 1. However, there is no descriptive support for the above-identified limitations. Therefore, the above-identified limitations in the claim(s) and/or the current scope of the claim(s) constitute new matter. See M.P.E.P 608.04 to 608.04(c).
Applicants are invited to point to the descriptive support in specific pages and lines of the disclosure, as originally filed, for the limitation identified above, or alternatively, remove the new matter from the claim(s). Applicants should specifically point out the support for any amendments made to the disclosure. See MPEP 714.02 and 2163.06.
15) Claims 20-22, 11-15 and 17 are rejected under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, as containing 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 purpose of the written description requirement is “to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.” In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). The analysis of whether the as-filed specification complies with the written description requirements calls for the Office to compare the scope of the claims with the scope of the description to determine whether Applicant has demonstrated possession of the full scope of the claimed invention at the time of the invention. In the instant application, an analysis of the scope of the claims and of the variant peptide sequence genus encompassed therein indicates the following.
Claims 20 and 22 are drawn to a method of preventing or treating a Trypanosoma cruzi infection or Chagas disease comprising administering to a subject in need thereof the composition of the amended claim 12. Claim 12, as amended, is drawn to a composition comprising one or more adjuvants and the chimeric protein of claim 11, which as amended comprises a chimeric protein comprising a peptide sequence with at least 80% identity with ‘a full length of SEQ ID NO: 1’, or a full-length peptide sequence of SEQ ID NO: 1. The SEQ ID NO: 1 is 573 amino acids in length. However, what precise structure is encompassed in the limitation ‘a full length of SEQ ID NO: 1’ (see lines 2 and 3 of claim 11) and the limitation “a” full length of SEQ ID NO: 1 (see line 4 of claim 11) is not clear. Assuming that Applicant is referring to the sequence of SEQ ID NO: 1, a peptide sequence comprised within a chimeric protein that is at least 80% identity with SEQ ID NO: 1 is a peptide sequence that is up to 20% non-identical to SEQ ID NO: 1. The composition of claim 13 is required to be a ‘vaccine’ comprising the composition of claim 12. Per claim 21, the composition administered to a subject in need thereof in the claimed method of preventing or treating a Trypanosoma cruzi infection is a ‘vaccine’. Thus, a peptide sequence with at least 80% identity with SEQ ID NO: 1 represents a huge genus encompassing peptide sequence species up to 20% non-identical with SEQ ID NO: 1 and shorter peptide sequence species of unlimited length/size and variable structure from within SEQ ID NO: 1, wherein the chimeric protein comprising these structurally divergent species is required to have the anti-Trypanosoma cruzi vaccine functions and the Chagas disease-preventing and Chagas disease-treating prophylactic and therapeutic functions. However, at the time of the invention, Applicants were not in possession of the full breadth of the variable peptide sequence genus identified supra and the full scope of the claimed invention.
Whether or not one of skill in the art would recognize that Applicant was in possession of the claimed invention as a whole at the time of invention is to be determined upon considering the actual reduction to practice, sufficient relevant identifying characteristics, disclosure of drawings or structural chemical formulas, method of making the claimed invention, level of skill and knowledge in the art, and predictability in the art. Under the written description provision of the 35 U.S.C § 112 (a) or pre-AIA , first paragraph, the structure of a representative number and variety of the encompassed structurally highly variable peptide sequence species is required to be correlated with the above-identified requisite prophylactic and therapeutic vaccine functions. The written description requirement can be met by describing the claimed subject matter to a person skilled in the art using sufficiently detailed, relevant identifying characteristics such as functional characteristics and correlating those functional characteristics with a disclosed structure. See Enzo Biochem v. Gen-Probe, 323 F.3d 956, 964, 967, 968 (Fed. Cir. 2002). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention. See e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). In the instant application, the structure of a sufficient number and variety of species encompassed within the variable structurally divergent peptide sequence genus has not been correlated with the above-identified requisite anti-Trypanosoma cruzi vaccine functions and the Chagas disease-preventing and Chagas disease-treating prophylactic and therapeutic functions in a subject in need thereof. This is important because the precise structure of the peptide sequence species that are up to 20% non-identical to SEQ ID NO: 1 and that retain the required anti-T. cruzi vaccine function is not disclosed. While peptide sequence species that are up to 20% non-identical to SEQ ID NO: 1 comprising therein random amino acid modifications such as amino acid substitutions, additions, deletions, insertions and/or other modifications anywhere along their entire length may be expected by those of skill in the art to be immunogenic, there is no predictability that such structurally modified variant peptide sequences would retain their three dimensional conformational integrity and the critical Trypanosoma cruzi-immunospecificity of the native SEQ ID NO: 1 such that the peptide sequence variant species comprised in the claimed chimeric protein and a vaccine comprising said sequence species would retain the requisite vaccine (protective) functions and the requisite therapeutic and prophylactic effects against Trypanosoma cruzi infections and Chagas disease. This is important because ‘[f]or 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’ (at 1106). 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 each genus as in the instant case, one must describe a sufficient variety of species to reflect the variation within the genus along with a concrete structure-function correlation. The Court in Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) stated that “[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”). The written description inquiry is case-specific and context-specific. It “depend[s] on the nature of the claimed invention and the knowledge of one skilled in the art at the time an invention is made and a patent application is filed.” Ariad, 560 at 1372. A number of factors guide the inquiry, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, and the predictability of the aspect at issue.” Ariad, 560 at 1372 [Emphasis added]. MPEP 2163 states [Emphasis added]:
The description needed to satisfy the requirements of (pre-AIA ) 35 U.S.C § 112 “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084. Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art.
Evidence required to demonstrate possession of the invention is fact-specific and varies inversely with the maturity and predictability of the technology area. Inventions in “unpredictable” arts are subject to greater scrutiny under the written description requirement, and require a greater showing of possession than more predictable arts. The state of the art at the time of the invention documents unpredictability associated with amino acid modifications within a protein or polypeptide sequence. For example, Mikayama et al. Proc. NatI. Acad. Sci. USA, 90: 10056-10060, 1993 (of record) taught that the three-dimensional structure of molecules is important for their biological function and even a single amino acid difference may account for markedly different biological activities. Skolnick et al. Trends in Biotechnology, 18: 34-39, 2000 (of record) taught that the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based on sequence homology is inaccurate, in part because of the multifunctional nature of proteins. See abstract and ‘Sequence-based approaches to function prediction’ on page 34. Skolnick et al. further taught that even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to function of the structurally related protein. See in particular abstract and Box 2. With regard to the structure-function relationship of an encoded amino acid sequence in general, Rudinger J. In: Peptide Hormones. (Ed) JA Parsons, University Park Press, pages 1-7, 1976 (of record) taught that ‘the significance of particular amino acid sequences for different aspects of biological activity cannot be predicted a priori but must be determined from case to case by painstaking experimental study’. See page 6 of Rudinger J. Rudinger J. further taught that ‘it is impossible to attach a unique significance to any residue in a sequence’ and that a ‘given amino acid will not by any means have the same significance in different peptide sequences, or even in different positions of the same sequence. See page 3 of Rudinger J. Furthermore, the art recognizes that defining epitopes is not easy and there is a confusing divergence between the textbook definition of epitope and the definition that is in use in published descriptions of experimental investigations and that epitopes must be empirically determined. See Greenspan et al. Nature Biotechnology 17: 936-937, 1999. Even with regard to conservative amino acid substitutions within a protein, Lazar et al. Mol. Cellular Biol. 8: 1247-1252, 1988 (of record) demonstrated that a substitution of the Leucine residue with a conservative amino acid residue such as, Isoleucine or Histidine, in the transforming growth factor (TGF) alpha led to a mutant protein with dramatically altered biological activities. Lazar et al. expressly stated that they ‘did not expect that a mutation of Leu to Ile (which have similar sizes and polarities) would cause such a strong effect’. See paragraph bridging left and right columns on page 1251; and third full paragraph on page 1251. In the instant application, with up to 20% sequence non-identity permitted within the peptide sequence species that are comprised in the administered vaccine, there is no predictability that the administered peptide sequence variant species would retain the conformational integrity and the T. cruzi-immunospecificity such that the various variant species in the vaccine would retain the requisite vaccine (protective) functions and the requisite therapeutic and prophylactic effects against Trypanosoma cruzi infections and Chagas disease. Clearly, in the instant case, a skilled artisan cannot immediately envision or recognize at least a substantial number and variety of members of the variable genus of the administered peptide sequences. A convincing structure-function correlation for the entire variant genus and the full scope of the claims is lacking.
MPEP § 2163.02 states: ‘an objective standard for determining compliance with the written description requirement is, does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’. In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). The courts have decided that the purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the 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 Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Applicants should note that written description provision of 35 U.S.C § 112(a) or pre-AIA , first paragraph is severable from its enablement provision, and written description requires more than a mere statement that something is part of the invention and a reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. A mere idea or unsubstantiated function is insufficient for written description; characterization of a representative number of species within the huge variable genus as claimed, with their precise structure correlated with the requisite or intended functions is required. With regard to the written description of a genus, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that "merely recite a description of the problem to be solved while claiming all solutions to it and ...... cover any compound later actually invented and determined to fall within the claim's functional boundaries."). Abbvie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 U.S.P.Q.2d 1780, 1790, 2014 BL 183329, 12 (Fed. Cir. 2014). In the instant case, Applicants’ specification does not contain a written description sufficient to show that they had possession of the full breadth of the variant peptide sequence genus and the full scope of the claimed invention at the time the application was filed. The instant claims do not meet the written description provision of 35 U.S.C § 112(a) or pre-AIA , first paragraph.
Rejection(s) under 35 U.S.C § 112(b) or (Pre-AIA ) Second Paragraph
16) 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.
17) Claims 11-15, 17 and 19-22 are rejected under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite, for failing to particularly point out and distinctly claim the subject matter which inventor or a joint inventor, or for the pre-AIA the Applicants regard as the invention.
(a) Claim 11, as amended, is ambiguous and indefinite in the recitation “a full length of SEQ ID NO: 1” (see line 2) because it is unclear what precise structure is encompassed in “a” full length of SEQ ID NO: 1. One of ordinary skill in the art cannot understand in an unambiguous way the scope of the claim. Do Applicants mean to convey that the element recited in part (i) of the amended claim 11 is a peptide sequence with at least 80% sequence identity with –the amino acid sequence of SEQ ID NO: 1--?
(b) Claim 11, as amended, is further ambiguous and indefinite in the limitation “a full-length peptide sequence of SEQ ID NO: 1” (see line 4) because it is unclear what precise structure is encompassed. The SEQ ID NO: 1 is 573 amino acids in length. The structural boundaries of the “a full-length peptide sequence of SEQ ID NO: 1” are not clear. Do Applicants mean to convey that the element recited in part (ii) of the amended claim 11 is –the amino acid sequence of SEQ ID NO: 1--?
(c) Claims 12-15, 17 and 19-22, which depend directly or indirectly from claim 11, are also rejected as being indefinite due to the indefiniteness identified supra in claim 11.
Conclusion
18) No claims are allowed.
19) Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. THIS ACTION IS MADE FINAL. Applicants are reminded of the extension of time policy as set forth in 37 C.F.R 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 extension fee pursuant to 37 C.F.R 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.
Correspondence
20) Any inquiry concerning this communication or earlier communications from the Examiner should be directed to S. Devi, Ph.D., whose telephone number is (571) 272-0854. A message may be left on the Examiner’s voice mail system. The Examiner is on a flexible work schedule, however she can normally be reached Monday to Friday from 7.00 a.m. to 4.00 p.m. (EST). If attempts to reach the Examiner by telephone are unsuccessful, the Supervisor of AU 1645, Jeffrey Stucker, can be reached at (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned (571) 273-8300.
21) Information regarding the status of an application may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center or Private PAIR to authorized users only. Should you have questions about access to Patent Center or the Private PAIR system, 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) at http://www.uspto.gov/interviewpractice.
/S. DEVI/
S. Devi, Ph.D.Primary Examiner
Art Unit 1645
September, 2026
