DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Please note that the Patent Examiner of your application has changed. All communications should be directed to Mary Lyons, Art Unit 1645, whose telephone number is (571)272-2966.
Information Disclosure Statement
3. The listing of references in the specification is not a proper information disclosure statement (IDS) because 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office; and MPEP § 609.04(a) states "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the Examiner on form PTO-892, or by Applicant on an IDS, they have not been considered.
Claim Status
4. The amendment, filed 12/10/25, has been entered.
5. Claims 1-3, 5, 40-44, 70-75, and 98-102 are pending. Claims 4, 6-39, and 76-97 are cancelled. Claims 98-102 are newly added. Claims 1,3, 5, and 40-43 are amended. Claims 70-75 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/30/25. Claims 1-3, 5, 40-44, 70-75, and 98-102 are under examination.
Withdrawal of Objections/Rejections
6. The following are withdrawn from the Office Action, filed 06/26/25:
The objection to claim 40 under 37 CFR 1.75(c) as being in improper form, found on page 2 at paragraph 1, is withdrawn in light of Applicant’s amendments thereto. Claim 40 will now be treated on the merits.
The rejections of claims 3, 40, 41, and 42 found on pages 2-3 at paragraphs 2, 3, and 4, are each withdrawn in light of Applicant’s amendments thereto.
The rejection of claims 1-3, 5, and 40-44 under 35 U.S.C. 102(a)(1) as being anticipated by Fontana, found on page 4 at paragraph 5, is withdrawn in light of Applicant’s amendments thereto.
New Rejections Necessitated by Applicant’s Amendments
New Rejection: Claim Rejections – 35 USC § 112
7. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
8. Claim 40 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As amended, claim 40 now properly depends from claim 1 (see withdrawn objection above). Claim 1 recites “ A pharmaceutical composition comprising a polypeptide comprising a) an amino acid sequence consisting of residues 35-289 of SEQ ID NO: 8 …” and claim 40 recites “…wherein the polypeptide … is fused or conjugated to a polypeptide comprising at least 35 amino acid residues from any one of SEQ ID NOs:1-7 and 9-35, or an amino acid sequence which has at least 80% sequence identity with an amino acid sequence comprised of at least 35 amino acid residues of any one of SEQ ID NOs: 1-7 and 9-35”.
The transitional term "comprising", is inclusive or open-ended and does not exclude additional, unrecited elements or method steps; see, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). The transitional phrase "consisting of" excludes any element, step, or ingredient not specified in the claim; see, e.g., In re Gray, 53 F.2d 520, 11 USPQ 255 (CCPA 1931); Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948). However, when the phrase "consists of" appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole (MPEP 2111.03).
Therefore, “…an amino acid sequence consisting of residues 35-289 of SEQ ID NO: 8” (see claim 1) cannot be subsequently fused or conjugated to any more amino acids (i.e. another polypeptide; see claim 40) because a claim which depends from a claim which "consists of" the recited elements or steps cannot add an element or step; MPEP 2113.01.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
New Rejection: Claim Rejections - 35 USC § 112
9. 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.
10. Claims 1-3, 5, 40-44, 70-75, and 98-102 are rejected under 35 U.S.C. 112(a) 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, at the time the application was filed, had possession of the claimed invention.
Instant claims are drawn to pharmaceutical composition(s) comprising a polypeptide comprising a) an amino acid sequence consisting of residues 35-289 of SEQ ID NO: 8, or b) an amino acid sequence consisting of at least or exactly 35 contiguous amino acid residues from the amino acid sequence of a (i.e. fragments thereof), or c) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of a) or b (i.e. variants thereof) said polypeptide being antigenic in a mammal; and an immunological adjuvant and a pharmaceutically acceptable carrier, vehicle or diluent.
Consequently, it is the Office’s position that (1) the claim(s) constitute(s) a "broad generic claim” based on the lack of guidance regarding “fragments” (i.e. sequences only having as little as 35 consecutive amino acids) and/or “variants” (i.e. which 40% of the amino acids may be substituted within the claimed sequence, i.e. residues 35-289 of SEQ ID NO: 8, and/or i.e. within a fragment thereof); and (2) the claimed genus has substantial variation because of the numerous permutations permitted.
However, the specification does not provide adequate written description to identify the broad genus of the claims because, inter alia, the specification does not disclose a correlation between the necessary structure of the polypeptide (e.g. which amino acids must be maintained and which may be substituted in a variant and/or eliminated in a fragment) and the claimed function to be maintained (e.g. antigenic in a mammal). It is noted that while the description of the ability of a claimed polypeptide sequence may generically describe that polypeptide molecule's function, it does not describe the polypeptide itself. For example, the specification fails to identify critical amino acids or subsequences within residues 35-289 of SEQ ID NO: 8 that must be retained in order to maintain the claimed antigenicity (i.e. functional activity). Consequently, the specification fails to describe the common attributes or structural characteristics that identify the members of this genus and because the genus of sequences is highly variable (i.e. each sequence has a unique structure; see MPEP 2434), the characteristics of “antigenic in a mammal”, is insufficient to describe the genus. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing a massive number of partial structures claimed only by a functional characteristic (i.e. polypeptide fragments, variants, variants of fragments, and/or fragments of variants) because, without an art-recognized structure-function correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. Thus, disclosure of function alone is little more than a wish for possession and it does not satisfy the written description requirement; See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
Further, MPEP §2163 states that if a biomolecule is described only by a functional characteristic (as in the instant case), without any disclosed correlation between function and structure of the sequence (as in the instant case), it is not sufficient for written description purposes, even when accompanied by a method of obtaining the claimed sequences. MPEP §2163 does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Although the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number to adequately describe a broad genus. For example, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus (e.g. see In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618). Furthermore, the disclosure of only one or two 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 re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In the instant case, the specification provides complete structural information for SEQ ID NO: 8, including a fragment of SEQ ID NO: 8 consisting of residues 35-289 (i.e. 255 residues as found in newly amended claim 1; see the Table on page 75 combined with the Group 12 entry in a Table on page 88) which was antigenic in mice (see Results in Table on page 97). However, the claims, as written, also encompass partial structures of that 255-residue fragment of SEQ ID NO: 8 (e.g. additional fragments as small as 35 residues but, up to and including, as many as 220 residues, and/or 60-99% variants of any of those fragments, and/or 60-99% variants of the 255 residues, and/or fragments as small as 35 residues but, up to and including, as many as 220 residues of those variants). Yet, the specification does not adequately describe any of these polypeptide fragments, variants, variants of fragments, and/or fragments of variants that maintain the claimed functional properties of antigenicity in mammals. Accordingly, the specification also does not provide adequate written description to identify the broad and variable genus of the claims because, inter alia, it does not describe a sufficient number and/or a sufficient variety of representative species to reflect the variation within the genus (i.e. appears to be zero species sufficient described for the partial structures of fragments and/or variants with both the structural and functional features). Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous sequence fragments and variants having both the claimed structural attributes and functional properties have not yet been identified and MPEP 2163 which states an adequate written description of a chemical invention requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed; see, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004).
Accordingly, it is the Office' s position that the 60-99% variants and less than 255 amino acid fragments have not been described with sufficient particularity, such that one skilled in the art would recognize that Applicant had possession of the claimed invention, at the time of filing, because of (A) a lack of a correlation, known or disclosed, between the claimed functional requirements and the structures that meet those requirements; and/or (B) a lack of a representative number and variety of species to constitute possession of the full scope of the claimed genus.
With regards to the state of the art, at the time of filing, vaccine development for Neisseria gonorrhoeae was still under development and thus necessarily unpredictable, as evidenced by, for example, Jefferson et al. 2021 (Sexually Transmitted Neisseria gonorrhoeae Infections - Update on Drug Treatment and Vaccine Development; Medicines 8, 11: 1-22). Jefferson teaches gonorrhea, a sexually transmitted infectious disease caused by the bacterium Neisseria gonorrhoeae remains an intractable global health problem despite continuing efforts to curtail its health impacts (see introduction). Jefferson teaches the lack of natural immunity in both symptomatic and asymptomatic patients has impeded development of an effective anti-gonococcal vaccine and humoral immune responses to N. gonorrhoeae tend to be modest, with anti-body production in infected individuals characterized as only slightly increased compared to uninfected individuals and not protective against reinfection and that the potential role of antibodies in immunologic clearance of the pathogen from the host remains unclear (see introduction; Table 1 and section 3.3). Jefferson teaches there is no effective FDA-approved prophylactic against N. gonorrhoeae infections (see pages 8-9, bridging section). Thus, the state of the art supports that even the skilled artisan requires guidance on the critical structures of the antigenic polypeptide per se (e.g. its sequence and/or critical domains within its sequence) and therefore does not provide adequate written description support for which structural features of the polypeptide would predictably retain their functional activity (i.e. the state of the art is not sufficient to identify which amino acids must be conserved in order to maintain the claimed functions of antigenicity in mammals).
Consequently, neither the specification nor the state of the art provides sufficient written description to support the genus encompassed by the claims. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Given the above analysis of the factors as a whole, which the courts have determined are critical in determining whether Applicant is in possession of the claimed invention, Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
New Rejection: Claim Rejections - 35 USC § 112
11. Claims 1-3, 5, 40-44, 70-75, and 98-102 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for pharmaceutical compositions comprising a polypeptide having an amino acid sequence consisting of residues 35-289 of SEQ ID NO: 8; the specification does not reasonably provide enablement for immunogenic compositions comprising all of the fragments and variants thereof. 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.
Factors to be considered in determining whether undue experimentation is required, are set forth in In re Wands, 8 USPQ2d 1400. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and (8) the breadth of the claims. Although all the factors were considered, the most relevant ones are discussed below. In the instant case:
Nature of the invention: The nature of the invention is/are pharmaceutical composition(s) comprising a polypeptide comprising a) an amino acid sequence consisting of residues 35-289 of SEQ ID NO: 8, or b) an amino acid sequence consisting of at least or exactly 35 contiguous amino acid residues from the amino acid sequence of a (i.e. fragments thereof), or c) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of a) or b (i.e. variants thereof) said polypeptide being antigenic in a mammal; and an immunological adjuvant and a pharmaceutically acceptable carrier, vehicle or diluent. Therefore, the nature of the invention is a chemical case, where there is natural unpredictability in performance of certain species or sub-combinations other than those specifically enumerated; see MPEP 2163. Accordingly, it is the Office’s position that undue experimentation would be required to practice the full scope of the claimed invention, with a reasonable expectation of success, because it would not be predictable from the disclosure of one particular species (e.g. a fully described sequence) what other species (e.g. sequence fragments and variations thereof) may or may not work; see MPEP 2164.03.
Breadth of the claims: The broadest reasonable interpretation of the claims covers numerous partial structures (i.e. fragments of a 255-residue fragment of SEQ ID NO: 8, including those as small as 35 residues but, up to and including, as many as 220 residues, and/or 60-99% variants of any of those fragments, and/or 60-99% variants of the 255 residues, and/or fragments as small as 35 residues but, up to and including, as many as 220 residues of those variants) that maintain the claimed functional properties of antigenicity in mammals. However, without guidance on which of the structural components are required (i.e. which amino acids must be conserved) to maintain their claimed functions (i.e. antigenicity in mammals) undue experimentation would be required to determine which of the numerous structures actually work. Accordingly, undue experimentation would be required to practice the full scope of the claimed invention, with a reasonable expectation of success, because while enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, the specification must provide a reasonable amount of guidance with respect to the direction in which the experimentation should proceed and such guidance has not been provided in the instant specification (see below).
Amount of direction provided by Inventor and Existence of Working Examples: The specification provides complete structural information for SEQ ID NO: 8, including a fragment of SEQ ID NO: 8 consisting of residues 35-289 (i.e. 255 residues as found in newly amended claim 1; see the Table on page 75 combined with the Group 12 entry in a Table on page 88) which was antigenic in mice (see Results in Table on page 97). However, the claims, as written, also encompass partial structures of that 255-residue fragment of SEQ ID NO: 8 (e.g. additional fragments as small as 35 residues but, up to and including, as many as 220 residues, and/or 60-99% variants of any of those fragments, and/or 60-99% variants of the 255 residues, and/or fragments as small as 35 residues but, up to and including, as many as 220 residues of those variants). Yet, the specification does not sufficiently disclose any of these polypeptide fragments, variants, variants of fragments, and/or fragments of variants that maintain the claimed functional properties of antigenicity in mammals. Accordingly, the scope of the claims is extremely broad compared to the guidance and exemplification provided in the specification and the only way to determine if the functional property of a sequence variant or fragment is indeed retained, is empirical testing of each and every one encompassed. Consequently, based on the almost unfathomable number of possibilities, a non-routine amount of experimentation would be required to practice the full scope of the invention, with a reasonable expectation of success, because testing such a vast number of options would be easily recognized by the skilled practitioner to be disproportionately demanding and thus rise to the level of non-routine.
State of the Prior Art and Level of Predictability in the Art: With regards to the state of the art, at the time of filing, vaccine development for Neisseria gonorrhoeae was still under development and thus necessarily unpredictable, as evidenced by, for example, Jefferson et al. 2021 (Sexually Transmitted Neisseria gonorrhoeae Infections - Update on Drug Treatment and Vaccine Development; Medicines 8, 11: 1-22). Jefferson teaches gonorrhea, a sexually transmitted infectious disease caused by the bacterium Neisseria gonorrhoeae remains an intractable global health problem despite continuing efforts to curtail its health impacts (see introduction). Jefferson teaches the lack of natural immunity in both symptomatic and asymptomatic patients has impeded development of an effective anti-gonococcal vaccine and humoral immune responses to N. gonorrhoeae tend to be modest, with anti-body production in infected individuals characterized as only slightly increased compared to uninfected individuals and not protective against reinfection and that the potential role of antibodies in immunologic clearance of the pathogen from the host remains unclear (see introduction; Table 1 and section 3.3). Jefferson teaches there is no effective FDA-approved prophylactic against N. gonorrhoeae infections (see pages 8-9, bridging section). Thus, the state of the art supports that even the skilled artisan requires guidance on the critical structures of the antigenic polypeptide per se (e.g. its sequence and/or critical domains within its sequence) and therefore does not provide enablement for which structural features of the polypeptide would predictably retain their functional activity (i.e. the state of the art is not sufficient to identify which amino acids must be conserved in order to maintain the claimed functions of antigenicity in mammals). Accordingly, because the claimed functions cannot be predicted from the claimed partial structures or variations thereof, the functional characteristics must be determined empirically (i.e. after the fact). Consequently, the full scope of the claims is not enabled because even the skilled artisan cannot make and use the invention, with a reasonable expectation of success, without an undue amount of experimentation, based on the astronomically vast number of sequence variations and fragments permitted.
Relative Skill of Those in the Art: The relative level of skill of those in the art is deemed to be high (e.g. PhD level); however, even one of skill in the art could not predictably extrapolate the teachings in the specification, limited to a 255-residue fragment of SEQ ID NO: 8 with antigenicity in mice, to all the partial structures (i.e. fragments of, including those as small as 35 residues but, up to and including, as many as 220 residues, and/or 60-99% variants of any of those fragments, and/or 60-99% variants of the 255 residues, and/or fragments as small as 35 residues but, up to and including, as many as 220 residues of those variants) required to maintain the same antigenicity in all mammals, including humans. The skilled artisan simply cannot envision the structures required, thus conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method used to determine such structures or to test for such properties, after the fact. Thus, even one of skill in the art, would have to engage in undue experimentation to determine which variations and which fragments retain the necessary functional properties and thereby carry out the full scope of the invention as claimed.
Quantity of Experimentation Necessary Based on Content of the Disclosure: The specification does not enable the genus because where the results are unpredictable, the disclosure of a single species (i.e. a single, well-defined sequence with antigenic properties) usually does not provide an adequate basis to support generic claims. This is because it is not obvious from the disclosure of one particular species, what other species will work; see MPEP 2164.03. One of skill in the art would neither expect nor predict the appropriate functioning of the numerous fragments and variants, and accordingly, without such guidance, the experimentation left to those skilled in the art is unnecessarily and improperly extensive and undue. It is noted that providing methods for determining the claimed functional properties, would not reduce the amount of experimentation required because the functional properties still must be determined empirically (i.e. after the fact). Therefore, the scope of enablement provided to one skilled in the art is not commensurate with the scope of protection sought by the claims.
Therefore, in view of the lack of guidance and direction provided by Applicant there would be undue experimentation required to practice the claimed partial structures (e.g. sequence fragments and sequence variations), with a reasonable expectation of success, absent a specific and detailed description in Applicant's specification of how to effectively make and/or use the full scope of the claimed invention. Thus, Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
Conclusion
12. No claims are allowed.
13. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
14. 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.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY MAILLE LYONS whose telephone number is (571)272-2966. The examiner can normally be reached on Monday-Friday 8 am to 5 pm EST. 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. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker can be reached on (571)-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY MAILLE LYONS/Examiner, Art Unit 1645
March 23, 2026