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 .
Information Disclosure Statement
2. The information disclosure statements (IDS) submitted on 01/10/24; 03/12/24; and 12/27/24 were filed and entered. The submissions are in compliance with the provisions of 37 CFR 1.97 and have been considered by the Examiner.
Election/Restrictions
3. Applicant’s election without traverse of Group I, in the reply filed on 01/27/26, is acknowledged. Applicant’s election of SEQ ID NO: 7, 8, 11 and 12, in the reply filed on 01/27/26, is also acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). However, upon further consideration, the sequence election is withdrawn.
Claim Status
4. Claims 23-60 are pending. Claims 41-60 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 01/27/26. Claims 23-40 are under examination.
Claim Objections
5. Claim 28 is objected to because of the following informalities: improper formatting. MPEP 608.01(m) states that “Each claim begins with a capital letter and ends with a period”. However instant claim 28 has periods after (2)(c) before “(a) An antibody…” and before “(b) An antibody…” and before “(c) An antibody…” Each of these periods must be removed and only the period at the completion of the claim should remain. Appropriate correction is required.
6. Claims 23, 28, 29, 30, 31 and 32 are each objected to because of the following informalities: improper recitation of species names. Latin names of microorganisms are properly recited with the genus name (i.e. first part of binomial identifier) capitalized and species name (i.e. second part of binomial identifier) in lower case, with both in italics, and having the genus name spelled out upon first usage, in order to be understood without requiring reference to the specification (i.e. see MPEP 2173.05(s); claims are to be complete in themselves). Thus, Neisseria gonorrhoeae should be Neisseria gonorrhoeae; Neisseria meningitidis should be written Neisseria meningitidis; and each genus listed in claims 31 and 32 should be written as Mycoplasma, Escherichia, Chlamydia, Pseudomonas, Staphylococcus, Legionella, and Streptococcus. Appropriate correction is required.
Claim Rejections – 35 USC § 112
7. Claims 23-40 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The term “derived” in each of claims 23, 28, 29, 30, and 33-36, is a relative term which renders the claim indefinite. The term “derivative” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In other words, to what degree of derivatization for the antigen and/or sample source is included vs. excluded in the claim scope?
Similarly, the term “derivative” in claim 23 (see line 12), is a relative term which renders the claim indefinite. The term “derivative” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In other words, to what degree of derivatization of an antibody is included vs. excluded in the claim scope?
Claims 33-36 are also indefinite because it is unclear if the sample per se is an actually component to be included in the kit or if the kit is merely for use with a particular type of sample. Thus, clarification is required.
Dependent claims do not clarify the issues identified above, thus, clarification is required to remove scope ambiguity and ascertain the metes and bounds of the claims.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 23-40 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. This is a written description rejection.
Instant claims are drawn to kits for detecting Neisseria gonorrhoeae in a sample, comprising a capture antibody for capturing a Neisseria gonorrhoeae-derived antigen in the sample; and a detection antibody having a detection label for labeling the Neisseria gonorrhoeae-derived antigen in the sample, wherein Neisseria gonorrhoeae is detected via an immune reaction between the Neisseria gonorrhoeae-derived antigen in the sample, the capture antibody, and the detection antibody to form a structure sandwiching the Neisseria gonorrhoeae-derived antigen, wherein the Neisseria gonorrhoeae-derived antigen is a ribosomal protein L7/L12 of Neisseria gonorrhoeae, wherein one of the capture antibody and the detection antibody is a first monoclonal antibody or its fragment or a derivative thereof, which causes an antigen-antibody reaction with an epitope containing one or more amino acid residues selected from the 2nd to 14th amino acid residues from the N terminal of the amino acid sequence of Neisseria gonorrhoeae L7/L12 shown in SEQ ID NO:1, wherein the other of the capture antibody and the detection antibody is a second monoclonal antibody or its fragment or a derivative thereof, which causes an antigen-antibody reaction with an epitope containing one or more amino acid residues selected from the 102nd to 123rd amino acid residues from the N-terminal of the amino acid sequence of Neisseria gonorrhoeae L7/L12 shown in SEQ ID NO:1 (see independent claim 23); and wherein as the amino acid sequence of a heavy chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:7, and, as the amino acid sequence of a light chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:8 (see dependent claim 24 and independent claim 28); and wherein the first monoclonal antibody comprises: as the amino acid sequence of a heavy chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:9, and as the amino acid sequence of a light chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:10; or as the amino acid sequence of a heavy chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:11, and as the amino acid sequence of a light chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:12 (see dependent claim 25 and independent claim 28).
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. which pieces of the antibody sequences may be removed and which must be retained); and “derivatives” (i.e. how much derivatization is permitted); and/or “variants” (i.e. which 20% of amino acids may be substituted within a claimed sequence) all the while retaining the claimed functions; and (2) the claimed genus has substantial variation because of the numerous options and combinations permitted. Thus, it is the Office's position that the antibody fragments, derivatives and 80% sequence variants 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.
For example, 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 antibody (e.g. which amino acids must be maintained as compared to which may be substituted in a variant or derivative and/or eliminated in a fragment) and the claimed function to be maintained (e.g. cause an antigen-antibody reaction with an epitope containing one or more amino acid residues selected from the 2nd to 14th amino acid residues from the N-terminal of the amino acid sequence of Neisseria gonorrhoeae L7/L12 shown in SEQ ID NO:1; and/or cause an antigen-antibody reaction with an epitope containing one or more amino acid residues selected from the 102nd to 123rd amino acid residues from the N-terminal of the amino acid sequence of Neisseria gonorrhoeae L7/L12 shown in SEQ ID NO:1; and/or having an efficiency in detecting the Neisseria gonorrhoeae-derived antigen more than 10 times higher than the efficiency in detecting a Neisseria meningitidis -derived antigen; see dependent claims 29 and 30; and/or not causing a cross-reaction with bacteria of the genera Mycoplasma, Escherichia, Chlamydia, Pseudomonas, Staphylococcus, Legionella, and Streptococcus in a sample; see dependent claims 31 and 32). It is noted that while the description of the ability of a claimed protein (antibody) sequence may generically describe that protein molecule's function, it does not describe the molecule itself. For example, the specification fails to identify critical amino acids or subsequences within SEQ ID NO: 7-12 that must be retained in an antibody fragment, derivative and/or 80% variant in order to maintain the claimed functional activities. Although the term “antibody” does impart some structure, the structure that is common to antibodies is generally unrelated to its antigen-binding function; therefore, correlation is less likely for antibodies than for other molecules. 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 the ability to function as an antibody with the ability to react to as little as one amino acid within a particular stretch of amino acids; and/or the capacity to detect Neisseria gonorrhoeae-derived antigen more than 10 times higher than the efficiency in detecting a Neisseria meningitidis-derived antigen; and/or the ability to not cause a cross-reaction with bacteria of the genera Mycoplasma, Escherichia, Chlamydia, Pseudomonas, Staphylococcus, Legionella, and Streptococcus in the sample, 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. antibody fragments, derivatives, and/or 80% sequence 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 appears to provide complete structural information for six antibodies classified into four groups (identified as species A, B, C, and D) comprising SEQ ID NO: 7-12 (see Example 1; Tables 1 and 2) but with varying functional properties including Antibody species A (NG1) which reacts with a partial sequence consisting of the 102nd to 123rd amino acid residues from the N-terminal, including the 115th amino acid from the N-terminal of Neisseria gonorrhoeae L7/L12; whereas Antibody species B (NG2, NG3) which reacts with a partial sequence consisting of the 2nd to 14th amino acid residues from the N-terminal of Neisseria gonorrhoeae L7/L12; and Antibody species C (NG4, NG5) which reacts with a partial sequence consisting of the 15th to 63rd amino acid residues from the N-terminal of Neisseria gonorrhoeae L7/L12; and Antibody species D (NG6) that reacts with a partial sequence consisting of the 64th to 101st amino acid residues from the N-terminal of Neisseria gonorrhoeae L7/L12; thereby providing two examples of an antibody that reacts with amino acid residues from the 2nd to 14th from the N-terminal of SEQ ID NO:1 (see Species B); and one example of an antibody that reacts with amino acid residues 102nd to 123rd from the N-terminal of SEQ ID NO: 1 (see Species A). However, the claims, as written, also encompass partial structures of antibodies comprising SEQ ID NOs 7-12 that are not adequately described. For example, there are no adequately described antibodies that bind to as little as one amino acid in SEQ ID NO:1, with the notable exception of Species A (i.e. disclosed as reactive with 115th residue). There are no antibody fragments or derivatives of antibodies adequately described that meet both structural and functionals requirements. There are no sequence variants having as little as 80% homology to SEQ ID NOs: 7, 8, 9, 10, 11 and/or 12 and the claimed functional properties listed above. Further, with regards to combinations of antibodies in the claims, the specification discloses results which show that only antibody combinations containing an Antibody Species A (labeled: NG1) had a clear difference in signal between the extracted sample solution containing Neisseria gonorrhoeae and the extracted sample solution containing Neisseria meningitidis (i.e. were actually able to detect Neisseria gonorrhoeae without cross-reacting); and therefore the specification describes that Antibody Species A is essential to generating an antigen-antibody reaction for the detection of Neisseria gonorrhoeae (see Example 2; Table 3 and [0114]). However, the independent claims, as written do not even require Antibody A per se. The specification discloses that only the combination of an Antibody Species A (i.e. NG1) with Antibody Species B (i.e. NG3) was able to detect Neisseria gonorrhoeae at concentrations as low as 1 to 2e4 cfu/mL and that, in contrast, the combination of Antibody Species A with Antibody species C or D could not detect Neisseria gonorrhoeae at the same concentrations (e.g. see Example 2; Table 4 and [0122]). Similarly, the specification describes that the combination of Antibody Species A with Antibody Species B showed good detection performance by ELISA, and was able to detect Neisseria gonorrhoeae at concentrations as low as 1 to 2e4 cfu/mL but that, in contrast, the combination of Antibody Species A with Antibody Species C failed to do so (e.g. see Example 4 and Table 5).
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 one species of the combined NG1 with either NG2 or NG3 sufficiently described). Further, the specification provides evidence that there is unpredictability in the results obtained from species other than those specifically enumerated (i.e. not all of the fully described antibodies and/or combinations of antibodies worked as claimed), and accordingly, the specification provides evidence that indicates ordinary artisans could not reliably predict the operability in the invention of any species other than the one disclosed (i.e. the combination of Antibody A: NG1 with either of Antibody B: NG2 or NG3).
Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous antibody fragments, derivatives, and 80% sequence variants having both the claimed structural attributes and claimed functional properties, used alone or in combination, have not yet been identified. Further, 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 one of skill in the art would not accept the disclosure of a kit comprising a combination of Antibody A, comprising SEQ ID NO: 7 & 8, with Antibody B, comprising either SEQ ID NOs 9 & 10 or 11 & 12, as either a sufficient number and/or variety of “representative species” for all of the antibody fragments, derivatives and 80% sequence variants, alone or in combination, encompassed by the broad and variable generic claims. Therefore, it is the Office’s position that one of skill in the art would not conclude that Applicant was in possession of the entire genus as claimed.
With regards to the state of the art, detection of Neisseria gonorrhoeae was under development, and thus necessarily unpredictable, as evidenced by, for example, Verma et al. 2016 (Gonorrhoea diagnostics: An update; Indian Journal of Medical Microbiology 34(2):139-145) teaches diagnosis of gonorrhea is an ongoing challenge because inter alia the organism is fastidious and requires meticulous collection and transport and that there remains a need for the detection via culture and non-culture methods and Mahapure et al. 2023 (A Review of Recent Advances in Our Understanding of Neisseria gonorrhoeae; Cureus 15(8):e43464. DOI 10.7759/cureus.43464) which teaches Point of Care diagnostic tests (POCTs) for gonorrhoeae remains a significant goal (i.e. under development) to provide precise and rapid detection of infections.
Furthermore, the art recognizes that the functional characteristics of an antibody are determined by its complete structure, as evidenced by, for example, Sela-Culang et al. 2013 (The structural basis of antibody-antigen recognition; Frontiers in Immunology 4(302):1-13) which teaches the hypervariable loops within the variable domains of antibody polypeptides are widely assumed to be responsible for antigen recognition while the constant domains are believed to mediate effector activation, but that recent analysis indicates that their clear functional separation between the two regions is an over-simplification (see abstract). Sela-Culang teaches some residues within the CDRs may not participate in antigen binding and some residues outside the CDRs (e.g. in framework regions and in the constant domains) often contribute critically to the integration with the antigen (see abstract). Sela-Culang teaches understanding the role of each structural element is essential for successful engineering of binding polypeptides (e.g. page 2, left column). Sela-Culang teaches almost all of the residues predicted to be part of an epitope may be considered as correct predictors as they will bind to some antibodies but also are false predictors as they don' t bind to the others and accordingly that predicting that a residue is not in an epitope may be either a true negative or a false negative depending on the anybody considered (page 2, right column). Sela-Culang teaches each CDR has its own unique amino-acid composition different from the composition of the other CDRs and that each CDR has a unique set of contact preferences favoring certain amino acids over others (page 5-6, bridging). Sela-Culang et al. teach the combined action of all six CDRs is the evolutionary response of the immune system that enables the antibody polypeptide to recognize virtually any surface patch on the antigen (page 6). Thus, the state of the art supports that the skilled artisan requires guidance on the critical structures of the antibody per se and thereby does not provide adequate written description support for which structural features of the sequences (i.e. which antibody fragments, derivatives and/or 80% sequence variants) would predictably retain their functional activity.
In addition, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) recently decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself; see Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
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 or the specification supports the claimed invention, Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 112
10. Claims 23-40 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for kits for detecting Neisseria gonorrhoeae having an antibody comprising SEQ ID NOs: 7 & 8 combined with an antibody comprising SEQ ID NOs 9 & 10 and/or 11 & 12; the specification does not reasonably provide enablement for kits for detecting Neisseria gonorrhoeae comprising otherwise mixed-and-matched antibody fragments, derivatives and/or 80% sequence 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 encompasses kits for detecting Neisseria gonorrhoeae in a sample, comprising a capture antibody and a detection antibody for capturing a Neisseria gonorrhoeae-derived antigen in the sample, wherein the Neisseria gonorrhoeae-derived antigen is a ribosomal protein L7/L12 of Neisseria gonorrhoeae, wherein one of the capture antibody and the detection antibody is a first monoclonal antibody or its fragment or a derivative thereof, which causes an antigen-antibody reaction with an epitope containing one or more amino acid residues selected from the 2nd to 14th amino acid residues from the N terminal of the amino acid sequence of Neisseria gonorrhoeae L7/L12 shown in SEQ ID NO:1 (i.e. instant SEQ ID NOs 9-12), wherein the other of the capture antibody and the detection antibody is a second monoclonal antibody or its fragment or a derivative thereof, which causes an antigen-antibody reaction with an epitope containing one or more amino acid residues selected from the 102nd to 123rd amino acid residues from the N-terminal of the amino acid sequence of Neisseria gonorrhoeae L7/L12 shown in SEQ ID NO:1 (i.e. instant SEQ ID NOs: 7 and 8; see independent claim 23); wherein the amino acid sequence of a heavy chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:7, and, as the amino acid sequence of a light chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:8 (see dependent claim 24 and independent claim 28); and wherein the first monoclonal antibody comprises: as the amino acid sequence of a heavy chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:9, and as the amino acid sequence of a light chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:10; or as the amino acid sequence of a heavy chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:11, and as the amino acid sequence of a light chain variable region, an amino acid sequence having a homology of 80% or more to the amino acid sequence of SEQ ID NO:12 (see dependent claim 25 and independent claim 28).
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. the combination of one fully described antibody with either of two other fully described antibodies) what other species (e.g. mixed and matched antibody fragments, derivatives and/or 80% sequence variants thereof) may or may not work; see MPEP 2164.03.
Breadth of the claims: The broadest reasonable interpretation of the claims covers an almost unfathomable number and diversity of partial structures including antibody fragments, derivatives and 80% sequence variations claimed only by functional properties and then mixed-and-matched in haphazard combinations. However, without guidance on which of the structural components are required (i.e. which amino acids must be maintained and/or conserved) to maintain their claimed functions (i.e. cause an antigen-antibody reaction with an epitope containing one or more amino acid residues selected from the 2nd to 14th amino acid residues from the N-terminal of the amino acid sequence of Neisseria gonorrhoeae L7/L12 shown in SEQ ID NO:1; and/or cause an antigen-antibody reaction with an epitope containing one or more amino acid residues selected from the 102nd to 123rd amino acid residues from the N-terminal of the amino acid sequence of Neisseria gonorrhoeae L7/L12 shown in SEQ ID NO:1; and/or detect a Neisseria gonorrhoeae-derived antigen more than 10 times higher than the efficiency in detecting a Neisseria meningitidis-derived antigen; and/or not cause a cross-reaction with bacteria of the genera Mycoplasma, Escherichia, Chlamydia, Pseudomonas, Staphylococcus, Legionella, and Streptococcus in the sample), undue experimentation would be require to determine which of the numerous structures, in which combinations, 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 appears to provide complete structural information for six antibodies classified into four groups (identified as species A, B, C, and D) comprising SEQ ID NO: 7-12 (see Example 1; Tables 1 and 2) but with varying functional properties including Antibody species A (NG1) which reacts with a partial sequence consisting of the 102nd to 123rd amino acid residues from the N-terminal, including the 115th amino acid from the N-terminal of Neisseria gonorrhoeae L7/L12; whereas Antibody species B (NG2, NG3) which reacts with a partial sequence consisting of the 2nd to 14th amino acid residues from the N-terminal of Neisseria gonorrhoeae L7/L12; and Antibody species C (NG4, NG5) which reacts with a partial sequence consisting of the 15th to 63rd amino acid residues from the N-terminal of Neisseria gonorrhoeae L7/L12; and Antibody species D (NG6) that reacts with a partial sequence consisting of the 64th to 101st amino acid residues from the N-terminal of Neisseria gonorrhoeae L7/L12; thereby providing two examples of an antibody that reacts with amino acid residues from the 2nd to 14th from the N-terminal of SEQ ID NO:1 (see Species B); and one example of an antibody that reacts with amino acid residues 102nd to 123rd from the N-terminal of SEQ ID NO: 1 (see Species A). However, the claims, as written, also encompass partial structures of antibodies comprising SEQ ID NOs 7-12 that are not sufficiently disclosed. For example, there are no sufficiently disclosed antibodies that bind to as little as one amino acid in SEQ ID NO:1, with the notable exception of Species A (i.e. disclosed as reactive with 115th residue). There are no antibody fragments, or derivatives of antibodies, sufficiently disclosed that meet both structural and functionals requirements. There are no sufficiently disclosed sequence variants having as little as 80% homology to SEQ ID NOs: 7, 8, 9, 10, 11 and/or 12 and the claimed functional properties listed above. Further, with regards to combinations of antibodies in the claims, the specification discloses results which show that only antibody combinations containing an Antibody Species A (labeled: NG1) had a clear difference in signal between the extracted sample solution containing Neisseria gonorrhoeae and the extracted sample solution containing Neisseria meningitidis (i.e. actually able to detect Neisseria gonorrhoeae without cross-reacting); and therefore the specification discloses that Antibody Species A is essential to generating an antigen-antibody reaction for the detection of Neisseria gonorrhoeae (see Example 2; Table 3 and [0114]). However, the full scope of the claims does not require Antibody A. The specification discloses that only the combination of an Antibody Species A (i.e. NG1) with Antibody Species B (i.e. NG3) was able to detect Neisseria gonorrhoeae at concentrations as low as 1 to 2e4 cfu/mL and that the combination of Antibody Species A with Antibody species C or D could not detect Neisseria gonorrhoeae at the same concentrations (e.g. see Example 2; Table 4 and [0122]). Similarly, the specification discloses that the combination of Antibody Species A with Antibody Species B showed good detection performance by ELISA, and was able to detect Neisseria gonorrhoeae at concentrations as low as 1 to 2e4 cfu/mL but that, in contrast, the combination of Antibody Species A with Antibody Species C failed to do so (e.g. see Example 4 and Table 5). Therefore, the specification provides evidence that there is unpredictability in the results obtained from species other than those specifically enumerated (i.e. not all of the combinations of disclosed antibodies worked as claimed), and accordingly, the evidence indicates ordinary artisans could not reliably predict the operability in the invention of any species other than the one disclosed (i.e. combination of Antibody NG1 with either NG2 or NG3). Accordingly, based on the unpredictability, the only way to determine if the functional property of a sequence fragment, derivative, and/or variant is indeed retained, is empirical testing of each and every option and/or combination 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, since testing such a vast number of options and combinations 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, detection of Neisseria gonorrhoeae was under development, and thus necessarily unpredictable, as evidenced by, for example, Verma et al. 2016 (Gonorrhoea diagnostics: An update; Indian Journal of Medical Microbiology 34(2):139-145) teaches diagnosis of gonorrhea is an ongoing challenge because the organism is fastidious and requires meticulous collection and transport and that there remains a need for the detection via culture and non-culture methods and Mahapure et al. 2023 (A Review of Recent Advances in Our Understanding of Neisseria gonorrhoeae; Cureus 15(8):e43464. DOI 10.7759/cureus.43464) which teaches Point of Care diagnostic tests (POCTs) for gonorrhoeae remains a significant goal (i.e. under development) to provide precise and rapid detection. Further, the functional characteristics of an antibody are determined by its complete structure, as evidenced by, for example, Sela-Culang et al. 2013 (The structural basis of antibody-antigen recognition; Frontiers in Immunology 4(302):1-13) which teaches the hypervariable loops within the variable domains of antibody polypeptides are widely assumed to be responsible for antigen recognition while the constant domains are believed to mediate effector activation, but that recent analysis indicates that their clear functional separation between the two regions is an over-simplification (see abstract). Sela-Culang teaches some residues within the CDRs may not participate in antigen binding and some residues outside the CDRs (e.g. in framework regions and in the constant domains) often contribute critically to the integration with the antigen (see abstract). Sela-Culang teaches understanding the role of each structural element is essential for successful engineering of binding polypeptides (e.g. page 2, left column). Sela-Culang teaches almost all of the residues predicted to be part of an epitope may be considered as correct predictors as they will bind to some antibodies but also are false predictors as they don' t bind to the others and accordingly that predicting that a residue is not in an epitope may be either a true negative or a false negative depending on the anybody considered (page 2, right column). Sela-Culang teaches each CDR has its own unique amino-acid composition different from the composition of the other CDRs and that each CDR has a unique set of contact preferences favoring certain amino acids over others (page 5-6, bridging). Sela-Culang et al. teach the combined action of all six CDRs is the evolutionary response of the immune system that enables the antibody polypeptide to recognize virtually any surface patch on the antigen (page 6). Thus, the state of the art supports that the skilled artisan requires guidance on the critical structures of the antibody per se and thereby does not provide adequate written description support for which structural features of the sequences would predictably retain their functional activity. Therefore, 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 partial structures 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 detection of Neisseria gonorrhoeae using the combination of Antibody A comprising SEQ ID NOs: 7 & 8 with Antibody B comprising either SEQ ID NOs: 9 &10 or 11 & 12, with the same functional properties, as broadly as is claimed. 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 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 kit for the detection of Neisseria gonorrhoeae comprising the combination of Antibody A with Antibody B) usually does not provide an adequate basis to support generic claims (i.e. all kits comprising all antibody fragments, derivatives, and/or sequence variants for the L7/L12 derived antigen and mixed-and-matched in haphazard combinations). 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 antibody fragments, derivatives, and 80% sequence variants, and accordingly, without such guidance, the experimentation left to those skilled in the art is unnecessarily and improperly extensive and undue. It is again noted that providing methods for determining the functional properties, would not reduce the amount of experimentation required because the functional properties still must be determined empirically. 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. antibody fragments, derivatives and/or 80% sequence variants, alone or in combinations), 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. Accordingly, it is the Office’s position that Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 102
11. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
12.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.
13. Claims 23-40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shirai et al. 2000 (CA 2 338 989; English equivalent of WO 2000/06603, of record) as evidenced by UniProt entry A0A1D3EQW6_NEIGO; 2016, see below).
Shirai teaches kits comprising sandwich ELISA (i.e. capture and detection antibodies on solid supports and with appropriate reagents) for Neisseria gonorrhoeae based on detection of the Neisseria gonorrhoeae ribosomal protein L7/L12 antigen using monoclonal antibodies made against the entire length or a partial sequence thereof (abstract; page 6; page 12; pages 23-24; and Examples 7-9; meeting limitations found in instant claims 23-28 and 37-40). Shirai teaches the monoclonal antibodies are used in ELISA, conventional immunochromatic methods, and/or sandwich assays (e.g. see page 17; meeting limitations found in instant claims 23 and 28).
With regards to the limitations “…wherein an efficiency in detecting the Neisseria gonorrhoeae-derived antigen more than 10 times higher than the efficiency in detecting a Neisseria meningitidis -derived antigen” in claims 29 and 30; and “…which does not cause a cross-reaction with bacteria of the genus Mycoplasma, the genus Escherichia, the genus Chlamydia, the genus Pseudomonas, the genus Staphylococcus, the genus Legionella, the genus Streptococcus in the sample” in dependent claims 31 and 32; and the sample types claimed in claims 33-36, none of these limitations appear to add a component to the kit and thus have each been interpreted as intended use limitations (see MPEP 2144.07). Nevertheless, Shirai teaches their antibodies did not cross-react with several species of bacteria, including Escherichia coli (e.g. see Tables 3 and 4).
Therefore, it is the Office’s position that the kits taught by the prior art are the same, or substantially the same, as the instantly claimed kits because they both are sandwich ELISAs which, by definition, use bound-capture antibodies and labeled-detection antibodies, and both use monoclonal antibodies raised against the same full length Neisseria gonorrhoeae L7/L12 antigen which would be a match to instant SEQ ID NO: 1 as evidenced by 2016 UniProt entry:
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99
812
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356
806
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However, the Office does not have the facilities for making and comparing the antibodies in Applicant’s kit (i.e. what the antibodies bind to) with those of the prior art reference; and thus, the burden is now upon the Applicant to show a distinction between the material structural and functional characteristics of their claimed kits with those of the prior art; See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594. Further, MPEP 2112.01 states that “When the PTO shows a sound basis for believing that the inventions of the Applicant and the prior art are the same, the Applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Accordingly, absent convincing evidence to the contrary, it is the Office’s position that Shirai anticipates the invention as claimed.
Conclusion
14. No claims are allowed.
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
February 25, 2026