The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment filed on 3-17-2026 is acknowledged. Claim 1 has been amended. Claims 2-3 6, 11-16, 19-20 and 24-26 have been canceled. Claims 91-120 have been added. Claims 1, 4, and 91-120 are pending. Claims 92-102 and 104-120 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 4, 91 and 103 are currently under examination.
Information Disclosure Statement
The Information Disclosure Statement filed on 3-17-2026 has been considered. An initialed copy is attached hereto.
It should be noted that the listing of references in the specification is not a proper information disclosure statement. 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, they have not been considered.
Claim Objections Withdrawn
The objection to claim 24 under 37 CFR 1.75 as being a substantial duplicate of claim 19 is withdrawn. Cancellation of said claim has rendered the objection moot.
The objection to claims 3 and 6 for containing claim language drawn to non-elected inventions is withdrawn. Cancellation of said claims has rendered the objection moot.
Claim Objections Maintained
Claims 1, 4 and 91 are objected to for containing claim language drawn to non-elected inventions.
New Claim Objections
Claims 1, 4, 91 and 103 are objected to for utilizing the abbreviation for the genus “Mycoplasma” with out defining it upon its first recitation.
Claims 1, 4, 91 and 103 are objected to for utilizing improper abbreviations for the genus Mycoplasma. The abbreviation “M” should read “M.”.
Claim Rejections Withdrawn
The rejection of claim 6 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being rendered vague and indefinite by its reference to specific amino acid residues is withdrawn. Cancellation of said claim has rendered the rejection moot.
The rejection of claims 1, 3-4, 6, 19 and 24 under 35 U.S.C. 102(a)(1) as being anticipated by Grover et al. (WO 2014/014897 – IDS filed on 8-1-2023) is withdrawn in light of the amendment thereto.
Claim Rejections Maintained
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 91 and 103 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 18/264,136 (reference application).
Applicant argues:
1. None of the claims of the '136 Application recites a modified mycoplasma protein M with mutations at the residues listed in amended claim 1.
Applicant’s arguments have been fully considered and deemed non-persuasive.
With regard to Point 1, there is no limitation to the “one or more amino acid mutations” encompassed by claims 1-6 of the copending application. Consequently, they necessarily encompass the specific mutations recited in the rejected claims.
As outlined previously although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to modified mycoplasma protein M or functional fragments thereof wherein the mycoplasma protein M can be from Mycoplasma genitalium or Mycoplasma pneumoniae.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4, 91 and 103 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 for the reasons set forth in the previous Office action in the rejection of claims 1, 3-4, 6, 19 and 24. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to modified mycoplasma protein M (or functional fragment thereof) wherein the modified mycoplasma protein M comprises one or more amino acid mutations wherein the one or more mutations are at residues selected from: a) 237; b) 232; c) 282; d) 150, 196, 198; e) 400,402, 407, 409, 413, 435; f) 373, 400; g) 402, 407, 409, 413; h) 342; i) 150, 196, 198, 232, 237, 282, 342, 373, 400, 402, 407, 409, 413, 435; j) 274; k) 150, 196, 198, 232, 237, 342; 1) 400, 402, 407, 409, 413, 435, 373; m) 205; n) 355; o) 150, 196, 198, 373, 400, 342; p) 373, 400, 150, 196, 198, 232, 237, 342; q) 201, 224; r) 150, 196, 198, 232, 237, 342, 201, 224; s) 150, 196, 198, 232, 237, 342, 390, 444; t) 150, 196, 198, 232, 237, 342, 201, 224, 274, 205, 355; u) 150, 196, 198, 232, 237, 342, 391; v) 468; w) 150; x) 300; y) 156; or z) 225 of M. genitalium protein M (SEQ ID NO: 1) or the equivalent residues of M. pneumoniae protein M (SEQ ID NO:23) or a functional fragment thereof. The rejected claim optionally require: the modified mycoplasma protein M or a functional fragment is from about residue 74 to about residue 479 of the M. genitalium protein M (SEQ ID NO:3) or the equivalent residues of M. pneumoniae protein M (SEQ ID NO:23)(claim 4); that the one or more mutations are selected from: a) F237T; b) S232Q or S232L; c) Q282D; d) S150E, S196R, S198P; e) V400I, N402I, K407P, S409V, L413I, T435I; f) V373I, V400I; g) N402L, K407P, S409V, L413I; h) A342V; i) S150E, S196R, S198P, S232Q, F237T, Q282D, A342V, V373I, IV400I, N402I, K407P, S409V, L413I, T435I; j) N274D; k) S150E, S196R, S198P, S232Q, F237T, A342V; l) V400, N402I, K407P, S409V, L413I, T435I, V373I; m) A205P; n) T355D, T355P, or T355G; o) S150E, S196R, S198P, V373I, V400I, A342V; p) V373I, V400I,S150E, S196R, S198P, S232Q, F237T, A342V; q) 5201 C, A224C; r) S150E, S196R, S198P, S232Q, F237T, A342V, 5201C, A224C; s) S150E, S196R, S198P, S232Q, F237T, A342V, F390E, Y444K; t) S150E,S196R, S198P, S232Q, F237T, A342V, 5201C, A224C, N274D, A205P, T355P; u) S150E, S196R, S198P, S232Q, F237T, A342V, A391P; v) R468Q; w) S150E; x) N300Q; y) S156K; or z) K225P of the M. genitalium protein M (SEQ ID NO: 1) or the equivalent residues of the M. pneumoniae protein M (SEQ ID NO:23) (claim 91); or wherein the one or more mutations comprise S150E,S196R, S198P, S232Q, F237T, and A342V of M. genitalium protein M (SEQ ID NO: 1) or the equivalent residues of M, pneumoniae protein M (SEQ ID NO: 23)(claim 103).
However, since the baseline sequence for any given “functional fragment” is variable, none of the recited compositions meet the written description provision of 35 USC 112, first paragraph as the recited amino acid positions do not correlate any particular residue except in relation to the full length sequence of SEQ ID NO:1. Moreover, given the instant claims encompass an incalculable number of mutations, the specification provides insufficient written description to support the genus encompassed by the claims.
To fulfill the written description requirement, Applicant must describe the sequence of the unmutated mycoplasma protein M fragment which would have a given “function” but also describe which mutations which would result/maintain the claimed biological activity. With the exception of the few mutants set forth in Figures 15 and 16, the specification is silent with regard to which combination of mutations would result in a mycoplasma M protein with the claimed characteristics and is completely silent with regard to the sequence of any “functional fragments”. Additionally, the specification defines a “functional fragment” as:
“…is one that substantially retains at least one biological activity normally associated with that polypeptide (e.g., antibody binding). In "functional fragment" substantially retains all of the activities possessed by the unmodified polypeptide. By "substantially retains" biological activity, it is meant that the polypeptide retains at least about 20%, 30%, 40%, 50%, 60%, 75%, 85%, 90%, 95%, 97%, 98%, 99%, or more, of the biological activity of the native polypeptide (and can even have a higher level of activity than the native polypeptide).”.
Consequently, the instant claims encompass a myriad of fragments of the polypeptides of SEQ ID NO:1 and/or SEQ ID NO:23 which must retain a given unnamed function.
MPEP § 2163.02 states, “[a]n 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' ”. The courts have decided:
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). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and 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.
MPEP 2163.02 further states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by 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); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); 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"). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Additionally, MPEP 2163 states:
"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)”
And:
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
Given the lack of a specific baseline sequence for the unmodified mycoplasma protein M fragment or recitation as to what “function must be maintained” there is no correlation set forth in the specification between structure and function as required by the written description requirements.
Protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Bowie et al (Science, 1990, 257:1306-1310) teach that an amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex. (column 1, page 1306). Bowie et al further teach that while it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three-dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions (column 2, page 1306). The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al (J. of Cell Bio. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Molecular and Cellular Biology, 1988, 8:1247-1252) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein. Bork (Genome Research, 2000, 10:398-400) disclose that protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2). Clearly, given not only the teachings of Bowie et al., Lazar et al. and Burgess et al. but also the limitations and pitfalls of using computational sequence analysis and the unknown effects of alternative splicing, post translational modification and cellular context on protein function as taught by Bork, the functional variants of the polypeptide of SEQ ID NO:1 (and variants and fragments thereof) cannot be predicted. Clearly, it could not be predicted that a polypeptide that is a “variant” of a given SEQ ID NO: will function in a given manner. Reasonable correlation must exist between structure and function. In the instant case there is no correlation between the structure (i.e. sequence) of a given modified mycoplasma protein M and its recited function (inducing increased or unaltered thermostability). The specification, however, fails to disclose which amino acid residues of a given modified mycoplasma protein M fragment are essential for the reciting biological functions or which amino acids might be added, replaced or deleted so that the resultant polypeptide retains the immunological characteristics of its parent, or by which other amino acids the essential amino acids might be replaced with so that the resultant peptide retains the Applicant must describe the sequence of the unmutated mycoplasma protein M but also describe which mutations which would result in the claimed biological activity. With the exception of the few mutants set forth in Figures 15 and 16, the specification is silent with regard to which combination of mutations would result in a mycoplasma M protein with the claimed characteristics. Consequently, the specification, does not disclose distinguishing and identifying features of a representative number of members of the genus of modified mycoplasma protein M to which the claims are drawn, such as a correlation between the structure of the modified mycoplasma protein and its recited function, so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of antibodies. As evidenced by the teachings of Skolnick et al., the art is unpredictable. Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000) discloses the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (see, e.g., the abstract; and page 34, Sequence-based approaches to function prediction). 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 the function of the structurally related protein (see, in particular, the abstract and Box 2). Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence, that a variant of a given polypeptide would necessarily possess a given biological characteristic.
Given the skilled artisan would not be able to predict whether a given modified mycoplasma protein M fragment would have the claimed characteristics, there is no correlation between structure and function as required by the written description requirements. Consequently, proper written description is lacking.
New Claim Rejections
35 USC § 112
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.
Claims 1, 4, 91 and 103 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Said claims are rendered vague and indefinite by its reference to specific amino acid residues in terms of “functional fragments”. Without a baseline sequence for unmodified PfRH5 antigen fragment, the recited residues have no definitive meaning. Consequently, it is impossible to determine the metes and bounds of the claimed invention.
Conclusion
No claim is allowed.
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).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT A ZEMAN whose telephone number is (571)272-0866. The examiner can normally be reached Monday thru Friday; 6:30 am - 3pm EST.
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/ROBERT A ZEMAN/Primary Examiner, Art Unit 1645 May 21, 2026
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