The previous Office action is vacated in lieu of that set forth below in order to correct the incorrect Application status on the Office action Summary page.
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 3-18-2026 is acknowledged. Claim 1 has been amended. Claims 20-22 have been added. Claims 1, 8-10, 13-14, 16-17 and 22 are pending. Claims 8 and 13 are hereby rejoined. Consequently, claims 1, 8-10, 13-14, 16-17 and 20-22 are currently under examination.
Claim Rejections Withdrawn
The new matter rejection of claims 1, 9-10 and 14-18 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of the amendment thereto.
Claim Rejections Maintained
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, 8-10, 13-14, 16-17 and 20-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement for essentially the reasons set forth in the previous Office action in the rejection of claims claims 1, 9-10, 14, 16-7 and 19. 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.
Applicant argues:
1. Applicant has amended independent claim 1 to recite a method of inducing an immune response to Streptococcus pneumoniae GAPDH utilizing a peptide that has at least 90% amino acid sequence identity with a peptide found within SEQ ID NO: 4 wherein said peptide is less than 50 amino acids in length and has an amino acid sequence with at least 90% identity to any one of SEQ ID NOs: 34-41.
2. The skilled artisan would recognize that Applicant had possession of the genus of claimed peptides that elicit antibodies to S. pneumoniae GAPDH because the sequences are derived from the GAPDH sequence from the bacteria S. pneumoniae itself, with only minimal variation in sequence allowed.
3. The present application teaches that peptides derived from bacterial GAPDH can elicit antibodies to the corresponding bacterial GAPDH protein, thereby establishing the structure-function relationship between GAPDH-derived peptides foreign to a host subject and the resulting function of eliciting antibodies to the corresponding GAPDH. Further, analysis of sequences with varied peptide sequences using software that detects epitopes shows the claimed peptides have good antigenicity.
4. As taught by the present application, GAPDH-derived peptides that are foreign to a host subject can elicit antibodies in a host. For instance, the specification shows that multiple GAPDH derived foreign peptides stimulate production of anti-GAPDH antibodies in Examples 7-8 of the application. These anti-GAPDH antibodies directly target S. pneumoniae GAPDH, and protect target neonatal animals against subsequent S. pneumoniae challenges in Example 10 of the application. Accordingly, the present application has established a clear structure-function relationship between GAPDH-derived peptides foreign to a host subject and the resulting function of eliciting antibodies to the corresponding GAPDH protein once the peptide is administered to the host subject, which conveys to the skilled artisan that Applicant was in possession of the claimed method.
5. Analysis of representative claimed peptide sequences by software also shows that a skilled artisan would recognize they are antigenic. The Kolaskar & Tongaonkar antigenicity analysis algorithm is well-established in the field for epitope analysis as of the filing date of the application.2 Exhibit A, appended below, shows antigenicity analysis of the claimed peptide sequences based on the Kolaskar & Tongaonkar antigenicity algorithm. For each of SEQ ID NO: 34-41, the algorithm provides antigenicity scores for each of the consecutive 7-amino-aicd segments in the peptide sequence. The 7-AA segments that are predicted to have high antigenicity are highlighted in Exhibit A. All claimed peptide sequences of SEQ ID NO: 34-41 contain segments that are predicted to be antigenic. The fact that the claims require at least 90% identity to SEQ ID NOS: 34-41, and thus allow for amino acid changes, does not disturb this analysis.
6. Exhibit B shows variations of up to 10% introduced into peptide sequences from one of SEQ ID NOs: 34-41, and confirms they contain epitopes. Exhibit B appended below introduces an alanine substitution into the claimed peptide sequence of SEQ ID NO: 36 and shows that antigenic epitopes are still present.
7. Additional peptides encompassed by the claim would be recognized by a skilled artisan as antigenic because the claimed peptide genus encompasses longer peptides (e.g., GAPDH-derived peptides that are 30 or 40 amino acids in length). The skilled artisan would recognize that additional epitopes would be contained in the additional portions of the proteins, and that they would help elicit antibodies to Streptococcus pneumoniae GAPDH.
Applicant’s arguments have been fully considered and deemed non-persuasive.
With regard to Points 1 and 2, the amendment is insufficient to overcome the rejection as there is still no correlation between structure (sequence) and function (i.e. to elicit a directed immune response against S. pneumoniae GAPDH. While the skilled artisan would be able to envision the sequences of peptides encompassed by the rejected claims, they would not be able to predict which of those peptides would elicit antibodies that bind to S, pneumoniae GAPDH. Moreover, the peptides encompassed by the instant claims are not limited to peptides with a 10% variation to the sequences of SEQ ID NO:34-41 but encompass any peptide that is less than 50 amino acids in length that contain a sequence of SEQ ID NO:34-41 (or variant thereof). Given that the tertiary structure of a given antigen is paramount to the ability of said antigen to be recognized and processed by the immune system, the skilled artisan would not be able to predict which (if any) of said peptides would be able to induce antibodies to S. pneumoniae GAPDH.
With regard to Points 3-4, the specification refers the ability of the peptides of SEQ ID NO:34-41 to induce antibodies in a generalized and prophetic sense but is limited to the use of the “Neonatal Vaccine” (which consist of the peptides consisting of SEQ ID NO:9-12 conjugated to a KLH or OVA carrier protein) and antibodies raised against said vaccine. Peptides 1 and 2 (SEQ ID NO:9 and SEQ ID NO:10) are native sequences from GBS, S. aureus and S. pneumoniae while Peptides 3 and 4 (SEQ ID NO:11 and SEQ ID NO:12) are native sequences form E. coli, K. pneumoniae and/or P. aeruginosa. Moreover, while the specification states:
“These peptides are illustrative of many more GAPDH peptides that may be found amongst the surface peptides of the bacteria, and used to create a vaccine of the
invention. Any peptide sequence within the native sequence may be used, but the sequence must not be substantively shared by GAPDH in humans.”
it is silent with regard to the efficacy of any other peptides derived from GAPDH that has efficacy in eliciting a directed immune response (i.e. antibody production) against the GAPDH of any bacterial species. The specification is equally silent with regard to the efficacy of any variant of Peptides 1-4 in eliciting a directed immune response against S. pneumoniae. Such a limited disclosure cannot be extrapolated to the use of any and all peptides and their variants encompassed by the claim for the production of antibodies to S. pneumoniae GAPDH. Therefore, contrary to Applicant’s assertion, the required structure-function is lacking.
With regard to Points 5 and 6, the Kolaskar & Tongaonkar reference discloses a “semi-empirical” method of epitope mapping. As evidenced by said reference, their predications were only 75% accurate and had to be tested for accuracy. Moreover, the predicted “epitopes” were all in the context of the total protein. Given, that the instant claims are not limited to a variation of a stable sequence (i.e. the sequences of SEQ ID NO:34-41) but encompass any peptide that is less than 50 amino acids in length that contain a sequence of SEQ ID NO:34-41 (or variant thereof). Consequently, the algorithm of the Kolaskar & Tongaonkar would not be able to “predict” which peptides in the claimed genus would be able to induce antibodies would have the claimed immunological characteristics. Given that the tertiary structure of a given antigen is paramount to the ability of said antigen to be recognized and processed by the immune system, the skilled artisan would not be able to predict which (if any) of said peptides would be able to induce antibodies to S. pneumoniae GAPDH. Finally, Applicant is reminded that 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.
With regard to Point 7, the instant claims are not limited to fragments of the S. pneumoniae GAPDH (i.e. SEQ ID NO:4) that are less that 50 amino acids in length that contain a sequence of SEQ ID NO:34-41 (and variants thereof) but any peptide that is less than 50 amino acids in length that contain a sequence of SEQ ID NO:34-41 (or variant thereof) regardless of the sequences flanking the sequences of SEQ ID NO:34-41 (or variants thereof).
The instant claims are drawn to methods of inducing a directed immune response to Streptococcus pneumoniae GAPDH utilizing a peptide with at least 90% amino acid sequence identity with a peptide found within SEQ ID NO:4 wherein said peptide less than 50 amino acids in length and has at least 90% sequence identity to SEQ ID NO:34-41. The specification provides insufficient written description to support the genus encompassed by the claim since, as evidenced by the specification, there is variability between the sequences of various SEQ ID NO:4 or SEQ ID NO:34-41 based peptides, the specification does not support the genus (peptides with the recited sequence homologies) encompassed by the rejected claims.
To fulfill the written description requirements set forth under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. To adequately describe the genus of peptides, Applicant must adequately describe which peptides (if any) have efficacy in eliciting a directed immune response against S. pneumoniae GAPDH. The specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of antibodies to which the claims are drawn, such as a correlation between the structure of the peptide and its recited function (inducing a directed immune response against S. pneumoniae GAPDH), so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of peptides. The specification fails to disclose what peptide sequences are essential for the induction of a given directed immune response, or which amino acids might be added, replaced or deleted so that the resultant domain peptide retains the binding specificity of its parent, or by which other amino acids the essential amino acids might be replaced so that the resultant peptide retains the binding specificity of its parent. Therefore, the specification fails to adequately describe at least a substantial number of members of the genus of peptides to which the claims refer.
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.).
Additionally, the rejected claims require that the recited peptides have efficacy in eliciting a directed immune response (i.e. antibody production) against S. pneumoniae GAPDH. To fulfill the written description requirements set forth under 35 USC § 112, first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. As set forth supra, the specification fails to adequately describe at least a substantial number of members of the genus of peptides to which the claims refer; and accordingly the specification fails to adequately describe at least a substantial number of members of the claimed genus of peptides. The specification does not provide substantive evidence that the claimed peptides are capable of inducing any type of directed immune response against S. pneumoniae GAPDH. This demonstration is required for the skilled artisan to be able to use the claimed peptides for their intended purpose of preventing/preventing S. pneumoniae infections. Without this demonstration, the skilled artisan would not be able to reasonably predict the outcome of the administration of the claimed peptides, i.e. would not be able to accurately predict if a given directed immune response has been induced. The specification is limited to characterizing the immunological characteristics of their “Neonatal Vaccine” (which consist of the peptides consisting of SEQ ID NO:9-12 conjugated to a KLH or OVA carrier protein) and the use of antibodies raised against said vaccine in animal studies. Peptides 1 and 2 (SEQ ID NO:9 and SEQ ID NO:10) are native sequences from GBS, S. aureus and S. pneumoniae while Peptides 3 and 4 (SEQ ID NO:11 and SEQ ID NO:12) are native sequences form E. coli, K. pneumoniae and/or P. aeruginosa. While the specification states:
“These peptides are illustrative of many more GAPDH peptides that may be found amongst the surface peptides of the bacteria, and used to create a vaccine of the
invention. Any peptide sequence within the native sequence may be used, but the sequence must not be substantively shared by GAPDH in humans.”
it is silent with regard to the efficacy of any other peptides derived from GAPDH or any variants thereof that have efficacy in preventing an infection by any sepsis-inducing bacterial species or inducing any type of directed immune response against S. pneumoniae. The specification is equally silent with regard to the efficacy of any variant of Peptides 1-4 in binding S. pneumoniae GAPDH. Such a limited disclosure cannot be extrapolated to the use of any and all peptides and their variants encompassed by the claim for the prevention of infections by any and all sepsis-inducing bacteria.
This disclosure cannot be extrapolated to the claimed genus of peptides as the ability to reasonably predict the capacity of a single bacterial immunogen to induce a given immune response from in vitro studies is problematic. As evidenced by the teachings of Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000), the art is unpredictable. Skolnick et al. 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 peptide would necessarily have a given immunological property. The instant specification has failed to teach or disclose compositions comprising the claimed SEQ ID NO:4 and 34-41-based peptides that are capable of eliciting any type of directed immune response against S. pneumoniae. There is no disclosure of subjects that have been administered any of the claimed peptides who have developed any type of directed immune response against S. pneumoniae. Consequently, there is no correlation between structure and function as required by the Written Description requirement.
Therefore, because the art is unpredictable, in accordance with the MPEP and current case law, the description of claimed peptides is not deemed representative of the genus of peptides to which the claims refer.
New Grounds of Rejection
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 8, 13 and 21 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.
Claim 8 is rendered vague and indefinite by the use of the phrase “…with at least 95% amino acid sequence identity to any one of SEQ ID NO:34-41”. It is unclear what is meant to be engendered by said phrase as a 5% deviation of any of the sequences of SEQ ID NO:34-41 is less than one amino acid. As written, it is impossible to determine the metes and bounds of the claimed invention.
Claim 21 is rendered vague and indefinite by the use of the phrase “…with at least 95% amino acid sequence identity with the peptide found in SEQ ID NO:4”. It is unclear what is meant to be engendered by said phrase as the peptide of SEQ ID NO:4 is limited by claim 1 to the peptides of SEQ ID NO:34-41 and a 5% deviation of any of the sequences of SEQ ID NO:34-41 is less than one amino acid. As written, 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.
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/ROBERT A ZEMAN/Primary Examiner, Art Unit 1645 May 11, 2026
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