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 .
Claim Status
2. The amendment, filed 01/12/26, has been entered. Claims 41-42, 45-46, 51, 58-59, 61, 84-85, 87-94, and 98-103 are pending and under examination. Claims 1-40, 43-44, 47-50, 52-57, 60, 62-83, 86, 95-97, are cancelled. Claims 41 and 84 are amended.
Withdrawal of Objections/Rejections
3. The following are withdrawn from the Office Action, filed 07/10/25:
The rejection of claim 84 under 35 U.S.C. 112(d) as being of improper dependent, found on page 6 at paragraph 10, is withdrawn in light of Applicant’s amendments thereto.
Clarity of Record
4. In the interest of compact prosecution, it is noted that:
The cornerstone of the issue in this application focuses on the limitation “…wherein the number of O-acetyl groups per repeating unit of said conjugated capsular polysaccharide in said immunogenic conjugate is at least 0.6”.
The Office put forth multiple art rejections asserting that the naturally occurring chemical composition of the capsular polysaccharide of Streptococcus pneumoniae serotype 15B, includes O-acetyl groups and includes at least 0.7 mM of acetate per polysaccharide repeating unit; as evidenced by Venkateswaran et al. 1983 (Type Variation of Strains of Streptococcus pneumoniae in Capsular Serogroup 15; The Journal of Infectious Diseases, Volume 147, Issue 6, June 1983, Pages 1041-1054; see Table 3); and that consequently, absent required steps to alter the acetate and/or O-acetylation amounts, it was the Office's position that the prior art (Biemans WO 2012/119972 and/or Porro US 5,153,312) met the limitation because each prior art reference taught all of the positively recited steps in the claimed method (e.g. see Non-Final Office action, filed 11/28/22, paragraphs 6, 7; Final Office Action, filed 06/20/23, paragraph 6; Non-Final Office Action, filed 04/26/24, paragraph 10; and Final Office Action, filed 12/11/24, paragraph 9, page 5, page 8).
On page 10 of Remarks filed 06/11/25, Applicant asserted (emphasis added):
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Subsequently, the art rejections made in the Final Office Action, filed 12/11/24, were withdrawn based on these statements, which was fully explained in the Non-Final Office Action, filed 07/10/25, see paragraph 5.
Herein, Applicant appears to be changing their position with regards to the above statements as they were applied to non-art rejections made in the same Non-Final Office Action (see Responses to Arguments below).
However, Applicant cannot genuinely maintain both positions – therefore either the level of O-acetylation of the Streptococcus pneumoniae serotype 15B is naturally at least 0.7 mM of acetate per polysaccharide repeating unit as taught by Venkateswaran (in which case the Office reserves the right to re-institute the art rejections) unless something is done to increase or decrease the level; or the claimed method requires a particular strain of S. pneumoniae serotype 15B having this particular functional property (i.e. because the method would not work with all strains) or the method requires a positively recited step for a particular culture condition for all S. pneumoniae serotype 15B strains (i.e. because the method only works under specific culturing conditions).
In order to move prosecution forward, Applicant is requested to identify which position they currently hold and officially withdraw any Remarks that are contrary to that position
Maintained Rejection: Claim Rejections - 35 USC § 112
5. 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.
6. Claims 41-42, 45-46, 51, 58-59, 61, 84-85, 87-94, and 98-103 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.
Claim 41 is indefinite because it is unclear how “…the number of O-acetyl groups per repeating unit of said conjugated capsular polysaccharide…” can be anything less than an integer (i.e. a positive whole number) in general and/or “…is at least 0.6” (i.e. less than one complete O-acetyl group; and if less, what part of the group is included vs. excluded?). The same problem is found in claim 94.
Other dependent claims do not clarify the issues identified above. Therefore, clarification is required to remove the ambiguity of scope and clearly ascertain the metes and bounds of these claims.
Applicant’s Arguments and Response to Arguments
7. All of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record. For example:
With regards to the argument that the specification states that the presence of O-acetyl groups … is expressed as … the number of O-acetyl group per polysaccharide repeating unit on page 7 (see Remarks, page 6); the Office agrees and reproduces:
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However, this is argument is not persuasive because the above text does not clarify how the number of O-acetyl groups (i.e. a count) per repeating unit can be less than an integer and/or if a fraction of an O-acetyl group, then what fraction is included.
With regards to the Jones’ article (see Remarks, pages 6-7), and the multiple ways in which the degree of O-acetylation can be reported, the Office agrees that the Jones’ article expresses the amount of O-acetylation as a percentage (i.e. a ratio of numbers, but not a count thereof) and other art uses a molar ratio (i.e. a ratio of numbers, but not a count thereof). However, the percentage of repeating groups having an O-acetyl group (i.e. as reported by Jones) is not equivalent to the number of O-acetyl groups per repeating unit (i.e. not equivalent numbers). Thus, this is argument is not persuasive because the Jones article does not clarify how the number of O-acetyl groups (i.e. a count) can be less than an integer and/or if a fraction of an O-acetyl group, then what fraction is included.
Therefore, all of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record.
Maintained Rejection: Claim Rejections - 35 USC § 112
8. Claims 41-42, 45-46, 51, 58-59, 61, 84-85, 87-94, and 98-103 are rejected under 35 U.S.C. 112(b) as being incomplete for omitting essential steps, such omission amounting to a gap between the steps; See MPEP § 2172.01.
The omitted steps encompass: (a) the particular bacterial strain and/or (b) the particular growth conditions of a culture of Streptococcus pneumoniae serotype 15B bacteria, used to produce capsular polysaccharides that always necessarily have a value exceeding 0.6 O-acetyl groups per repeating unit.
These steps are deemed essential based on Applicant’s statements, including (a) “…the specification identifies acetate content as being one of the critical features of the structure of the polysaccharide, and emphasizes the importance of maintaining O-acetylation as the serotype 15B polysaccharide is sized, activated and conjugated with carrier protein”; (see Remarks, filed 06/11/25, page 9; emphasis added) and (b) “It cannot be ruled out, for example, that factors such as bacterial strain used or growth conditions of a culture of S. pneumoniae serotype 15B bacteria used to produce capsular polysaccharide could variably affect the extent of O-acetylation. Accordingly, it cannot be said that any particular batch of polysaccharide isolated from S. pneumoniae serotype 15B bacteria would necessarily have a value exceeding 0.6 O-acetyl groups per repeating unit.” (see Remarks, filed 06/11/25, page 10).
Accordingly, Applicant is not in compliance with 35 U.S.C. 112(b) because the missing steps are essential steps (i.e. identified as critical by Applicant).
Applicant’s Arguments and Response to Arguments
9. All of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record. For example:
With regards to the argument that “the rejection is entirely conclusory … it does not explain what term or limitation is vague or unclear such that a person of ordinary skill in the art would be uncertain as to the scope of the claims” (see Remarks, bottom of page 8); the Office disagrees and notes Applicant first reiterated the Office’s position see Remarks page 7:
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Followed by (top of page 8):
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Thus, this argument is not persuasive because it is not an accurate reflection of prosecution. For example, as shown above, Applicant acknowledges that the Office set forth what elements were deemed essential and missing (i.e. a particular bacterial strain and/or particular growth conditions) and the basis for concluding that these elements were essential (i.e. because Applicant said so – see boxed text). Further, with regards to Applicant’s assertion that the Office did not explain how Applicant’s remarks led to the conclusion (see Remarks page 9), the Office again disagrees and reminds Applicant that they explicitly stated that factors such as bacterial strain used and the growth conditions would variably affect the extent of the O-acetylation and that it could not be said that any particular batch of polysaccharide would necessarily have greater than 0.6 O-acetyl groups per repeating unit (i.e. that the method would not be expected to work for all strains and/or all culture conditions; see boxed text above). Therefore, Applicant has conceded these are essential elements (i.e. the particular bacterial strain and the particular growth conditions are required to lead to the claimed result) to the invention, yet they are not in the claims. Therefore, it remains the Office’s position that the claims are incomplete for omitting essential steps and such omission amounts to a gap between the steps; See MPEP § 2172.01.
With regards to Applicant’s assertion that the comments were taken out of context (Remarks, page 9), the Office has reproduced them above. Thus, this argument is not persuasive because it is not an accurate reflection of prosecution as the Office is using Applicant’s full text, verbatim.
With regards to the argument that (in an argument relating to inherent anticipation), Applicant explained that the prior Office action had not shown that capsular polysaccharide isolated from S. pneumoniae serotype 15B bacteria would necessarily contain at least 0.6 O-acetyl groups per repeating unit because it was possible that, e.g., bacterial strain or growth conditions could affect the degree of O- acetylation. But uncertainty as to whether any particular batch of polysaccharide isolated from S. pneumoniae serotype 15B bacteria would contain at least 0.6 O-acetyl groups per repeating unit does not make the claims indefinite absent steps reciting a particular strain of such bacteria or particular conditions for growing them (see Remarks, page 9, emphasis added) the Office disagrees and notes that is exactly what it means to be an essential step because otherwise the method does not work as claimed. Once again, Applicant’s statements support that in order for the skilled artisan to reliably practice the method (i.e. prepare an immunogenic conjugate having a polysaccharide with at least 0.6 O-acetyl groups per repeating unit), the skilled artisan needs to start with the correct bacterial strain (since not all work) and/or the correct culturing conditions (since not all work) because there would otherwise be uncertainty as to whether or not the claimed immunogenic conjugate would be predictably produced in any given batch, since both the bacterial strain and the growth conditions affect the degree of O-acetylation, as conceded by Applicant. Therefore, it remains the Office’s position that the claims are incomplete for omitting essential steps, such omission amounting to a gap between the steps; See MPEP § 2172.01.
With regards to the argument that the art demonstrated the existence of S. pneumoniae serotype 15B bacteria and growth conditions which, at least sometimes, were capable of yielding polysaccharide containing at least 0.6 O-acetyl groups per repeating unit, as well as analytical methods for determining the degree of O-acetylation, and so a person of ordinary skill in the art would be able to determine whether a particular batch of isolated polysaccharide contained at least 0.6 O-acetyl groups per repeating unit without regard to the particular bacteria or growth conditions used in its preparation (see Remarks, page 9, emphasis added); the Office notes that this argument supports the Office’s position because having to determine if the method works, after the fact, supports that the method, as claimed (i.e. without the essential elements) does not work for all strains and/or all growth conditions. Accordingly, these arguments are not persuasive.
With regards to the argument that the metes and bounds of the pending claims are not unclear (see Remarks, page 9); the Office notes that the 112(b) rejection is based on the claims being incomplete for omitting essential steps and such omission amounting to a gap between the steps; See MPEP § 2172.01. Thus, this argument is misguided.
With regards to the analogy with a robot (see Remarks, page 10) the Office does not agree that the situations are sufficiently similar noting that the instant claims do not rely on functional language; and the instant specification explicitly says presence of O-acetyl groups is “critical”; and Applicant’s remarks were not made in the context of characterizing a prior art reference but rather in characterizing what a person of ordinary skill in the art would understand. Further, the Office reminds Applicant that each application is analyzed on a case by case basis and the actions (e.g. objections, rejections, allowances, appeals, etc.) of one application do not dictate the actions made in other cases. Thus, this argument is not germane.
However, despite all of the above arguments, Applicant amended independent claim 41 to include a first step of "preparing a fermentation culture of Streptococcus pneumoniae serotype 15B bacterial cells capable of producing capsular polysaccharide with a degree of O-acetylation of at least 0.6 O-acetyl groups per repeating unit under conditions sufficient for such cells to produce capsular polysaccharide with said degree of O-acetylation (see Remarks, page 10 and claim 41). However, the Office does not deem the generic amendment sufficient because it does not include (a) the particular bacterial strain and/or (b) the particular growth conditions, as clearly set forth in the rejection. Consequently, it remains the Office’s position that the claims are incomplete for omitting essential steps and such omission still amounts to a gap between the steps; See MPEP § 2172.01.
Therefore, all of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record.
Maintained Rejection: Claim Rejections - 35 USC § 112
10. Claims 41-42, 45-46, 51, 58-59, 61, 84-85, 87-94, and 98-103 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 new matter rejection.
The amended claims encompass “…the number of O-acetyl groups per repeating unit of said conjugated capsular polysaccharide in said immunogenic conjugate is at least 0.6” (e.g. see claim 41 and a similar issue in claim 94, amended 06/11/25). However, the specification does not adequately describe wherein the number of O-acetyl groups is determined as a count (i.e. a number as compared to a molar ratio, see cited sections below) including wherein that very specific count is less than a whole number; and therefore these amendments constitute new matter.
Although the PTO has the initial burden of presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims, when filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP 714.02 and 2163.06 (“Applicant should therefore specifically point out the support for any amendments made to the disclosure.”). Applicant originally pointed to support for amendments to claim 41 at p. 7, Il. 1-18; p. 7, Il. 33-36; p. 12, Il. 26-27; p. 19, Il. 28-31 and p. 20, Il. 29-30. However, a review of these paragraphs reveals this particular limitation is not explicitly supported there (i.e. there no description of a number less than one group per repeating unit and/or what even constitutes a fraction of a group).
Accordingly, the limitations constitute new matter.
Applicant’s Arguments and Response to Arguments
11. All of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record. For example:
With regards to the argument that the instant specification and art cited in it contemplate three equivalent ways of expressing the degree of O-acetylation of capsular polysaccharide isolated from S. pneumoniae serotype 15B, i.e., as a molar ratio (number of mM acetate per mM polysaccharide), the number of O-acetyl group per polysaccharide repeating unit, or as the percent of repeat units which contain an O-acetyl group … and in view of this express equivalence between the formats one of ordinary skill in the art would readily understand Applicant’s disclosure (see Remarks, page 11); the Office notes that neither the specification or the art demonstrates how to convert the three ways (i.e. there are three different ways, but they are not equivalent as asserted by Applicant because, for example, 0.6 O-acetyl groups per repeating unit is not the same as 0.6 percent of the repeating units containing an O-acetyl group, the way that 6 grams/liter is equivalent to 6 milligrams/milliliter). Further, only the number of O-acetyl groups per repeating unit would be a whole number while the other two are ratios of numbers (and thus encompass numbers less than a whole number, such as 0.6). Thus, this argument is not persuasive because it does not point to support for a description of a limitation of “…the number of O-acetyl groups per repeating unit of said conjugated capsular polysaccharide in said immunogenic conjugate is at least 0.6” which allows less than a whole number of O-acetyl groups per repeating unit (and by extension an undescribed fraction thereof).
With regards to the argument that there is abundant disclosure that serotype 15B capsular polysaccharide in its isolated, activated and conjugated form can comprise at least 0.6 mM acetate per mM of capsular polysaccharide (e.g., p. 8, II. 20-29; p. 12, I. 34 to p. 13, I. 6; and p. 20, II. 29-36) Remarks, page 11; the Office disagrees and notes each of these citations is merely a boilerplate list of mM acetate per mM polysaccharides (i.e. a ratio) and none contain “…the number of O-acetyl groups per repeating unit of said conjugated capsular polysaccharide in said immunogenic conjugate is at least 0.6” or a positively recited method step that results in changing the O-acetyl groups from what naturally exists. Therefore, these arguments are not persuasive because they do not point to support for the limitations that allows less than a whole number of O-acetyl groups per repeating unit (and by extension an undescribed fraction thereof).
Therefore, all of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record.
Maintained Rejection: Claim Rejections - 35 USC § 112
12. Claims 41-42, 45-46, 51, 58-59, 61, 84-85, 87-94, and 98-103 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 process(es) for preparing an immunogenic conjugate comprising Streptococcus pneumoniae serotype 15B capsular polysaccharide covalently linked to a carrier protein, comprising the steps of:
(a) preparing a fermentation culture of Streptococcus pneumoniae serotype 15B bacterial cells capable of producing capsular polysaccharide with degree of O-acetylation at least 0.6 O-acetyl groups per repeating unit under conditions sufficient for such cells to produce capsular polysaccharide with said degree of O-acetylation;
(b) isolating from said culture capsular polysaccharide from Streptococcus pneumoniae serotype 15B bacterial cells;
(c) mechanically sizing said isolated Streptococcus pneumoniae serotype 15B capsular polysaccharide;
(d) activating said sized Streptococcus pneumoniae serotype 15B capsular polysaccharide with an oxidizing agent, forming an activated polysaccharide, wherein said activated polysaccharide has molecular weight between 150 kDa and 300 kDa;
(e) reacting said activated polysaccharide and carrier protein with a reducing agent in DMSO to form said immunogenic conjugate, wherein the number of O-acetyl groups per repeating unit of said conjugated capsular polysaccharide in said immunogenic conjugate is at least 0.6, and wherein said immunogenic conjugate has molecular weight between 3000 kDa and 20000 kDa.
Consequently, (1) the independent claim constitutes a "broad generic claim” based on the generically claimed strains of Streptococcus pneumoniae serotype 15B that are capable of producing capsular polysaccharide with degree of O-acetylation at least 0.6 O-acetyl groups per repeating unit under conditions sufficient for such cells to produce capsular polysaccharide with said degree of O-acetylation; together with the generically claimed means of sizing of saccharides; the generically claimed oxidizing agents; the generically claimed molecular weights of the activated polysaccharide; the generically claimed carrier proteins; the generically claimed reducing agents; and the generically claimed molecular weight of the conjugate; and (2) the claimed genus has substantial variation because of the numerous options and combinations of options permitted. However, it is the Office' s position that the method steps, in particular, bacterial cells capable of producing capsular polysaccharide with degree of O-acetylation at least 0.6 O-acetyl groups per repeating unit under conditions sufficient for such cells to produce capsular polysaccharide with said degree of O-acetylation have not been described with sufficient particularity, such that one skilled in the art would recognize that Applicant had possession of the full scope 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 (i.e. an immunogenic conjugate wherein the number of O-acetyl groups per repeating unit of said conjugated capsular polysaccharide in said immunogenic conjugate is at least 0.6) and the structures that meet those requirements (e.g. which bacterial strains, cultured under which conditions, and then sized by what means, and to what size, then activated by which oxidizing agents, coupled to which carrier proteins, and using with reducing agents, to reliably and predictably ensure that the polysaccharide component of the conjugate retains (or gains?) the required number of O-acetyl groups per repeating unit of at least 0.6; and/or (B) a lack of a representative number and variety of “species” (i.e. examples) 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 and variable genus of the claims because, inter alia, the specification does not disclose a correlation between the necessary structure of the starting Streptococcus pneumonia serotype 15B strain and/or the particular culture conditions and the claimed functional result (i.e. “critical features of the structure of the polysaccharide”; see Remarks, page 9) to be maintained including retaining (or gaining or reducing) the number of O-acetyl groups per repeating unit of the activated polysaccharide of the conjugate of at least 0.6.
The specification appears to describe methods for preparing a conjugate comprising fermenting and purifying serotype 15B capsular polysaccharides; sizing the saccharides by high pressure homogenization; oxidizing the polysaccharide using sodium periodate; verifying the size of the activated polysaccharide using SEC-MALLS; conjugating the activated polysaccharide to CRM197 using sodium cyanoborohydride and DMSO and then capping the unreacted aldehydes with sodium borohydride (see Example 1); wherein the conjugate so obtained has at least 0.6 mM acetate per mM of serotype 15B capsular polysaccharide. However, the specification does not adequately describe any positively recited steps to manipulate the final molar ratio of acetate to polysaccharide, in general, or the number of O-acetyl groups per repeating unit, specifically; and therefore these “critical features” must be there initially from the particular strain of bacteria and/or the particular culture conditions under which a strain was grown; but the specification does not adequately describe either. Further, the specification does not adequately describe a nexus between the use of high pressure homogenization and other means of mechanical sizing. The specification does not adequately describe a nexus between the use of sodium periodate and any other oxidizing agents. The specification does not adequately describe a nexus between CRM197 and any other carrier proteins. The specification does not adequately describe a nexus between the use of sodium cyanoborohydride and any other reducing agents, in general, and/or the use of cyanoborohydride, borohydride, sodium borohydride, zinc borohydride, amine borane, pyridine borane, 2-picoline borane, 2,6-diborane methanol, dimethylamine borane, t-BuMe/PrN-BHs, benzylamine-BHs, and 5-ethyl-2-methylpyridine borane, specifically. Consequently, it is the Office' s position that even one of skill in the art would not conclude that Applicant was in possession of the entire genus claimed based on a lack of structure-function correlations, known or disclosed.
In addition, the specification does not provide adequate written description to identify the broad genus of the claims because, inter alia, it does not describe a sufficient number and/or a sufficient variety of representative species (i.e. “examples”) to reflect the breadth and variation within the claimed genus. MPEP §2163 states 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 (as in the instant case), the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Further, MPEP §2163 states that 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) "[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 does not adequately describe a single proper example because the specification does not identify the particular strain used and/or the particular culture conditions used to ensure the resulting number of O-acetyl groups per repeating unit of the conjugated capsular polysaccharide in the immunogenic conjugate is at least 0.6, which appears to be in conflict with statements made by Applicant including “It cannot be ruled out, for example, that factors such as bacterial strain used or growth conditions of a culture of S. pneumoniae serotype 15B bacteria used to produce capsular polysaccharide could variably affect the extent of O-acetylation. Accordingly, it cannot be said that any particular batch of polysaccharide isolated from S. pneumoniae serotype 15B bacteria would necessarily have a value exceeding 0.6 O-acetyl groups per repeating unit.” (Remarks, page 10). Consequently, it is the Office's position that even one of skill in the art would not conclude that Applicant was in possession of the entire genus claimed based on a lack of number and/or variety of representative species described.
With regards to the state of the art, Venkateswaran et al. 1983 (Type Variation of Strains of Streptococcus pneumoniae in Capsular Serogroup 15; The Journal of Infectious Diseases, Volume 147, Issue 6, June 1983, Pages 1041-1054; see Table 3; of record) teaches Streptococcus pneumoniae serogroup 15B naturally contains at least 0.7 mM of acetate per polysaccharide repeating unit. Thus, in the absence of a positively recited step to remove or manipulate the amount of acetate, it seems the level would be maintained. However, Applicant is on record declaring that this is not the case (see Remarks, filed 06/11/25, page 10). Thus, the starting strain and/or the particular culture conditions must be essential elements and accordingly, must be adequately described.
In addition, Biemans (WO 2012/119972; of record, see previous art rejections) teaches methods for making multivalent conjugate vaccines via reductive amination comprising activating a saccharide via oxidation with periodate and reducing the activated saccharide in order to conjugate the saccharide to a carrier protein in the presence of DMSO (e.g. see abstract; and page 3, line 55 to page 4, line 20; and paragraphs 3 and 4); and teaches the polysaccharides are sized by known methods (e.g. see page 4, lines 47-53); and teaches the saccharide is derived from Streptococcus pneumoniae serotype 15B (e.g. page 4, line 45 to page 5, line 5; and paragraphs 6-9); and teaches the molecular weight of the saccharide is about 75-300 kDa (e.g. page 8, lines 4-10; and paragraphs 53-56); and teaches the carrier protein is CRM197 (e.g. page 5, lines 20-48; and paragraphs 16 and 17); and teaches the ratio of carrier protein to antigen is 0.4:1 to 2:1 (e.g. see page 7, lines 5-15; and paragraphs 37-39); and teaches the unreacted carbonyl groups maybe be capped using NaBH4 (e.g. page 7, lines 15-20; and paragraph 42) and even provides examples wherein 1-2 mg of saccharide was used (e.g. see Examples 1 and 2); and teaches the use of up to 100 mM phosphate buffers (e.g. see page 7, lines 35-45); and teaches the use of 0.1 to 0.3 molar equivalents of periodate oxidizing agent (e.g. page 7, lines 30-35); and teaches purifying the conjugates to remove the unconjugated (i.e. “free”) polysaccharides (e.g. page 21, lines 9-15) and provides an example of activation for 17 hours at temperatures of 20-25°C (e.g. see Example 1).
Similarly, Porro 1992 (US 5,153,312; of record, see previous art rejections) teaches methods of making multivalent vaccines comprising saccharide-protein conjugates, including those derived from Streptococcus pneumoniae serotype 15B, conjugated to CRM197 carrier proteins via reductive amination (i.e. defined as the activation of a polysaccharide by oxidation and the conjugation of the activated polysaccharide to a protein carrier by reduction; see instant specification page 10; and Porro Tables I and II; section 5.2; and Porro claims 11-17); and teaches reactions via the use of periodate, including periodic acid, and/or sodium cyanoborohydride (e.g. see Tables I and II; and columns 9 and 12); and teaches polysaccharides are adjusted in size to 200 to 2,000 kDa (e.g. see Table I and Figure 1); and teaches the use of DMSO (e.g. Figure 1; column 12); and teaches molar ratio of activated saccharide to carrier protein of 1:2 (e.g. see columns 12-13, bridging paragraph; and section 6.5.2); and teaches concentrations of the saccharide ranging from 1 to 5 mg/ml (e.g. see column 12 and section 6.4); and teaches activation in the presence of sodium cyanoborohydride followed by conjugation in the presence of DMSO at room temperature for 15 hours and/or at 4°C from 2 hours to overnight with longer periods increasing the yield of the reaction (e.g. see Table 1; and section 5.3); and provides explicit examples for the use of 0.01 M phosphate buffers (e.g. see section 6.5) and Porro teaches the glyco-conjugates are purified (e.g. column 13)
However, in both cases Applicant states “It cannot be ruled out, for example, that factors such as bacterial strain used or growth conditions of a culture of S. pneumoniae serotype 15B bacteria used to produce capsular polysaccharide could variably affect the extent of O-acetylation. Accordingly, it cannot be said that any particular batch of polysaccharide isolated from S. pneumoniae serotype 15B bacteria would necessarily have a value exceeding 0.6 O-acetyl groups per repeating unit.” Therefore, Applicant has declared that if a skilled artisan were to follow the steps taught by Biemans or Porro, the result would not be the same as the result obtained by Applicant. Thus, the art provides evidence that there is unpredictability in the results obtained from species other than those specifically enumerated, and accordingly, provides evidence which indicates even skilled artisans could not reliably predict the operability in the invention of any species other than the one disclosed (and in this case, there are none adequately described because the particular strain and/or culturing conditions are not included). Therefore, the state of the art does not provide adequate written description support for which options and which combinations would predictably retain their functional results; thus, the only way to determine if any given option or combination works is empirical testing of each and every option and/or combination of options.
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).
Applicant’s Arguments and Response to Arguments
13. All of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record. For example:
With regards to the argument that the specification discloses that "Serotype 15B Streptococcus pneumoniae strains may be obtained from established culture collections (such as for example ATCC deposit strain No ATCC10354 or strain available from the Streptococcal Reference Laboratory of the Center for disease control and prevention, Atlanta, GA)) or clinical specimens" (p. 5, II. 31-34) and additionally discloses that polysaccharide from such bacteria can be isolated by (a) preparing a fermentation culture, (b) lysing the bacterial cells in the culture, and (c) purifying polysaccharide from lysate (p. 5, II. 17-22) and that growing Streptococcus pneumoniae in fermentation culture is well known in the art (see Remarks, page 11); this appears to be in conflict with earlier statements regarding the essential nature of the both the strain and the culture conditions (see above). Thus, this argument is only persuasive if Applicant is conceding the starting strain is not essential, i.e., that the method would work with all Streptococcus pneumoniae strains of serotype 15B, in which case, the art rejections would be reinstated.
With regards to arguments pertaining to steps (b), (c), (d) (see Remarks, page 12-15); the Office reiterates that the specification does not adequately describe a nexus between the use of high pressure homogenization and other means of mechanical sizing. The specification does not adequately describe a nexus between the use of sodium periodate and any other oxidizing agents. The specification does not adequately describe a nexus between CRM197 and any other carrier proteins. The specification does not adequately describe a nexus between the use of sodium cyanoborohydride and any other reducing agents, in general, and/or the use of cyanoborohydride, borohydride, sodium borohydride, zinc borohydride, amine borane, pyridine borane, 2-picoline borane, 2,6-diborane methanol, dimethylamine borane, t-BuMe/PrN-BHs, benzylamine-BHs, and 5-ethyl-2-methylpyridine borane, specifically. questions the mixing and matching of the options within each with those of all the others. Thus, none of these arguments are persuasive because none of them adequately describe any positively recited steps to manipulate the final molar ratio of acetate to polysaccharide, in general, or the number of O-acetyl groups per repeating unit, specifically; and therefore it remains the Office’s position that these “critical features” must be there initially from the particular strain of bacteria and/or the particular culture conditions under which a strain was grown; but the specification does not adequately describe either. Thus, again, these arguments are only persuasive if Applicant is withdrawing earlier remarks and concedes that the method would indeed work with all strains of Streptococcus pneumoniae serotype 15B.
With regards to the argument that the specification reduced to practice the claimed method and properties of the resulting conjugates were compared with those prepared by reductive amination in DMSO, but using native (unsized) capsular polysaccharide, as well as conjugates prepared by reductive amination in aqueous buffer; and the inventors surprisingly discovered that conjugates prepared by reductive amination in DMSO retained most or all of the O-acetylation of the starting material, whereas conjugates prepared in buffer suffered a substantial reduction in degree of O-acetylation (see Remarks, page 15; emphasis added); Applicant is reminded that (a) reductive amination in DMSO is not in the independent claim and (b) both prior art references (Biemans and Porro) taught reductive amination in the presence of DMSO, to which Applicant argued that the prior art conjugates would not necessarily have the structural requirements of the claimed conjugate. Thus, this argument is only persuasive if Applicant is withdrawing previous statements.
With regards to the arguments that Applicant's earlier remarks were offered in the context of responding to an inherency rejection and to explain that the prior Office action had not shown that capsular polysaccharide isolated from S. pneumoniae serotype 15B bacteria would necessarily contain at least 0.6 O-acetyl groups per repeating unit. But that lack of certainty regarding degree of O-acetylation (which the Office action seems to recognize) does not mean the claims are not adequately described (or enabled). Because the claims are directed to methods, which do not need to "work" every time to be enabled, and the art admits of Streptococcus pneumonia serotype 15B bacteria and culture conditions which were capable of producing capsular polysaccharide with at least 0.6 O-acetyl groups per repeating unit sometimes, even if not necessarily every time, the specification need not disclose a "particular strain used and/or the particular culture conditions used" or "a positively recited step to remove or manipulate the amount of acetate" to adequately describe the claims. (see Remarks, page 17), the Office disagrees and notes that either the level of O-acetylation of the Streptococcus pneumoniae serotype 15B is naturally at least 0.7 mM of acetate per polysaccharide repeating unit as taught by Venkateswaran (in which case the Office reserves the right to re-institute the art rejections) unless something is done to increase or decrease the level; or the claimed method requires a particular strain of S. pneumoniae serotype 15B having this particular functional property (i.e. because the method would not work with all strains) or the method requires a positively recited step for a particular culture condition for all S. pneumoniae serotype 15B strains (i.e. because the method only works under specific culturing conditions); but all three options cannot be true. Therefore, to move prosecution forward, Applicant needs to identify which of the above is accurate (i.e. either the strain and culture conditions are essential or they are not; but if they are not, then the prior art of Porro and/or Biemans teaches the same positively recited steps and therefore the level of O-acetylation would indeed necessarily be the same as claimed).
Therefore, all of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record until clarification from Applicant is on the record.
Claim Rejections - 35 USC § 112
14. Claims 41-42, 45-46, 51, 58-59, 61, 84-85, 87-94, and 98-103 rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This is a biological deposit rejection.
Instant claims appear to employ a novel biological material, specifically a particular strain of Streptococcus pneumoniae serotype 15B that naturally and/or necessarily always has at least 0.6 O-acetyl groups per repeating unit after culturing, sizing, activating, and conjugating (i.e. see Remarks filed 06/11/25, page 10; “It cannot be ruled out, for example, that factors such as bacterial strain used or growth conditions of a culture of S. pneumoniae serotype 15B bacteria used to produce capsular polysaccharide could variably affect the extent of O-acetylation. Accordingly, it cannot be said that any particular batch of polysaccharide isolated from S. pneumoniae serotype 15B bacteria would necessarily have a value exceeding 0.6 O-acetyl groups per repeating unit.”). Since the biological material is essential to the claimed invention, it must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. If the biological materials are not so obtainable or available, the requirements of 35 U.S.C. 112 (a) may be satisfied by a deposit of the biological material.
If a deposit has been made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of deposit over his or her signature and registration number stating that the deposit has been accepted by the International Depository Authority under the provisions of the Budapest Treaty and that all restrictions upon public access to the deposit will be irrevocably removed upon the grant of a patent on this application. These requirements are necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State. Amendment of the specification to recite the date of the deposit and the complete name and full street address of the depository is required.
If a deposit has not been made under the provisions of the Budapest Treaty, then in order to certify that the deposits comply with the criteria set forth in 37 CFR 1.801-1.809, assurance regarding availability and permanency of the deposit is required. Such assurance may be in the form of an affidavit or declaration by applicants or assignees or in the form of a statement by an attorney of record that has the authority and control over the conditions of deposit over his or her signature and registration number averring:
during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request;
all restrictions upon the availability to the public of the deposited biological material will be irrevocably removed upon the granting of a patent on this application;
the deposits will be maintained in the public repository for a period of at least thirty years from the date of deposit or for the enforceable life of the patent of or for a period of five years after the date of the most recent request for the furnishing of a sample of the deposited biological material, whichever is longest;
a test of the viability of the biological material at the time of deposit will be made (See CFR 1.807); and
the deposit will be replaced if they should become nonviable or non-replicable.
In addition, a deposit of biological material that is capable of self-replication either directly or indirectly must be viable at the time of deposit and during the term of deposit. Viability may be tested by the repository. The test must conclude only that the deposited material is capable of reproduction. A viability statement for each deposit of biological material not made under the Budapest Treaty must be filed in the application and must contain:
The name and address of the depository;
The name and address of the depositor;
The date of deposit;
The identity of the deposit and the accession number given by the depository;
The date of the viability test;
The procedures used to obtain a sample if test is not done by the depository; and
A statement that the deposit is capable of reproduction.
As a possible means for completing the record, applicant may submit a copy of the contract with the depository for deposit and maintenance of each deposit.
If the deposit was made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the biological material described in the specification as filed is the same as that deposited in the depository. Corroboration may take the form of a showing a chain of custody from applicant to the depository coupled with corroboration that the deposit is identical to the biological material described in the specification and in the applicant’s possession at the time the application was filed. Applicant’s attention is directed to In re Lundack, 773 F.2d.1216, 227 USPQ (CAFC 1985) and 37 CFR 1.801-1.809 for further information concerning deposit practice.
Applicant’s Arguments and Response to Arguments
15. All of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record. For example:
With regards to the argument that the Office action has not established a prima facie case of lack of enablement because it did not undertake an analysis of the Wands factor, as mandated by court decisions and MPEP (see Remarks, page 17), Applicant is mistaken because this is a 112(a) Biological Deposit rejection (see MPEP 2402.01). Thus, this argument is not germane.
With regards to the argument that the rationale for finding an enablement defect rests on an incorrect understanding of Applicant’s remarks, (see Remarks, page 18) the Office reminds Applicant of what they wrote (reproduced above) and notes Applicant appears to now be changing their position on statements made that led to withdraw of art rejections. Applicant is also reminded that since the Office does not have the facilities for examining and comparing the O-acetylation of Applicant’s immune conjugates with those of any given prior art reference, the burden was properly shifted to Applicant to show a novel and unobvious distinction, to which the Remarks in question were made. Accordingly, the Office accepted Applications statements and withdrew the art rejections. If however, Applicant is now withdrawing these statements, then the Office reserves the right to reinstate those art rejections. Thus, these arguments are not persuasive because either the level of O-acetylation of the Streptococcus pneumoniae serotype 15B is naturally at least 0.7 mM of acetate per polysaccharide repeating unit, unless there is an active step to modify it; or the claimed method requires a particular strain of Streptococcus pneumoniae serotype 15B having this particular functional property (i.e. the method would not work with all strains) or the method requires a positively recited step for a particular culture condition for all Streptococcus pneumoniae serotype 15B strains (i.e. the method only works under specific culturing conditions). In the middle scenario (i.e. a particular strain is essential because not all strains have this property), the biological material is essential to the claimed invention, and therefore must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. It is the Office’s position that if the particular strain is required, then one way to satisfy the requirements of 112(a) is via a deposit, since it is otherwise not readily available to the public as it was not identified by Applicant. Thus, this argument is not persuasive in light of Applicant’s earlier statements.
With regards to the argument that the specification describes that "[s]erotype 15B Streptococcus pneumoniae strains may be obtained from established culture collections (such as for example ATCC deposit strain No ATCC10354 or strain available from the Streptococcal Reference Laboratory of the Center for disease control and prevention, Atlanta, GA)) or clinical specimens," the cells of which "are preferably grown in a soy based medium" and also describes how a skilled person could use art- recognized methods to lyse the bacteria, purify capsular polysaccharide from bacterial lysates and then quantify the degree of O-acetylation using a variety of methods and that the specification, therefore, provides the skilled artisan with all the disclosure necessary to isolate capsular polysaccharide from S. pneumoniae serotype 15B bacteria and then determine whether any particular preparation met the claimed requirement that "the number of O-acetyl groups per repeating unit of said conjugated capsular polysaccharide in said immunogenic conjugate is at least 0.6." (see Remarks pages 18-19); it is noted that these statements again appear to conflict with the earlier statements regarding the unpredictability in generating a polysaccharide with the claimed level of O-acetylation, including the essential nature of the particular strain, since not all strains would be expected to yield a polysaccharide with the claimed level of O-acetylation:
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Thus, this argument is not persuasive because it conflicts with the earlier statements that still require clarification in order to move prosecution forward.
Therefore, all of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record.
Conclusion
16. No claims are allowed.
17. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
18. 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.
19. 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.
20. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARY MAILLE LYONS/Examiner, Art Unit 1645
February 3, 2026