Notice of Pre-AIA or AIA Status
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
The original claim set filed 6 May 2025 is acknowledged. Claims 1-21 are currently pending. No claims are cancelled. Claims 1-21 will be examined on the merits herein.
References to the Specification
The instant specification does not include paragraph numbers. To avoid ambiguity if future amendments to the specification change the page and line numbers where information is located, in this action references to the specification will use paragraph numbers from the Pre-Grant Publication US-20250262291-A1 (PTO-892).
Priority
This case claims priority to foreign priority document SE1651746-8 (filed 28 Dec 2016). Also, this case is CON of 18/212,857 (filed 22 June 2023), which is a CON of 16/474,940 (filed 28 June 2019), which is a 371 of PCT/SE2017/051323 (21 Dec 2017). Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 16/474,940, filed on 28 June 2019.
This application repeats a substantial portion of prior Application Nos. 18/212,857 (filed 22 June 2023)and 16/474,940 (filed 28 June 2019), and adds disclosure not presented in the prior application. For example, Table 1 of the instant specification (starts on pg. 17, [0117]) as filed 5/6/2025 says that the amounts indicated have the units of ug/mg total protein. However, in the priority documents and parent cases, the specs as filed say that the amounts in Table 1 have the units of ug/ug total protein. Because this application names the inventor or at least one joint inventor named in the prior application, it may constitute a continuation-in-part of the prior application. The priority designation on the filing receipt is objected to because the clear difference in units calls into question the 112(a) written description support for the purposes of priority. Unless corrected, the application is a CIP of the parent case.
It is noted that the amendment to convert ug to mg total protein was made in parent case 18/212,857 in the submission filed 9/20/24. Applicant successfully argued that the amendment is correcting a clear error to make the unit consistent with the other data presented in the specification. The evidence of the In re Oda (correction: mistake and correction are clear and thus not new matter) in the parent application does not carry over into this case. Nevertheless, as the difference between the current and priority specifications is akin to fixing a typographical error, the effective filing date used for searching claims 1-21 is 28 Dec 2016.
Information Disclosure Statement
The information disclosure statement filed 4 Sep 2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. Specifically, copies of the NPL documents #31 and 32 were not submitted with this action and could not be identified in the priority documents, so they were not considered. The copies of the other foreign patent and non-patent literature documents were submitted in Application Nos. 16/474,940 or 18/212,857. Other references have been considered by the examiner and a signed copy of the statement is attached with this action. Applicant is informed for future cases that 37 CFR 1.98(d) and MPEP 609.04(a) require that the IDS identify the prior application where copies were provided.
Claim Rejections - 35 USC § 112(a)
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 1-21 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. 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. This is a written description rejection.
MPEP 2163 states:
An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
The claims recite methods comprising administering to a subject a composition comprising a Streptococcus pneumoniae microparticle (MP), wherein said MP comprises: (i) the protein pneumolysin (Ply) at the level of ≥0.070 µg/mg total protein in the MP; (ii) the protein autolysin (LytA) at the level of ≥0.070 µg/mg total protein in the MP; (iii) the protein Pneumococcal surface protein C (PspC) at the level ≥0.130 µg/mg total protein in the MP; or (iv) the protein pilus-1 backbone protein (RrgB) at the level of ≥0.020 µg/mg total protein in the MP. Claim 1 requires only one of the four be present in the MP at the claimed level. Dependent claims 4 and 14-21 recite which specific proteins from (i)-(iv) must be present. Dependent claims 5-6 and 13 recite additional properties of the MP (diameter and amount of capsular polysaccharide present). Dependent claims 3 and 9-11 describe the formulation of the composition and intranasal administration.
The administration in claim 1 (and dependent claims) has the intended use of “inducing protective immunity against Streptococcus pneumoniae in a subject”. Claims 2, 7-8 and 12 recite additional in vivo functions that the composition performs after being administered.
The MPs used in the claimed method are broad: The claims are not limited to S. pneumoniae microparticles produced by any particular method. The MPs can be derived from any strain from the at least 97 serotypes of S. pneumoniae [0005]. Vesicles comprise many different proteins, such as the proteins disclosed in Tables 3-6 of the specification. The many proteins on the claimed MPs can be at any level (including absent), as long as at least one of the Ply, LytA, PspC, and RrgB proteins are above the claimed limit. The claims have a much lower limit of protein required by claiming the level of protein using units of µg/µg total protein rather than µg/mg total protein, which has dramatically increased the breadth of vesicles claimed. Therefore, the claims encompass a broad genus of MPs.
The specification teaches that membrane vesicles are only recently discovered and poorly understood in Gram-positive bacteria [0010].
MPs with elevated protein levels could be created in a variety of ways, including increasing protein expression by genetically modifying an isolate, choosing an isolate that naturally produces higher levels of the protein, changing the growth conditions, and others. For example, the specification demonstrates that the membrane vesicle Ply, LytA, PspC, and RrgB protein levels can be increased by growing S. pneumoniae TIGR4 or serotype 3 bacteria on solid media [0194]; compare the Ply, LytA, PspC, and RrgB protein levels in the solid culture “MP” vesicles with the liquid culture “MVL” vesicles (Table 1 at [0117]). The specification also demonstrates that the S. pneumoniae strain and serotype chosen affects the MP produced even when the bacteria are cultured and the MPs are isolated in the same way. In Table 1, both serotype 3 and 4 MP preparations have at least one of Ply, LytA, PspC, and RrgB with at least the claimed concentration; however, the two serotypes have different protein concentrations and only serotype 4 has RrgB proteins present in the MP. Additionally, recombinant overexpression of Ply, LytA, PspC, and/or RrgB in S. pneumoniae would generate microparticles with Ply, LytA, PspC, and/or RrgB above the claimed limits, regardless of the culturing method. Wingfield (2015; PTO-892) teaches that “The expression of recombinant proteins, especially using bacterial vectors and hosts, is a mature technology” and that “modest protein expression [is] (2% to 5% of the total cellular protein)” (pg. 1 col. 1 par. 1). Although all of the expressed protein may not enter the microparticle, 2% of the total protein (20 µg/mg) is so much higher than the claimed limits for Ply, LytA, PspC, and RrgB (≥ 0.020 - 0.130 µg/mg, depending on the protein) that MPs from cells engineered to overexpress one or more of these proteins must have at least the claimed levels of the overexpressed protein(s). Domingues et al. (2013; PTO-892) teaches that expression vectors for S. pneumoniae specifically were known well before the time of filing (Abstract).
However, the specification and the art teach that each method of making MPs would generate MPs with different properties. The specification measures the presence of proteins in solid-media and liquid-media-grown vesicle preparations and determines that many proteins differ between these growth conditions (compare Tables 3 and 4, or 5 and 6). While Ply, LytA, PspC, and RrgB are the only proteins where the change in concentration is quantified, the data of Tables 3-6 make clear that many proteins have different levels between these two conditions. Unlike the solid-culture-grown examples, recombinantly produced vesicles would have specifically increased levels of the protein(s) being expressed and would not have the broad changes in protein levels observed with solid-culture-grown MPs; see Domingues et al. Figure 4, which demonstrates that overexpressing RNAse R increases the mRNA and protein level of that specific protein, but does not affect the 16S rRNA or control protein levels.
It was also known in the art at the time of filing that vesicles produced by one serotype under one growth condition are not representative of vesicles produced by other serotypes under the same growth conditions. Olaya-Abril et al. (2014; PTO-892) teaches S. pneumoniae produces membrane vesicles when five different serotypes of S. pneumoniae are grown in liquid culture (Abstract, pg. 48 Sections 2.2-2.3), and identified proteins present in the vesicles (Table 2 on pg. 56, and Supplemental Datasets 3 and 4). Ply protein was only detected in 2/5 serotypes tested (ST6B and ST23F); LytA was not detected in any of the serotypes; PspC was only detected in 3/5 serotypes tested (R6, ST6B, and ST23F); and RrgB was not detected in any of the serotypes. Therefore, the work of Olaya-Abril teaches that different serotypes of S. pneumoniae produce different vesicles comprising different proteins even when the bacteria are grown in the same conditions; the results with one strain are not representative of what proteins will be present in another strain’s vesicles.
Excerpts from Olaya-Abril Supplementary Dataset 3, “EV” is extracellular vesicle data. Ply protein results highlighted first (2/5 serotypes had detectable protein in EVs). PspC results highlighted second (3/5 serotypes had detectable protein in EVs). LytA and RrgB were not detected.
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In contrast to the breadth of MPs that the claims state can be used in a method for inducing protective immunity against S. pneumoniae, the specification reduces to practice just two MP preparations (Table 1 at [0117]), derived by the method of growing S. pneumoniae strains TIGR4 or serotype 3 on solid media [0194]. The specification quantifies the level of Ply, LytA, PspC, and RrgB protein present in the MPs (Table 1 at [0117]). The specification teaches that the specific solid media microparticles provide protective immunity [Example 2, for example see [0190]].
The specification does not perform any experimentation to show that the level of Ply, LytA, PspC, and RrgB, either alone or in combination, is responsible for the claimed function of inducing protective immunity. There is no experimentation to rule out the effect on protective immunity being due to other properties of the solid media microparticles, such as the many other proteins that differ between liquid-media-grown and solid-media-grown vesicles [Tables 3-6]. Thus it is not clear that vesicle particles with only changes to one or more of Ply, LytA, PspC, and RrgB but not changes to those other proteins, such as vesicle particles produced by protein overexpression, would have the same protective effect when administered. The specification also does not perform any experimentation that shows that the specific minimal limit of Ply, LytA, PspC, and RrgB in the claims is critical for the effect.
The specification has demonstrated that the structure correlated with the function of “inducing protective immunity” is the two serotypes of solid-media-grown S. pneumoniae membrane vesicle microparticles, but that is not consistent with the currently claimed scope. Also, one of ordinary skill in the art would be aware that the specification’s method of administering the two serotypes of solid-media-grown microparticles to induce protective immunity, is not representative of the broad genus of claimed methods of administering a broad microparticles that only need to have changes in one protein chosen from Ply, LytA, PspC, and RrgB above a claimed limit because the claimed genus is so much broader than what was disclosed as being useful for the claimed effect.
Therefore, when evaluating the specification in the context of the prior art at the time of filing, one having ordinary skill in the art at the time of filing would have concluded that the specification demonstrated possession of vesicle microparticles made by the process of growing serotype 3 or 4 S. pneumoniae on solid media and methods of using them to induce protective immunity against S. pneumoniae, but have not demonstrated possession of methods of inducing protective immunity against S. pneumoniae using any vesicle microparticle where at least one of Ply, LytA, PspC, or RrgB is over the newly lowered claim limit. Therefore, claims 1-21 are rejected for failing to demonstrate possession of the claimed invention.
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 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,844,829. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claim 1, ‘829 claim 1 teaches an almost identical method; the difference is that the level of proteins claimed has units of μg/μg instead of μg/mg in the instant claims. The patented genus of protein levels is narrower and strictly within the currently claimed genus of protein levels, so the claim is anticipated.
Claims of 19/200,040
Claims of 11,844,829
1. A method for inducing protective immunity against Streptococcus pneumoniae in a subject, comprising administering to the subject a composition comprising a Streptococcus pneumoniae membrane vesicle microparticle (MP), wherein said MP comprises:
i. the protein pneumolysin (Ply) at the level of ≥0.070 μg/mg total protein in the MP;
ii. the protein autolysin (LytA) at the level of ≥0.070 μg/mg total protein in the MP;
iii. the protein Pneumococcal surface protein C (PspC) at the level of ≥0.130 μg/mg total protein in the MP;
or
iv. the protein pilus-1 backbone protein (RrgB) at the level of ≥0.020 μg/mg total protein in the MP.
1. A method for inducing protective immunity against Streptococcus pneumoniae in a subject, comprising administering to the subject a composition comprising a Streptococcus pneumoniae membrane vesicle microparticle (MP), wherein said MP comprises:
i. the protein Ply at the level of ≥0.070 μg/μg total protein in the MP;
ii. the protein LytA at the level of ≥0.070 μg/μg total protein in the MP;
iii. the protein PspC at the level of ≥0.130 μg/μg total protein in the MP;
or
iv. the protein RrgB at the level of ≥0.020 μg/μg total protein in the MP.
Regarding instant claims 2-3, 5-12, ‘829 claims 2-3 and 5-12 teach the identical text.
Regarding claims 4 and 13-21, ‘829 claims 4 and 13-21 teach the almost identical text. As with claim 1 above, the difference is that the level of proteins claimed has units of μg/μg instead of μg/mg in the instant claims. The patented genus of protein levels is narrower and strictly within the currently claimed genus of protein levels, so the claim is anticipated.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMELIA N DICKENS whose telephone number is (571)272-0381. The examiner can normally be reached M-F 8:30-4:30 (EDT/EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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AMELIA N DICKENS
Examiner
Art Unit 1645
/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
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