DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicants ‘amendments and response of 10/7/2025 are acknowledged. Claims 1 has been amended. Claims 2-3 and 13 have been canceled.
Status of the Claims
3. Claims 1, 4-12, 16-17, 19 and 21 are pending. Claims 1 has been amended. Claims 2-3, 13 and 18 have been canceled. Claims 14-15 and 20 have canceled.
Drawings
4. The drawings filed 12/7/2022 are accepted by the examiner.
Information Disclosure Statement
5. Information disclosure statement filed 12/7/2022 is acknowledged. Initialed copy is enclosed. The listing of references in the specification (pages 66-69) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Election/Restrictions
6. Applicants’ election without traverse of 10/7/2025 is acknowledged. Applicants elected group I claims 1, 4-12 and 16 directed to a protein nanoparticles conjugated to bacterial saccharides and immunogenic composition.
Claims 1, 4-12 and 16 are under consideration. Claims 17, 19 and 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected inventions.
Claim Objections
7. Claims 5 and 7 are objected to because of the following informalities:
Claims 5 and 7 recite abbreviations EDAC, EDC, CDAP and VLP. Full names of said abbreviations are required when they are recited first time in the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
8. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
9. Claims 1, 4-12 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over EP-3 650 044 A1, (5/13/2020) in view of Kapre (US 2017/0072043 A1 filed 9/12/2026) and further in view of Steinmetz et al. (WO 2018085658 A1 priority to 11/3/2026).
The clams are drawn to:
Claim 1. A protein nanoparticle having an antigenic molecule conjugated to its exterior surface, wherein the antigenic molecule is a bacterial saccharide, and wherein the bacterial saccharide is from a Streptococcus species, wherein the Streptococcus species is Streptococcus agalactiae ("Group B Streptococcus" or "GBS") or Streptococcus pneumoniae.
Claim 4. The protein nanoparticle of claim 1, wherein the bacterial saccharide is conjugated directly to the protein nanoparticle or via a spacer (linker) group.
Claim 5. The protein nanoparticle of claim 1, wherein the bacterial saccharide is conjugated to the protein nanoparticle by a method selected from the group consisting of (a) reductive amination; (b) carbodiimide chemistry (for example EDAC OR EDC); (c) maleimide chemistry; and (d) cyanylation chemistry (for example CDAP).
Claim 6. The protein nanoparticle of claim 1, wherein the protein nanoparticle is a non-viral protein nanoparticle.
Claim 7. The protein nanoparticle of claim 1, wherein the protein nanoparticle is a bacteriophage VLP, wherein the bacteriophage VLP is a Qbeta VLP.
Claim 8. The protein nanoparticle of claim 1, wherein the protein nanoparticle comprises a subunit polypeptide having at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, or SEQ ID NO: 11, wherein the subunit protein is capable of self-assembling to form the nanoparticle.
Claim 9. The protein nanoparticle of claim 1, wherein the protein nanoparticle is capable of eliciting a higher immune response to the bacterial saccharide after one
dose compared to after one dose of a monomeric protein carrier, such as CRM197, conjugated to the same bacterial saccharide.
Claim 10. The protein nanoparticle of claim 1, wherein the protein nanoparticle is capable of eliciting a higher or comparable immune response to the bacterial saccharide after one dose compared to after two doses of a monomeric protein carrier, such as CRM197, conjugated to the same bacterial saccharide.
Claim 11. An immunogenic composition comprising at least one protein nanoparticle according to claim 1.
Claim 12. The immunogenic composition of claim 11, further comprising an adjuvant.
Claim 16. The protein nanoparticle of claim 1, wherein the protein nanoparticle induces an immune response in a subject.
EP-3 650 044 A1 discloses the conjugation of bacterial capsular polysaccharides (CPS) to virus-like particles (throughout, e.g. [0017], [0018], claims 1, 4). EP-3 650 044 A1 suggests to use CPS from Streptococcus ([0042], claim 9), and the use of capsids from bacteriophages [0063], [0064], attachment by reductive amination, and production of the VLP particles in cells [0030]- [0034]. As exemplary VLP monomers, EP-3 650 044 A1 suggests to use any of SEQ ID NOs. 8-18 ([0046], claim 12), wherein SEQ ID NO. 11 is identical to SEQ ID NO. 1 of the present application. EP-3 650 044 A1 also discloses corresponding uses as vaccines, including single-dose and intramuscular administration [0056], [0057]. EP-3 650 044 A1 discloses limitations of claims 11, 12 and 16 immunogenic composition and inducing immune response ( see claim 15). EP-3 650 044 A1 discloses the subject matter of claims 1, 4, 5, 7, 8, 11, 12 and 16. EP-3 650 044 A1 do not teach CDAP and CRM 197.
Kapre teaches conjugation of bacterial polysaccharides to virus like particles see title, abstract, para 0006, 0007, 0011,0013, claims and example 1. Kapre teaches streptococcus pneumoniae (see para 0026 and claims 6, 7) coupling e.g. by reductive amination or cyanylation and CDAP (see para 0011, 0022, claim 5) and uses as vaccine ( para 0011-0013 and claims). Kapre teaches limitations of clam 10, carrier protein and CRM 197 ( see para 0017, 0019, 0024 ).
The above references do not explicitly recite non-viral protein nanoparticle and Qbeta VLP.
Steinmetz et al. teach non-viral protein nanoparticles ( see claims 13, 33, 49 and para 0012, 0081, 0082). Steinmetz et al. teach Q beta ( see figures, para 0012, 0013, 00162, 00163, 00174). Steinmetz et al. teach a sequence 100% identical to SEQ ID NO:1. See sequence alignment below:
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the teachings of the references to obtain the claimed invention. Because EP-3 650 044 A1 discloses the conjugation of bacterial capsular polysaccharides (CPS) to virus-like particles. And Kapre teaches conjugation of bacterial polysaccharides to virus like particles wherein the bacterial saccharide is from streptococcus pneumoniae coupling e.g. by reductive amination or cyanylation and CDAP. Steinmetz et al. teach non-viral protein nanoparticles such as Q beta. The combination of references teach the claimed invention. One of the ordinary of skill in the art would be motivated to use non-virus particles in the conjugate because non-virus particles produce antigenic molecules on the surface.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to combine known compositions thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
RESULT 5
BFG15128
ID BFG15128 standard; protein; 159 AA.
XX
AC BFG15128;
XX
DT 28-JUN-2018 (first entry)
XX
DE Qbeta-CH401 fusion protein.
XX
KW CH401 protein; Qbeta protein; brain tumor; breast tumor; cancer;
KW coat protein; colon tumor; cytostatic; drug delivery; fusion protein;
KW lung tumor; melanoma; melt processed degradable viral nanoparticle;
KW metastasis; nanotechnology; ovary tumor; therapeutic; virotherapy.
XX
OS Rattus sp.
OS Chimeric.
OS Synthetic.
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Protein 1..133
FT /note= "Qbeta coat protein"
FT Region 134..140
FT /note= "Linker"
FT Region 141..159
FT /note= "CH401 protein"
XX
CC PN WO2018085658-A1.
XX
CC PD 11-MAY-2018.
XX
CC PF 03-NOV-2017; 2017WO-US059935.
XX
PR 03-NOV-2016; 2016US-0417000P.
XX
CC PA (UCWR ) UNIV CASE WESTERN RESERVE.
XX
CC PI Steinmetz NF, Pokorski J;
XX
DR WPI; 2018-36346Q/35.
XX
CC PT New melt processed degradable viral nanoparticle construct useful for
CC PT delivering virus or virus-like particles to site, for treating cancer,
CC PT comprises degradable polymer matrix, and virus-like particles
CC PT encapsulated within matrix.
XX
CC PS Example 2; Page 66; 130pp; English.
XX
CC The present invention relates to a novel melt processed degradable viral
CC nanoparticle construct which is used for delivering a virus or a virus-
CC like particles to a site for treating cancer. The melt processed
CC degradable viral nanoparticle construct comprises a degradable polymer
CC matrix and virus-like particles encapsulated within the matrix. The
CC invention further relates to: (1) a melt processed agricultural construct
CC ; and (2) a method of treating cancer or tumor in a subject by
CC administering melt processed nanoparticle construct to the cancer or
CC tumor cells of the subject in situ. The melt processed degradable viral
CC nanoparticle construct is used for delivering virus or virus-like
CC particles to a site of interest, for treating metastatic cancer,
CC melanoma, brain cancer, breast cancer, colon cancer, lung cancer, and
CC ovarian cancer. The melt processed degradable viral nanoparticle
CC construct can be synthesized without using solvent and injected in a
CC minimally invasive manner and it maintains same or substantially similar
CC structural and biochemical characteristics of the virus or virus-like
CC particles before melt processing upon release from degradable polymer
CC matrix. The present sequence is a Qbeta-CH401 fusion protein which is
CC contained in a melt processed degradable viral nanoparticle construct
CC that is used for delivering a virus or a virus-like particles to a site
CC for treating cancer.
XX
SQ Sequence 159 AA;
Query Match 100.0%; Score 668; Length 159;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAKLETVTLGNIGKDGKQTLVLNPRGVNPTNGVASLSQAGAVPALEKRVTVSVSQPSRNR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAKLETVTLGNIGKDGKQTLVLNPRGVNPTNGVASLSQAGAVPALEKRVTVSVSQPSRNR 60
Qy 61 KNYKVQVKIQNPTACTANGSCDPSVTRQAYADVTFSFTQYSTDEERAFVRTELAALLASP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KNYKVQVKIQNPTACTANGSCDPSVTRQAYADVTFSFTQYSTDEERAFVRTELAALLASP 120
Qy 121 LLIDAIDQLNPAY 133
|||||||||||||
Db 121 LLIDAIDQLNPAY 133
Conclusion
10. No claims are allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHATOL S SHAHNAN SHAH whose telephone number is (571)272-0863. The examiner can normally be reached on Mon-Tue, Thurs-Fri 12pm-8pm.
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, Daniel E. Kolker can be reached on (571) 272 -0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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.
/KHATOL SHAHNAN -SHAH/
Examiner, Art Unit 1645
January 8, 2026
/JANA A HINES/Primary Examiner, Art Unit 1645