DETAILED ACTION
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
Claims 1-5 are pending and under examination in the instant office action.
Information Disclosure Statement
Applicants are kindly reminded of their duty to disclose pursuant to 37 C.F.R. 1.56 which encompasses the citation of references material to patentability of which Applicants are aware, such as references that may have been cited in the International Search Report of the parent applicant or in the specification.
Claim Interpretation
Regarding claim 1, “a modified colostrum protein vector having an amino acid sequence as shown in SEQ ID NO: 1” is interpreted as an open definition meaning “comprising the amino acid sequence of SEQ ID NO: 1”. The examiner also notes that “an antigenic fragment” as understood by an artisan need not be a peptide, but could also be a sugar or a lipid that stimulates the immune system. Additionally, the examiner notes that the adjective “antigenic” can be applied to anything, because “antigenic” is relative to the immune system of a subject; therefore, if the fragment is recognized as foreign by the immune system it is therefore antigenic. Regarding the limitation that the antigenic fragment is “linked to the modified colostrum protein vector”, the examiner refers to the 112(b) below.
Regarding claim 5, “said method comprising: applying a pharmaceutical composition containing the modified colostrum protein composition as claimed in claim 1 to a subject in need thereof” (emphasis is the Examiner’s). Although applying is not defined in the specification, the instant specification teaches mice fed yeast containing the modified colostrum protein composition [0026], [0040]. Applying is interpreted to encompass any and all methods of administering the protein composition including administering by application to a mucosal surface (e.g. feeding, intranasal) or any other method of administration (e.g. orally, parenterally, intravenously) and containing is interpreted as comprising.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5 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 1 recites the limitation “protein vector”. The claim is indefinite because “protein vector” is not a term defined by the art or the specification. It is unclear if the applicant is referring to a vector, which typically comprises a nucleic acid encoding a protein or if the claim is directed towards polypeptides comprising SEQ ID NO: 1, an amino acid sequence.
Dependent claims are rejected for failing to resolve the indefiniteness as described.
For the purposes of expedited prosecution, the claim will be interpreted as directed towards a modified colostrum protein composition comprising a modified colostrum protein comprising SEQ ID NO: 1 and an antigenic fragment linked to SEQ ID NO: 1.
Claims 2 and 3 recite the limitation "the amino acid sequence of the antigenic fragment" in line 2. There is insufficient antecedent basis for this limitation in the claims.
Claim 2 is indefinite for the recitation of “the amino acid sequence of the antigenic fragment is selected from partial amino acid sequence of pathogenic bacteria and/or viruses of diseases triggering mucosal immunity”. It is unclear what the metes and bounds of the claim are because it is unclear what structure of the amino acid sequence is required by “partial amino acid sequence”. Is one amino acid sufficient? Three? Additionally, the recitation of the function “triggering mucosal immunity” is unclear because it is uncertain how this functional limitation would be assessed. Does the partial amino acid sequence have to trigger the mucosal immunity? Does the pathogenic bacteria and/or virus have to trigger mucosal immunity? If so, how much triggering of mucosal immunity is required? Is the triggering by a composition comprising the partial amino acid sequence, bacteria, and/or virus, or must the triggering of mucosal immunity occur in response to a composition consisting of the partial amino acid sequence/bacteria/virus? This is unclear, and therefore the metes and bounds of the claim are indefinite. For the purposes of expedited prosecution, the claim will be interpreted as directed towards a composition wherein the antigenic fragment comprises an amino acid sequence of a protein from a pathogenic bacteria and/or virus.
Claim 3 is indefinite for the recitation of “the amino acid sequence of the antigenic fragment is selected from partial amino acid sequences of tumor markers”. It is unclear what the metes and bounds of the claim are because it is unclear what structure of the amino acid sequence is required by “partial amino acid sequence”. Is one amino acid sufficient? Three? The examiner notes that neither an antigenic fragment nor a tumor marker is required to be a protein. Thus, the metes and bounds of the claim are indefinite.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1 and 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 20170260256 A1 to Yu, Tse-Min et. al. published 14 September 2017 as evidenced by NCBI Reference Sequence NP_005082.1 “peptidoglycan recognition protein 1 precursor [Homo sapiens]” in view of WO2007011216 to Leenhouts et. al. published 25 January 2007.
Yu et. al. teaches a modified colostrum protein of SEQ ID NO: 1 (100% identical to instant SEQ ID NO: 1) which is generated by replacing Ile at position 33, Glu at position 101 and Arg at position 175 present in the amino acid of wild type colostrum protein of SEQ ID NO: 2. As evidenced by NCBI Reference Sequence NP_005082.1 “peptidoglycan recognition protein 1 precursor [Homo sapiens]”, SEQ ID NO: 2 is the human peptidoglycan recognition protein 1 (PGLYRP1). Yu et. al. teaches that SEQ ID NO: 1 is more stable compared with a wildtype colostrum protein and can increase the production of immunoglobulin IgA in pigs after being fed to pigs [0021], [0056]. Yu et. al. teaches that the colostrum protein interacts with the peptidoglycan layer in a bacterial cell wall [0032]. Yu et. al. teaches that the protein can be applied to animal feed to increase IgA response in a mammal or can be applied to the preparation of a pharmaceutical composition to be administered to an animal, wherein the pharmaceutical composition comprises a drug for disease prevention, a drug carrier, and a vaccine adjuvant [00035-0036]. Yu et. al. teaches that the protein can be applied to pharmaceutical compositions for preventing or treating avian influenza, human influenza, porcine reproductive and respiratory syndrome, or a disease which can cause a mucosal immune response [0037-0040]. Yu et. al. teaches that administration SEQ ID NO: 1 to pigs can increase the production of immunoglobulin IgA which neutralizes the PRRS virus with a tendency to penetrate mucosa tissue of pigs and to further activate the lymphatic system to produce IgG [0061].
Additionally, Yu et. al. teaches that the parent protein SEQ ID NO: 2 can be purified by binding to GEM [0055].
Yu et. al. does not explicitly teach a composition comprising SEQ ID NO: 1 and an antigenic fragment wherein the antigenic fragment is linked to the modified colostrum protein.
This deficiency is resolved by Leenhouts et. al.
Leenhouts et. al. teaches a bifunctional protein anchor of an antigen-loaded immunogenic carrier complex comprising at least one bifunctional polypeptide attached to an immunogenic carrier, said bifunctional polypeptide comprising a peptidoglycan binding domain through which the polypeptide is attached to said carrier, fused to an antigen binding domain to which at least one antigen of interest is bound (Abstract). Leenhouts et. al. teaches that the peptidoglycan binding domain allows for attachment to an immunogenic carrier such as a GEM (p. 3 lines 23-28). Leenhouts et. al. teaches that pre-treated peptidoglycan particles are derived from Gram-positive bacteria and contain bacterial components like peptidoglycan which have immunostimulatory properties (p. 2 lines 17-25). Leenhouts et. al. teaches “a PBD can be structurally defined in various manners. However, in all cases a PBD can be defined as a means for binding to the cell wall of a microorganism, wherein said means for binding is of peptidic nature. In one embodiment, the PBD is capable of binding to a Gram-positive bacterium or cell wall material derived thereof (e.g. a GEM particle). The binding capacity of a PBD can be readily determined in a binding assay comprising the steps of labeling the PBD with a reporter molecule, contacting the labeled PBD with a Gram-positive micro-organism to allow for binding of said means to said micro-organism; and determining the binding capacity of said PBD by detecting the absence or presence of reporter molecule associated with the micro-organism” (p. 9 lines 8-18). Leenhouts et. al. teaches that the carrier can be made with virtually any antigen, for example individual epitopes within a protective protein to develop peptide vaccines (p. 18 lines 2-21 (reads on antigen fragment). Leenhouts et. al. teaches that the bifunctional protein comprises an immunogenic carrier having adjuvant properties such as GEM (reads on adjuvant, claim 4) (p. 4 lines 10-20). Regarding claim 5, Leenhouts et. al. teaches “In one embodiment, the invention provides a pharmaceutical composition comprising an antigen-loaded immunogenic carrier complex according to the invention. For example, it provides an immunogenic composition comprising an antigen-loaded immunogenic carrier complex. An immunogenic composition is capable of inducing an immune response in an organism. In one embodiment, the immunogenic composition is a vaccine composition capable of inducing a protective immune response in an animal. The immunogenic composition, e.g. the vaccine, may be delivered to mucosal surfaces instead of being injected since mucosal surface vaccines are easier and safer to administer. A L. lactis derived immunogenic carrier complex may be used for mucosal vaccination since this bacterium is of intestinal origin and no adverse immune reactions are generally expected from L. lactis. Also provided is the use of an antigen binding immunogenic carrier complex according to the invention for the delivery of an (protective) antigen of interest to the immune system of a subject. The antigen binding immunogenic carrier complex comprises at least one bifunctional polypeptide attached to an immunogenic carrier, said polypeptide comprising a peptidoglycan binding domain (PBD) through which the polypeptide is attached to said carrier, fused to an antigen binding domain (ABD) capable of binding said antigen of interest […]”. Leenhouts additionally teaches that “especially mucosal immunisation as a means of inducing IgG and secretory IgA antibodies directed against specific pathogens of mucosal surfaces is considered an effective route of vaccination” (p. 1 lines 19-24).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to substitute the peptidoglycan binding domain of Leenhouts et. al. for SEQ ID NO: 1 of Yu et. al. in order to benefit from the known peptidoglycan binding function of PGLYRP1 and the immunostimulatory benefits as well as the increased stability of SEQ ID NO: 1 as taught by Yu et. al. in order to make a bifunctional peptide useful for vaccine compositions to target an antigen of interest as taught by Leenhouts et. al. This would have a reasonable expectation of success because Yu et. al. teaches that SEQ ID NO: 1 induces an IgA immune response and use of SEQ ID NO: 1 in a pharmaceutical composition comprising a vaccine adjuvant and Leenhouts et. al. teaches a vaccine carrier comprising a peptidoglycan binding protein linked to an antigenic fragment.
Regarding claim 4, modified Yu et. al. in view of Leenhouts teaches the composition comprising an immunogenic carrier with adjuvant properties such as the GEM particles (reads on the composition further comprising an adjuvant).
Regarding claim 5, Yu et. al. teaches a method of inducing an IgA response comprising administering SEQ ID NO: 1, but does not teach the method comprising administering SEQ ID NO: 1 linked to an antigenic fragment. Leenhouts et. al. teaches a method of inducing an immune response on mucosal surfaces to an antigen of interest comprising administering the bifunctional protein. See also the teachings of Yu et. al. and Leenhouts et. al. above. It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to administer the modified composition of Yu et. al. in view of Leenhouts et. al. to a subject in order to benefit from a method of increasing IgA production as taught be Yu et. al. and a method of inducing antigen-specific mucosal immunity as taught by Leenhouts et. al. This would have a reasonable expectation of success because an artisan would understand that increased mucosal immunity caused by a peptidoglycan recognition protein 1 would be expected to provide both a peptidoglycan binding function in a bifunctional protein and an artisan would further expect that a peptide capable of increasing IgA levels would increase the IgA response when part of a vaccine composition.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. 20170260256 A1 to Yu, Tse-Min et. al. published 14 September 2017 as evidenced by NCBI Reference Sequence NP_005082.1 “peptidoglycan recognition protein 1 precursor [Homo sapiens]” in view of WO2007011216 to Leenhouts et. al. published 25 January 2007 as applied to claim 1 above, and further in view of Charerntantanakul, Wasin, et al. "Immune responses and protection by vaccine and various vaccine adjuvant candidates to virulent porcine reproductive and respiratory syndrome virus." Veterinary immunology and immunopathology 109.1-2 (2006): 99-115 published 15 January 2006.
The teachings of Yu et. al. in view of Leenhouts et. al. in regards to claim 1 are in the 103 rejection above.
Modified Yu et. al. in view of Leenhouts et. al. does not explicitly teach the composition comprising SEQ ID NO: 1 linked to an antigenic fragment wherein the antigenic fragment comprises an amino acid sequence from a pathogenic bacteria and/or virus.
This deficiency is resolved by Charerntantanakul et. al.
Charerntantanakul et. al. teaches vaccination of pigs against porcine reproductive and respiratory syndrome virus (PRRSV) with a composition comprising modified-live virus and an adjuvant of mixed open reading frame 5 (ORF5) peptides derived from PRRSV isolates (Abstract, Table 1). The ORF5 adjuvant with live virus stimulated an antibody response (Fig. 1) and generated an increased T cell response compared to MLV alone (Fig. 3). Charerntantanakul et. al. teaches that only groups treated with MLV, with or without adjuvant, developed neutralizing antibodies after antigen challenge (Discussion ¶3). Charerntantanakul et. al. also teaches that pigs administered the ORF5 peptides alone failed to produce protective antibodies.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to used the ORF5 peptides of Charerntantanakul et. al. in modified bifunctional protein of Yu et. al. in view of Leenhouts et. al. in order to make an improved anti-PRRSV therapeutic composition as suggested by Yu et. al. and taught by Yu et. al. in view of Leenhouts et. al. This would have a reasonable expectation of success because Leenhouts et. al. teaches that virtually any antigen including subunit vaccine antigens are suitable for linking in the composition and that the bifunctional protein acts as an improved immunogenic carrier and Yu et. al. teaches improved IgA response to PRRSV in pigs. Therefore, an artisan would expect to make an improved protein adjuvant for the MLV vaccine of Charerntantanakul et. al. by combining the ORF5 peptides as the antigen of interest with the modified bifunctional protein of Yu et. al. in view of Leenhouts et. al.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. 20170260256 A1 to Yu, Tse-Min et. al. published 14 September 2017 as evidenced by NCBI Reference Sequence NP_005082.1 “peptidoglycan recognition protein 1 precursor [Homo sapiens]” in view of WO2007011216 to Leenhouts et. al. published 25 January 2007 as applied to claim 1 above, and further in view of Lynch, Kevin T., et al. "A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer." International Journal of Cancer 150.1 (2022): 164-173 published 3 September 2021.
The teachings of Yu et. al. in view of Leenhouts et. al. in regards to claim 1 are in the 103 rejection above.
Modified Yu et. al. in view of Leenhouts et. al. does not explicitly teach the composition comprising SEQ ID NO: 1 linked to an antigenic fragment wherein the antigenic fragment comprises an amino acid sequence from a tumor marker.
This deficiency is resolved by Lynch et. al.
Lynch et. al. teaches vaccination with CEA and HER2 peptides for the treatment of advanced colorectal cancer (CRC) using a composition comprising the peptides and GM_CSF emulsified in Montanide ISA-51 adjuvant for 3 weeks (Abstract, p. 166 section 2.3 “Peptides and Adjuvants”). Lynch et. al. teaches an immune response was detected and that 63% of HLA-A2 associated peptide and 100% of HLA-A3 associated peptides (p. 171, left column ¶1). Lynch et. al. teaches “Immune response to these peptides may also be increased by alternative vaccine adjuvants and use of toll-like receptor agonists” (p. 171 right column ¶1).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to us the CEA and HER2 peptides of Lynch et. al. as the target antigen in the modified bispecific peptide of Yu et. al. in view of Leenhouts et. al. above in order to benefit from an improved immunogenic carrier protein as taught by Leenhouts et. al. and the increased IgA immune response as taught by Yu et. al. in an anti-cancer vaccine as taught by Lynch et. al. This would have a reasonable expectation of success because Leenhouts et. al. teaches that virtually any antigen including subunit vaccine antigens are suitable for linking in the composition and that the bifunctional protein acts as an improved immunogenic carrier and Yu et. al. teaches improved IgA response. Therefore, an artisan would expect to make an improved protein adjuvant for the CEA and HER2 vaccine of Lynch et. al. by combining the CEA and HER2 peptides as the antigen of interest with the modified bifunctional protein of Yu et. al. in view of Leenhouts et. al.
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 and 4-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9834592 in view of WO2007011216 to Leenhouts et. al. published 25 January 2007.
Claim 1 of the ‘592 patent teaches a modified colostrum protein having an amino acid sequence shown in SEQ ID NO: 1 which is generated by replacing Ile at position 33, Glu at position 101 and Arg at position 175 present in the amino acid sequence of a wild type colostrum protein shown in SEQ ID NO: 2 respectively with Ala, Cys, and Cys. Claim 2 teaches a DNA sequence encoding SEQ ID NO: 1 having a base sequence shown in SEQ ID NO: 3. Claim 3 teaches a pharmaceutical composition comprising a drug carrier and a vaccine adjuvant and the modified colostrum protein according to claim 1.
The ’592 claims do not explicitly teach a composition comprising SEQ ID NO: 1 and an antigenic fragment wherein the antigenic fragment is linked to the modified colostrum protein.
This deficiency is resolved by Leenhouts et. al.
Leenhouts et. al. teaches a bifunctional protein anchor of an antigen-loaded immunogenic carrier complex comprising at least one bifunctional polypeptide attached to an immunogenic carrier, said bifunctional polypeptide comprising a peptidoglycan binding domain through which the polypeptide is attached to said carrier, fused to an antigen binding domain to which at least one antigen of interest is bound (Abstract). Leenhouts et. al. teaches that the peptidoglycan binding domain allows for attachment to an immunogenic carrier such as a GEM (p. 3 lines 23-28). Leenhouts et. al. teaches that pre-treated peptidoglycan particles are derived from Gram-positive bacteria and contain bacterial components like peptidoglycan which have immunostimulatory properties (p. 2 lines 17-25). Leenhouts et. al. teaches “a PBD can be structurally defined in various manners. However, in all cases a PBD can be defined as a means for binding to the cell wall of a microorganism, wherein said means for binding is of peptidic nature. In one embodiment, the PBD is capable of binding to a Gram-positive bacterium or cell wall material derived thereof (e.g. a GEM particle). The binding capacity of a PBD can be readily determined in a binding assay comprising the steps of labeling the PBD with a reporter molecule, contacting the labeled PBD with a Gram-positive micro-organism to allow for binding of said means to said micro-organism; and determining the binding capacity of said PBD by detecting the absence or presence of reporter molecule associated with the micro-organism” (p. 9 lines 8-18). Leenhouts et. al. teaches that the carrier can be made with virtually any antigen, for example individual epitopes within a protective protein to develop peptide vaccines (p. 18 lines 2-21 (reads on antigen fragment). Leenhouts et. al. teaches that the bifunctional protein comprises an immunogenic carrier having adjuvant properties such as GEM (reads on adjuvant, claim 4) (p. 4 lines 10-20). Regarding claim 5, Leenhouts et. al. teaches “In one embodiment, the invention provides a pharmaceutical composition comprising an antigen-loaded immunogenic carrier complex according to the invention. For example, it provides an immunogenic composition comprising an antigen-loaded immunogenic carrier complex. An immunogenic composition is capable of inducing an immune response in an organism. In one embodiment, the immunogenic composition is a vaccine composition capable of inducing a protective immune response in an animal. The immunogenic composition, e.g. the vaccine, may be delivered to mucosal surfaces instead of being injected since mucosal surface vaccines are easier and safer to administer. A L. lactis derived immunogenic carrier complex may be used for mucosal vaccination since this bacterium is of intestinal origin and no adverse immune reactions are generally expected from L. lactis. Also provided is the use of an antigen binding immunogenic carrier complex according to the invention for the delivery of an (protective) antigen of interest to the immune system of a subject. The antigen binding immunogenic carrier complex comprises at least one bifunctional polypeptide attached to an immunogenic carrier, said polypeptide comprising a peptidoglycan binding domain (PBD) through which the polypeptide is attached to said carrier, fused to an antigen binding domain (ABD) capable of binding said antigen of interest […]”. Leenhouts additionally teaches that “especially mucosal immunisation as a means of inducing IgG and secretory IgA antibodies directed against specific pathogens of mucosal surfaces is considered an effective route of vaccination” (p. 1 lines 19-24).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to substitute the peptidoglycan binding domain of Leenhouts et. al. for SEQ ID NO: 1 of ‘593 in order to benefit from the known peptidoglycan binding function of PGLYRP1 and the immunostimulatory benefits as well as the increased stability of SEQ ID NO: 1 as taught by ‘593 in order to make a bifunctional peptide useful for vaccine compositions to target an antigen of interest as taught by Leenhouts et. al. This would have a reasonable expectation of success because Yu et. al. teaches that SEQ ID NO: 1 induces an IgA immune response and use of SEQ ID NO: 1 in a pharmaceutical composition comprising a vaccine adjuvant and Leenhouts et. al. teaches a vaccine carrier comprising a peptidoglycan binding protein linked to an antigenic fragment.
Regarding claim 4, modified ‘593 in view of Leenhouts teaches the composition comprising an immunogenic carrier with adjuvant properties such as the GEM particles (reads on the composition further comprising an adjuvant).
Regarding claim 5, ‘593 does not teach a method of inducing an IgA response comprising administering SEQ ID NO: 1. However, MPEP 804.II.B.1 states “ In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02”. The specification was consulted to determine the use of SEQ ID NO: 1 and teaches that SEQ ID NO: 1 can be used to enhance IgA production (Col. 2 lines 23-29) and in particular can be mixed in feed for pigs to increase IgA production and prevent the infection in pigs with pathogens (Col. 2 lines 55-62; Col. 3 line 59-Col. 4 line 4).
Leenhouts et. al. teaches a method of inducing an immune response on mucosal surfaces to an antigen of interest comprising administering the bifunctional protein. See also the teachings of ‘592 and Leenhouts et. al. above. It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to administer the modified composition of ‘592 in view of Leenhouts et. al. to a subject in order to benefit from a method of increasing IgA production as taught by ‘592 and a method of inducing antigen-specific mucosal immunity as taught by Leenhouts et. al. This would have a reasonable expectation of success because an artisan would understand that increased mucosal immunity caused by a peptidoglycan recognition protein 1 would be expected to provide both a peptidoglycan binding function in a bifunctional protein and an artisan would further expect that a peptide capable of increasing IgA levels would increase the IgA response when part of a vaccine composition.
Claim 2 is rejected under on the ground of on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9834592 in view of WO2007011216 to Leenhouts et. al. published 25 January 2007 as applied to claim 1 above, and further in view of Charerntantanakul, Wasin, et al. "Immune responses and protection by vaccine and various vaccine adjuvant candidates to virulent porcine reproductive and respiratory syndrome virus." Veterinary immunology and immunopathology 109.1-2 (2006): 99-115 published 15 January 2006.
The teachings of ‘592 in view of Leenhouts et. al. in regards to claim 1 are in the 103 rejection above.
Modified ‘592 in view of Leenhouts et. al. does not explicitly teach the composition comprising SEQ ID NO: 1 linked to an antigenic fragment wherein the antigenic fragment comprises an amino acid sequence from a pathogenic bacteria and/or virus.
This deficiency is resolved by Charerntantanakul et. al.
Charerntantanakul et. al. teaches vaccination of pigs against porcine reproductive and respiratory syndrome virus (PRRSV) with a composition comprising modified-live virus and an adjuvant of mixed open reading frame 5 (ORF5) peptides derived from PRRSV isolates (Abstract, Table 1). The ORF5 adjuvant with live virus stimulated an antibody response (Fig. 1) and generated an increased T cell response compared to MLV alone (Fig. 3). Charerntantanakul et. al. teaches that only groups treated with MLV, with or without adjuvant, developed neutralizing antibodies after antigen challenge (Discussion ¶3). Charerntantanakul et. al. also teaches that pigs administered the ORF5 peptides alone failed to produce protective antibodies.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to use the ORF5 peptides of Charerntantanakul et. al. in modified bifunctional protein of ‘592 in view of Leenhouts et. al. in order to make an improved anti-PRRSV therapeutic composition as taught by Charerntantanakul et. al. and taught and to reduce pathogens in pigs as taught by ‘592 in view of Leenhouts et. al. This would have a reasonable expectation of success because Leenhouts et. al. teaches that virtually any antigen including subunit vaccine antigens are suitable for linking in the composition and that the bifunctional protein acts as an improved immunogenic carrier and ‘592 teaches improved IgA response to PRRSV in pigs. Therefore, an artisan would expect to make an improved protein adjuvant for the MLV vaccine of Charerntantanakul et. al. by combining the ORF5 peptides as the antigen of interest with the modified bifunctional protein of ‘592 in view of Leenhouts et. al.
Claim 3 is rejected under on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9834592 in view of WO2007011216 to Leenhouts et. al. published 25 January 2007 as applied to claim 1 above, and further in view of Lynch, Kevin T., et al. "A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer." International Journal of Cancer 150.1 (2022): 164-173.
The teachings of ‘592 in view of Leenhouts et. al. in regards to claim 1 are in the 103 rejection above.
Modified ‘592 in view of Leenhouts et. al. does not explicitly teach the composition comprising SEQ ID NO: 1 linked to an antigenic fragment wherein the antigenic fragment comprises an amino acid sequence from a tumor marker.
This deficiency is resolved by Lynch et. al.
Lynch et. al. teaches vaccination with CEA and HER2 peptides for the treatment of advanced colorectal cancer (CRC) using a composition comprising the peptides and GM_CSF emulsified in Montanide ISA-51 adjuvant for 3 weeks (Abstract, p. 166 section 2.3 “Peptides and Adjuvants”). Lynch et. al. teaches an immune response was detected and that 63% of HLA-A2 associated peptide and 100% of HLA-A3 associated peptides (p. 171, left column ¶1). Lynch et. al. teaches “Immune response to these peptides may also be increased by alternative vaccine adjuvants and use of toll-like receptor agonists” (p. 171 right column ¶1).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to us the CEA and HER2 peptides of Lynch et. al. as the target antigen in the modified bispecific peptide of ‘592 in view of Leenhouts et. al. above in order to benefit from an improved immunogenic carrier protein as taught by Leenhouts et. al. and the increased IgA immune response as taught by ‘592 in an anti-cancer vaccine as taught by Lynch et. al. This would have a reasonable expectation of success because Leenhouts et. al. teaches that virtually any antigen including subunit vaccine antigens are suitable for linking in the composition and that the bifunctional protein acts as an improved immunogenic carrier and ‘592 teaches improved IgA response. Therefore, an artisan would expect to make an improved protein adjuvant for the CEA and HER2 vaccine of Lynch et. al. by combining the CEA and HER2 peptides as the antigen of interest with the modified bifunctional protein of ‘592 in view of Leenhouts et. al.
Conclusion
No claims are allowed.
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/KATHLEEN CUNNINGCHEN/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678