DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status and Formal Matters
The response has amended claim 1 to provide (i) and (ii). However, the numbers are not underlined as required by 37 CFR 1.121. However to promote compact prosecution and customer service the instant response will be examined. However, future amendments that are non-compliant with 37 CFR 1.121 may not be entered or examined.
Priority
The instant application was filed 05/08/2025 and is a continuation of 17930742 , filed 09/09/2022 ,which is a Continuation of 17406765 , filed 08/19/2021 , which is a continuation of 17061891 , filed 10/02/2020 ,which is a continuation of 16295031 , filed 03/07/2019 which is a continuation of 15421808 , filed 02/01/2017 ,which is a divisional of 14342565 filed 10/28/2014, which is a National Stage entry of PCT/EP2011/065304 filed 9/5/2011.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/14/2025 is being considered by the examiner.
The listing of references in the specification 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.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7-15 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.
MPEP 2163 IB New or amended claims section II
With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."); and MPEP § 2163.04
Claim 7 was added by amendment on 8/14/2025. The response of 8/14/2025 merely asserts the amendments are supported throughout the specification. Review and searching revealed support for the numbers, but not the specific ranges. While tables 1 and 2 provide support for some of the numbers, it does not appear to provide support for the ranges or blaze marks to come to the ranges. Thus the claims appear to introduce new matter
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 1-20 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 has been amended to recite, “wherein the polypeptide comprises 19 repeating units derived from the C-terminal domain of Clostridium difficile (C. difficile) toxin A and 23 repeating units derived from the C-terminal domain of C. difficile toxin B;(ii) a second antigen.” The metes and bounds are unclear if this is and additional element or is encompassed by the recited SEQ ID NO of (i). Further it is unclear if “derived from” requires100% sequence identity, something less than complete identity, or some other way related to the repeating units. Thus one of skill in the art is not adequately apprised of what is inside or outside the scope of the claims.
Claim 7 has been amended to recite, “wherein the second C-terminal portion from C. difficile toxin B comprises amino acids 1988-2366 corresponding to SEQ ID NO: 8 and does not comprise amino acids 1834- 1967 corresponding to SEQ ID NO: 8.” The recitation of corresponding is not an art accepted term. The specification and claims do not define what is required of corresponding. The metes and bounds are unclear what “corresponding” requires. It is unclear if it require complete sequence identity, some percentage of sequence identity, an amino acid sequence or something else.
Claim 9 recites, “wherein the polypeptide comprises the first C-terminal portion from C. difficile toxin A comprises amino acids 2121-2686 corresponding to SEQ ID NO: 6.” The recitation of corresponding is not an art accepted term. The specification and claims do not define what is required of corresponding. The metes and bounds are unclear what “corresponding” requires. It is unclear if it require complete sequence identity, some percentage of sequence identity, an amino acid sequence or something else. Further the claim is confusing as the independent claim recites SEQ ID NO 8. Thus it is unclear how SEQ ID NO 6 is related to the SEQ ID No 8 of the independent claim. Further it is unclear how this further limits the claims.
Claim 10 recites, “wherein the polypeptide comprises the first C-terminal portion from C. difficile toxin A, comprising amino acids 2276-2710 corresponding to SEQ ID NO: 6.” The recitation of corresponding is not an art accepted term. The specification and claims do not define what is required of corresponding. The metes and bounds are unclear what “corresponding” requires. It is unclear if it require complete sequence identity, some percentage of sequence identity, an amino acid sequence or something else. Further the claim is confusing as the independent claim recites SEQ ID NO 8. Thus it is unclear how SEQ ID NO 6 is related to the SEQ ID No 8 of the independent claim. Further it is unclear how this further limits the claims.
Claim 11 recites, “wherein the polypeptide comprises the first C-terminal portion from C. difficile toxin A, comprising amino acids 2276-2686 corresponding to SEQ ID NO: 6.” The recitation of corresponding is not an art accepted term. The specification and claims do not define what is required of corresponding. The metes and bounds are unclear what “corresponding” requires. It is unclear if it require complete sequence identity, some percentage of sequence identity, an amino acid sequence or something else. Further the claim is confusing as the independent claim recites SEQ ID NO 8. Thus it is unclear how SEQ ID NO 6 is related to the SEQ ID No 8 of the independent claim. Further it is unclear how this further limits the claims.
Claim 12 recites, “wherein the polypeptide comprises the first C-terminal portion from C. difficile toxin A, does not comprise amino acids 2687-2710 corresponding to SEQ ID NO: 6.” The recitation of corresponding is not an art accepted term. The specification and claims do not define what is required of corresponding. The metes and bounds are unclear what “corresponding” requires. It is unclear if it require complete sequence identity, some percentage of sequence identity, an amino acid sequence or something else. Further the claim is confusing as the independent claim recites SEQ ID NO 8. Thus it is unclear how SEQ ID NO 6 is related to the SEQ ID No 8 of the independent claim. Further it is unclear how this further limits the claims.
Claim 13 has been amended to recite, “wherein the polypeptide comprises at least 19 repeating units derived from the C-terminal domain of C. difficile toxin A.” The recitation of “derived” is not an art accepted term. It is unclear if “derived from” requires100% sequence identity, something less than complete identity, or some other way related to the repeating units. Thus one of skill in the art is not adequately apprised of what is inside or outside the scope of the claims. Further it is unclear how this further limits the claims.
Claim 14 has been amended to recite, “wherein the polypeptide comprises fewer than 23 repeating units derived from the C-terminal domain of C. difficile toxin B.” The recitation of “derived” is not an art accepted term. It is unclear if “derived from” requires100% sequence identity, something less than complete identity, or some other way related to the repeating units. Thus one of skill in the art is not adequately apprised of what is inside or outside the scope of the claims. Further it is unclear how this further limits the claims.
Claim 15 recites, “wherein the composition is capable of inducing neutralizing antibodies against both C. difficile toxins A and B.” The recitation of “capable of inducing” suggests there are compositions not capable of inducing neutralizing antibodies against both C. difficile toxins A and B. The specification does not provide a definition or standard to differentiate capable from incapable of inducing neutralizing antibodies against both C. difficile toxins A and B. Further it is unclear how this further limits the claims.
Claim 16 has been amended to recite, “wherein the polypeptide comprises 19 repeating units derived from the C-terminal domain of Clostridium difficile (C. difficile) toxin A and 23 repeating units derived from the C-terminal domain of C. difficile toxin B;(ii) a second antigen.” The metes and bounds are unclear if this is and additional element or is encompassed by the recited SEQ ID NO of (i). Further it is unclear if “derived from” requires100% sequence identity, something less than complete identity, or some other way related to the repeating units. Thus one of skill in the art is not adequately apprised of what is inside or outside the scope of the claims.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claim(s) 1-3, 5-19 is/are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Telfer (WO2010017383).
With regards to claim 1, Telfer teaches, “009] In one aspect, the invention provides an attenuated microorganism expressing an immunogenic peptide that comprises an immunogenic portion of a C. difficile Toxin A C-terminal repeat region and/or a C. difficile Toxin B C-terminal repeat region. The microorganism is capable of presenting the C. difficile antigen(s) to the host immune system in a manner that generates an effective immune response. In certain embodiments, the attenuated microorganism is an attenuated Salmonella comprising an integrated gene expression cassette that directs the expression of the immunogenic peptide from an in vivo inducible promoter, such as the Salmonella ssaG promoter (ssaGp), ssrA promoter (ssrAp), or sseA promoter (sseAp), for example. The immunogenic peptide may be secreted from the microorganism via a secretion signal or tag, such as CIyA or a non-hemolytic derivative thereof.” Telfer teaches, “0092] The composition may comprise the microorganism as described, and a pharmaceutically acceptable carrier, for instance, a pharmaceutically acceptable vehicle, excipient and/or diluent. The pharmaceutically acceptable carrier can be any solvent, solid or encapsulating material in which the vaccine can be suspended or dissolved. The pharmaceutically acceptable carrier is non-toxic to the inoculated individual and compatible with the live, attenuated microorganism.” Telfer teaches SEQ ID NO 21 ( amino acids 759-1741) which comprises instant SEQ ID NO 2 and additional amino acids (second antigen)
With regards to claim 2, Telfer teaches the composition can contain glycoproteins (0094).
With regards to claim 3, Telfer teaches, “0092] The composition may comprise the microorganism as described, and a pharmaceutically acceptable carrier, for instance, a pharmaceutically acceptable vehicle, excipient and/or diluent. The pharmaceutically acceptable carrier can be any solvent, solid or encapsulating material in which the vaccine can be suspended or dissolved. The pharmaceutically acceptable carrier is non-toxic to the inoculated individual and compatible with the live, attenuated microorganism.”
With regards to claims 5-6, Telfer teaches,” [0095] In certain embodiments, the compositions further comprise at least one adjuvant or other substance useful for enhancing an immune response. For instance, the invention includes a composition comprising a live, attenuated Salmonella bacterium of the invention with a CpG oligodeoxynucleotide adjuvant. Adjuvants with a CpG motif are described, for instance, in US Patent Application 20060019239, which is herein incorporated by reference in its entirety.[0096] Other adjuvants that can be used in a vaccine composition with the attenuated microorganism of the invention, include, but are not limited to, aluminium salts (e.g., Alhydrogel) such as aluminium hydroxide, aluminum oxide and aluminium phosphate, oil-based adjuvants such as Freund's Complete Adjuvant and Freund's Incomplete Adjuvant, mycolate-based adjuvants (e.g., trehalose dimycolate), bacterial lipopolysaccharide (LPS), peptidoglycans (e.g., mureins, mucopeptides, or glycoproteins such as N-Opaca, muramyl dipeptide [MDP], or MDP analogs), proteoglycans (e.g., extracted from Klebsiella pneumoniae), streptococcal preparations (e.g., OK432), muramyldipeptides, Immune Stimulating Comlexes (the "Iscoms" as disclosed in EP 109 942, EP 180 564 and EP 231 039), saponins, DEAE-dextran, neutral oils (such as miglyol), vegetable oils (such as arachis oil), liposomes, polyols, the Ribi adjuvant system (see, for instance, GB-A-2 189 141 ), vitamin E, Carbopol or interleukins, particularly those that stimulate cell mediated immunity.”
Claim 7-15 are unclear in view of the recitation of corresponding language and referencing different SEQ ID NO. Thus the broadest reasonable interpretation is the claims are peptides and this encompassed by SEQ ID NO 2 or SEQ ID NO 4.
With regards to claim 7, Telfer teaches, “009] In one aspect, the invention provides an attenuated microorganism expressing an immunogenic peptide that comprises an immunogenic portion of a C. difficile Toxin A C-terminal repeat region and/or a C. difficile Toxin B C-terminal repeat region. The microorganism is capable of presenting the C. difficile antigen(s) to the host immune system in a manner that generates an effective immune response. In certain embodiments, the attenuated microorganism is an attenuated Salmonella comprising an integrated gene expression cassette that directs the expression of the immunogenic peptide from an in vivo inducible promoter, such as the Salmonella ssaG promoter (ssaGp), ssrA promoter (ssrAp), or sseA promoter (sseAp), for example. The immunogenic peptide may be secreted from the microorganism via a secretion signal or tag, such as CIyA or a non-hemolytic derivative thereof.” Telfer teaches, “0092] The composition may comprise the microorganism as described, and a pharmaceutically acceptable carrier, for instance, a pharmaceutically acceptable vehicle, excipient and/or diluent. The pharmaceutically acceptable carrier can be any solvent, solid or encapsulating material in which the vaccine can be suspended or dissolved. The pharmaceutically acceptable carrier is non-toxic to the inoculated individual and compatible with the live, attenuated microorganism.” Telfer teaches SEQ ID NO 21 ( amino acids 759-1741) which comprises instant SEQ ID NO 2 and additional amino acids (second antigen). Telfer teaches, “[0094] In one embodiment of the invention, the composition comprises one or more of the following carriers: disodium hydrogen phosphate, soya peptone, potassium dihydrogen phosphate, ammonium chloride, sodium chloride, magnesium sulphate, calcium chloride, sucrose, sterile saline and sterile water. In one embodiment of the invention, the composition comprises an attenuated Salmonella enteήca serovar (e.g., Typhi or Typhimurium) with deleted or inactivated SPI2 (e.g., ssaV) and aroC genes and one or more gene expression cassettes comprising a nucleic acid encoding a C. difficiles toxin A and/or toxin B C-terminal repeating unit under the control of an in vivo inducible promoter (e.g., ssaG promoter) and a carrier comprising, for instance, at least one of disodium hydrogen phosphate, soya peptone, potassium dihydrogen phosphate, ammonium chloride, sodium chloride, magnesium sulphate, calcium chloride, sucrose, sodium bicarbonate and sterile water.” Telfer teaches culturing in example 2. Thus Telfer teaches the introduction of a recombinant nucleic encoding the construct of claim 1 into a cell, culturing and combining with a pharmaceutically acceptable carrier.
With regards to claim 8, Telfer teaches the composition can contain glycoproteins (0094).
Claims 9-15 are indefinite for the reasons of record and thus appear to be anticipated by the teachings of Telfer.
With regards to claim 16, Telfer teaches, “009] In one aspect, the invention provides an attenuated microorganism expressing an immunogenic peptide that comprises an immunogenic portion of a C. difficile Toxin A C-terminal repeat region and/or a C. difficile Toxin B C-terminal repeat region. The microorganism is capable of presenting the C. difficile antigen(s) to the host immune system in a manner that generates an effective immune response. In certain embodiments, the attenuated microorganism is an attenuated Salmonella comprising an integrated gene expression cassette that directs the expression of the immunogenic peptide from an in vivo inducible promoter, such as the Salmonella ssaG promoter (ssaGp), ssrA promoter (ssrAp), or sseA promoter (sseAp), for example. The immunogenic peptide may be secreted from the microorganism via a secretion signal or tag, such as CIyA or a non-hemolytic derivative thereof.” Telfer teaches, “0092] The composition may comprise the microorganism as described, and a pharmaceutically acceptable carrier, for instance, a pharmaceutically acceptable vehicle, excipient and/or diluent. The pharmaceutically acceptable carrier can be any solvent, solid or encapsulating material in which the vaccine can be suspended or dissolved. The pharmaceutically acceptable carrier is non-toxic to the inoculated individual and compatible with the live, attenuated microorganism.” Telfer teaches SEQ ID NO 21 ( amino acids 759-1741) which comprises instant SEQ ID NO 2 and additional amino acids (second antigen). Telfer teaches, “0099] The compositions of the present invention can be administered via parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal and buccal routes. Alternatively, or concurrently, administration may be noninvasive by either the oral, inhalation, nasal, or pulmonary route.” Thus Telfer anticipates the claim.
With regards to claim 17 Telfer teaches, “0099] The compositions of the present invention can be administered via parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal and buccal routes. Alternatively, or concurrently, administration may be noninvasive by either the oral, inhalation, nasal, or pulmonary route.”
With regards to claim 18-19, Telfer teaches, “0096] Other adjuvants that can be used in a vaccine composition with the attenuated microorganism of the invention, include, but are not limited to, aluminium salts (e.g., Alhydrogel) such as aluminium hydroxide, aluminum oxide and aluminium phosphate, oil-based adjuvants such as Freund's Complete Adjuvant and Freund's Incomplete Adjuvant, mycolate-based adjuvants (e.g., trehalose dimycolate), bacterial lipopolysaccharide (LPS), peptidoglycans (e.g., mureins, mucopeptides, or glycoproteins such as N-Opaca, muramyl dipeptide [MDP], or MDP analogs), proteoglycans (e.g., extracted from Klebsiella pneumoniae), streptococcal preparations (e.g., OK432), muramyldipeptides, Immune Stimulating Comlexes (the "Iscoms" as disclosed in EP 109 942, EP 180 564 and EP 231 039), saponins, DEAE-dextran, neutral oils (such as miglyol), vegetable oils (such as arachis oil), liposomes, polyols, the Ribi adjuvant system (see, for instance, GB-A-2 189 141 ), vitamin E, Carbopol or interleukins, particularly those that stimulate cell mediated immunity.” Thus Telfer anticipates the claim.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 1-20 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Telfer (WO2010017383) and Vajdy (US 20100158943 ).
With regards to claim 1, Telfer teaches, “009] In one aspect, the invention provides an attenuated microorganism expressing an immunogenic peptide that comprises an immunogenic portion of a C. difficile Toxin A C-terminal repeat region and/or a C. difficile Toxin B C-terminal repeat region. The microorganism is capable of presenting the C. difficile antigen(s) to the host immune system in a manner that generates an effective immune response. In certain embodiments, the attenuated microorganism is an attenuated Salmonella comprising an integrated gene expression cassette that directs the expression of the immunogenic peptide from an in vivo inducible promoter, such as the Salmonella ssaG promoter (ssaGp), ssrA promoter (ssrAp), or sseA promoter (sseAp), for example. The immunogenic peptide may be secreted from the microorganism via a secretion signal or tag, such as CIyA or a non-hemolytic derivative thereof.” Telfer teaches, “0092] The composition may comprise the microorganism as described, and a pharmaceutically acceptable carrier, for instance, a pharmaceutically acceptable vehicle, excipient and/or diluent. The pharmaceutically acceptable carrier can be any solvent, solid or encapsulating material in which the vaccine can be suspended or dissolved. The pharmaceutically acceptable carrier is non-toxic to the inoculated individual and compatible with the live, attenuated microorganism.” Telfer teaches SEQ ID NO 21 ( amino acids 759-1741) which comprises instant SEQ ID NO 2 and additional amino acids (second antigen)
Telfer does not specifically teach the pharmaceutical composition comprises antibiotics.
However, Vadjy teaches propagation a virus or antigen expression in cells (0048, 0050). Vadjy teaches, “ 0054] Compositions of the invention may include detergent e.g. a polyoxyethylene sorbitan ester surfactant (known as `Tweens`), an octoxynol (such as octoxynol-9 (Triton X-100) or t-octylphenoxypolyethoxyethanol), a cetyl trimethyl ammonium bromide (`CTAB`), or sodium deoxycholate, particularly for a split or surface antigen vaccine. The detergent may be present only at trace amounts. Thus the vaccine may included less than 1 mg/ml of each of octoxynol-10, .alpha.-tocopheryl hydrogen succinate and polysorbate 80. Other residual components in trace amounts could be antibiotics (e.g. neomycin, kanamycin, polymyxin B).”
Therefore it would have been prima facie to one of ordinary skill in the art at the time the invention was made to allow for residual amounts of antibiotics to be present in the composition. The artisan would be motivated to allow for residual amounts of antibiotics to be present as it would be hard and/or cost ineffective to process the composition if produced in cells to completely eliminate antibiotics present in culturing steps. Thus the artisan would be motivated by time and money. The artisan would have a reasonable expectation of success as the artisan is merely using known methods to produce peptide compositions.
With regards to claim 2, Telfer teaches the composition can contain glycoproteins (0094).
With regards to claim 3, Telfer teaches, “0092] The composition may comprise the microorganism as described, and a pharmaceutically acceptable carrier, for instance, a pharmaceutically acceptable vehicle, excipient and/or diluent. The pharmaceutically acceptable carrier can be any solvent, solid or encapsulating material in which the vaccine can be suspended or dissolved. The pharmaceutically acceptable carrier is non-toxic to the inoculated individual and compatible with the live, attenuated microorganism.”
With regards to claims 5-6, Telfer teaches,” [0095] In certain embodiments, the compositions further comprise at least one adjuvant or other substance useful for enhancing an immune response. For instance, the invention includes a composition comprising a live, attenuated Salmonella bacterium of the invention with a CpG oligodeoxynucleotide adjuvant. Adjuvants with a CpG motif are described, for instance, in US Patent Application 20060019239, which is herein incorporated by reference in its entirety.[0096] Other adjuvants that can be used in a vaccine composition with the attenuated microorganism of the invention, include, but are not limited to, aluminium salts (e.g., Alhydrogel) such as aluminium hydroxide, aluminum oxide and aluminium phosphate, oil-based adjuvants such as Freund's Complete Adjuvant and Freund's Incomplete Adjuvant, mycolate-based adjuvants (e.g., trehalose dimycolate), bacterial lipopolysaccharide (LPS), peptidoglycans (e.g., mureins, mucopeptides, or glycoproteins such as N-Opaca, muramyl dipeptide [MDP], or MDP analogs), proteoglycans (e.g., extracted from Klebsiella pneumoniae), streptococcal preparations (e.g., OK432), muramyldipeptides, Immune Stimulating Comlexes (the "Iscoms" as disclosed in EP 109 942, EP 180 564 and EP 231 039), saponins, DEAE-dextran, neutral oils (such as miglyol), vegetable oils (such as arachis oil), liposomes, polyols, the Ribi adjuvant system (see, for instance, GB-A-2 189 141 ), vitamin E, Carbopol or interleukins, particularly those that stimulate cell mediated immunity.”
Claim 7-15 are unclear in view of the recitation of corresponding language and referencing different SEQ ID NO. Thus the broadest reasonable interpretation is the claims are peptides and this encompassed by SEQ ID NO 2 or SEQ ID NO 4.
With regards to claim 7, Telfer teaches, “009] In one aspect, the invention provides an attenuated microorganism expressing an immunogenic peptide that comprises an immunogenic portion of a C. difficile Toxin A C-terminal repeat region and/or a C. difficile Toxin B C-terminal repeat region. The microorganism is capable of presenting the C. difficile antigen(s) to the host immune system in a manner that generates an effective immune response. In certain embodiments, the attenuated microorganism is an attenuated Salmonella comprising an integrated gene expression cassette that directs the expression of the immunogenic peptide from an in vivo inducible promoter, such as the Salmonella ssaG promoter (ssaGp), ssrA promoter (ssrAp), or sseA promoter (sseAp), for example. The immunogenic peptide may be secreted from the microorganism via a secretion signal or tag, such as CIyA or a non-hemolytic derivative thereof.” Telfer teaches, “0092] The composition may comprise the microorganism as described, and a pharmaceutically acceptable carrier, for instance, a pharmaceutically acceptable vehicle, excipient and/or diluent. The pharmaceutically acceptable carrier can be any solvent, solid or encapsulating material in which the vaccine can be suspended or dissolved. The pharmaceutically acceptable carrier is non-toxic to the inoculated individual and compatible with the live, attenuated microorganism.” Telfer teaches SEQ ID NO 21 ( amino acids 759-1741) which comprises instant SEQ ID NO 2 and additional amino acids (second antigen). Telfer teaches, “[0094] In one embodiment of the invention, the composition comprises one or more of the following carriers: disodium hydrogen phosphate, soya peptone, potassium dihydrogen phosphate, ammonium chloride, sodium chloride, magnesium sulphate, calcium chloride, sucrose, sterile saline and sterile water. In one embodiment of the invention, the composition comprises an attenuated Salmonella enteήca serovar (e.g., Typhi or Typhimurium) with deleted or inactivated SPI2 (e.g., ssaV) and aroC genes and one or more gene expression cassettes comprising a nucleic acid encoding a C. difficiles toxin A and/or toxin B C-terminal repeating unit under the control of an in vivo inducible promoter (e.g., ssaG promoter) and a carrier comprising, for instance, at least one of disodium hydrogen phosphate, soya peptone, potassium dihydrogen phosphate, ammonium chloride, sodium chloride, magnesium sulphate, calcium chloride, sucrose, sodium bicarbonate and sterile water.” Telfer teaches culturing in example 2. Thus Telfer teaches the introduction of a recombinant nucleic encoding the construct of claim 1 into a cell, culturing and combining with a pharmaceutically acceptable carrier.
With regards to claim 8, Telfer teaches the composition can contain glycoproteins (0094).
Claims 9-15 are indefinite for the reasons of record and thus appear to be anticipated by the teachings of Telfer.
With regards to claim 16, Telfer teaches, “009] In one aspect, the invention provides an attenuated microorganism expressing an immunogenic peptide that comprises an immunogenic portion of a C. difficile Toxin A C-terminal repeat region and/or a C. difficile Toxin B C-terminal repeat region. The microorganism is capable of presenting the C. difficile antigen(s) to the host immune system in a manner that generates an effective immune response. In certain embodiments, the attenuated microorganism is an attenuated Salmonella comprising an integrated gene expression cassette that directs the expression of the immunogenic peptide from an in vivo inducible promoter, such as the Salmonella ssaG promoter (ssaGp), ssrA promoter (ssrAp), or sseA promoter (sseAp), for example. The immunogenic peptide may be secreted from the microorganism via a secretion signal or tag, such as CIyA or a non-hemolytic derivative thereof.” Telfer teaches, “0092] The composition may comprise the microorganism as described, and a pharmaceutically acceptable carrier, for instance, a pharmaceutically acceptable vehicle, excipient and/or diluent. The pharmaceutically acceptable carrier can be any solvent, solid or encapsulating material in which the vaccine can be suspended or dissolved. The pharmaceutically acceptable carrier is non-toxic to the inoculated individual and compatible with the live, attenuated microorganism.” Telfer teaches SEQ ID NO 21 ( amino acids 759-1741) which comprises instant SEQ ID NO 2 and additional amino acids (second antigen). Telfer teaches, “0099] The compositions of the present invention can be administered via parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal and buccal routes. Alternatively, or concurrently, administration may be noninvasive by either the oral, inhalation, nasal, or pulmonary route.” Thus Telfer anticipates the claim.
Telfer does not specifically teach administering as a multidose regimen.
However, Vadjy teaches, “[0006] It has also been proposed to administer vaccines to patients by both of these routes. For example, reference 58 discloses a two-dose regimen for influenza vaccination in which a patient receives a parenteral dose (typically intramuscularly) and a mucosal dose (typically intranasally). These two vaccines are preferably administered to a patient during a single visit to a physician. The inclusion of a mucosal dose in the two-dose regimen is said to enhance the protective immune response achieved by the vaccine, and in particular to enhance the IgA antibody response. Reference 2 discloses a three-dose regimen, with mice receiving two doses of an adjuvanted monovalent vaccine by subcutaneous injection, followed by an unadjuvanted booster by the intranasal route.”
Therefore it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the glycoprotein antigen is administered as part of a multidose format. The artisan would be motivated to challenge the subject with the glycoprotein antigen to increase or prolong the immune response to the glycoprotein antigen. The artisan would have a reasonable expectation of success as the artisan is merely using known dosing method to administer vaccines.
With regards to claim 17 Telfer teaches, “0099] The compositions of the present invention can be administered via parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal and buccal routes. Alternatively, or concurrently, administration may be noninvasive by either the oral, inhalation, nasal, or pulmonary route.”
With regards to claim 18-19, Telfer teaches, “0096] Other adjuvants that can be used in a vaccine composition with the attenuated microorganism of the invention, include, but are not limited to, aluminium salts (e.g., Alhydrogel) such as aluminium hydroxide, aluminum oxide and aluminium phosphate, oil-based adjuvants such as Freund's Complete Adjuvant and Freund's Incomplete Adjuvant, mycolate-based adjuvants (e.g., trehalose dimycolate), bacterial lipopolysaccharide (LPS), peptidoglycans (e.g., mureins, mucopeptides, or glycoproteins such as N-Opaca, muramyl dipeptide [MDP], or MDP analogs), proteoglycans (e.g., extracted from Klebsiella pneumoniae), streptococcal preparations (e.g., OK432), muramyldipeptides, Immune Stimulating Comlexes (the "Iscoms" as disclosed in EP 109 942, EP 180 564 and EP 231 039), saponins, DEAE-dextran, neutral oils (such as miglyol), vegetable oils (such as arachis oil), liposomes, polyols, the Ribi adjuvant system (see, for instance, GB-A-2 189 141 ), vitamin E, Carbopol or interleukins, particularly those that stimulate cell mediated immunity.” Thus Telfer anticipates the claim.
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 1-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 9598472. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
The claims of the instant application are drawn to A pharmaceutical composition polypeptides comprising:(i) a polypeptide comprising an amino acid sequence having at least 85%, more preferably at least 90%, even more preferably at least 95%, most preferred 99% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 2 or SEQ ID NO: 4,wherein the polypeptide comprises 19 repeating units derived from the C-terminal domain of Clostridium difficile (C. difficile) toxin A and 23 repeating units derived from the C-terminal domain of C. difficile toxin B;(ii) a second antigen. Other claims are drawn to producing and using the composition.
Application of 472 is in the priority chain of the instant application. The claims of 472 are drawn to A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier or excipient.
Thus it would be prima facie obvious to one of ordinary skill in art at the time the invention was made the claims are a species encompassed by the instant claims/ Thus the instant claims are at least an obvious variant. Dependent claims are rejected as they are coextensive in scope.
Claims 1-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10357557. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
The claims of the instant application are drawn to A pharmaceutical composition polypeptides comprising:(i) a polypeptide comprising an amino acid sequence having at least 85%, more preferably at least 90%, even more preferably at least 95%, most preferred 99% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 2 or SEQ ID NO: 4,wherein the polypeptide comprises 19 repeating units derived from the C-terminal domain of Clostridium difficile (C. difficile) toxin A and 23 repeating units derived from the C-terminal domain of C. difficile toxin B;(ii) a second antigen. Other claims are drawn to producing and using the composition.
Application of 557 is in the priority chain of the instant application. The claims of 557 are drawn to An immunogenic or vaccine composition comprising an isolated polypeptide having at least 85% sequence identity to the amino acid sequence set forth in SEQ ID NO: 4 and a pharmaceutically acceptable carrier or excipient, wherein the sequence identity is determined by Needleman-Wunsch global alignment..
Thus it would be prima facie obvious to one of ordinary skill in art at the time the invention was made the claims are a species encompassed by the instant claims/ Thus the instant claims are at least an obvious variant. Dependent claims are rejected as they are coextensive in scope.
Claims 1-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10821166. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
The claims of the instant application are drawn to A pharmaceutical composition polypeptides comprising:(i) a polypeptide comprising an amino acid sequence having at least 85%, more preferably at least 90%, even more preferably at least 95%, most preferred 99% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 2 or SEQ ID NO: 4,wherein the polypeptide comprises 19 repeating units derived from the C-terminal domain of Clostridium difficile (C. difficile) toxin A and 23 repeating units derived from the C-terminal domain of C. difficile toxin B;(ii) a second antigen. Other claims are drawn to producing and using the composition.
Application of 116 is in the priority chain of the instant application. The claims of 116 are drawn to A method for the prevention and/or treatment of a C. difficile associated disease (CDAD) comprising administering to a subject: a) an isolated polypeptide, or b) a pharmaceutical composition or immunogenic vaccine comprising the isolated polypeptide, wherein the polypeptide comprises an amino acid sequence having at least 85% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 4 and comprises 23 repeating units derived from the C-terminal domain of toxin B of C. difficile, wherein the sequence identity is determined by Needleman-Wunsch global alignment...
Thus it would be prima facie obvious to one of ordinary skill in art at the time the invention was made the claims are a species encompassed by the instant claims/ Thus the instant claims are at least an obvious variant. Dependent claims are rejected as they are coextensive in scope.
Claims 1-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11357844. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
The claims of the instant application are drawn to A pharmaceutical composition polypeptides comprising:(i) a polypeptide comprising an amino acid sequence having at least 85%, more preferably at least 90%, even more preferably at least 95%, most preferred 99% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 2 or SEQ ID NO: 4,wherein the polypeptide comprises 19 repeating units derived from the C-terminal domain of Clostridium difficile (C. difficile) toxin A and 23 repeating units derived from the C-terminal domain of C. difficile toxin B;(ii) a second antigen. Other claims are drawn to producing and using the composition.
Application of 844 is in the priority chain of the instant application. The claims of 844 are drawn A method for producing a recombinant polypeptide derived from Clostridium difficile toxins A and B, the method comprising i) introducing a recombinant nucleic acid encoding said polypeptide into a host cell, and ii) culturing the host cell under conditions that allow expression of said polypeptide, wherein the polypeptide comprises an amino acid sequence having at least 85% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 4, wherein the sequence identity is determined by Needleman-Wunsch global alignment.
Thus it would be prima facie obvious to one of ordinary skill in art at the time the invention was made the claims are a species encompassed by the instant claims/ Thus the instant claims are at least an obvious variant. Dependent claims are rejected as they are coextensive in scope.
Claims 1-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11478540. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
The claims of the instant application are drawn to A pharmaceutical composition polypeptides comprising:(i) a polypeptide comprising an amino acid sequence having at least 85%, more preferably at least 90%, even more preferably at least 95%, most preferred 99% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 2 or SEQ ID NO: 4,wherein the polypeptide comprises 19 repeating units derived from the C-terminal domain of Clostridium difficile (C. difficile) toxin A and 23 repeating units derived from the C-terminal domain of C. difficile toxin B;(ii) a second antigen. Other claims are drawn to producing and using the composition.
Application of 540 is in the priority chain of the instant application. The claims of 540 are drawn An isolated polypeptide comprising a first C-terminal portion from Clostridium difficile (C. difficile) toxin A and a second C-terminal portion from C. difficile toxin B, wherein the second C-terminal portion from C. difficile toxin B comprises amino acids 1988-2366 corresponding to SEQ ID NO: 8 and does not comprise amino acids 1834-1967 corresponding to SEQ ID NO: 8..
Thus it would be prima facie obvious to one of ordinary skill in art at the time the invention was made the claims are a species encompassed by the instant claims/ Thus the instant claims are at least an obvious variant.
Dependent claims are rejected as they are coextensive in scope.
Claims 1-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12324831. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
The claims of the instant application are drawn to A pharmaceutical composition polypeptides comprising:(i) a polypeptide comprising an amino acid sequence having at least 85%, more preferably at least 90%, even more preferably at least 95%, most preferred 99% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 2 or SEQ ID NO: 4,wherein the polypeptide comprises 19 repeating units derived from the C-terminal domain of Clostridium difficile (C. difficile) toxin A and 23 repeating units derived from the C-terminal domain of C. difficile toxin B;(ii) a second antigen. Other claims are drawn to producing and using the composition.
Application of 831 is in the priority chain of the instant application. The claims of 831 are drawn method for producing a recombinant polypeptide derived from Clostridium difficile (C. difficile) toxins A and B, the method comprising i) producing a recombinant nucleic acid encoding said polypeptide, ii) introducing a recombinant nucleic acid encoding said polypeptide into a host cell, and iii) culturing the host cell under conditions that allow expression of said polypeptide, wherein the polypeptide comprises a first C-terminal portion from C. difficile toxin A and a second C-terminal portion from C. difficile toxin B, and wherein the second C-terminal portion from C. difficile toxin B comprises amino acids 1988-2366 corresponding to SEQ ID NO: 8 and does not comprise amino acids 1834-1967 corresponding to SEQ ID NO: 8...
Thus it would be prima facie obvious to one of ordinary skill in art at the time the invention was made the claims are a species encompassed by the instant claims/ Thus the instant claims are at least an obvious variant.
Dependent claims are rejected as they are coextensive in scope.
Summary
No claims are allowed.
Conclusion
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
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