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 .
The preliminary amendment filed 11/8/2024 is acknowledged. Claims 1, 3-17 are amended. New claim 18 is added. Claims 1-18 are pending and are currently under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification on at least pages 33-60 are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-18 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to compositions comprising: a) an A. baumannii strain deficient in lipopolysaccharide (LPS) characterized by the partial or complete inactivation of one or various cellular nucleic acid molecules that encode endogenous LPS biosynthesis genes; wherein the A.baumannii strain deficient in lipopolysaccharide (LPS) is characterized by the partial or complete inactivation of the genes selected from the list consisting of lpxA, lpxB, lpxC, lpxD, lpxK, lpxL and/or lpxM; and wherein the A.baumannii strain deficient in lipopolysaccharide (LPS) expresses one or more heterologous antigens or proteins with targeted location at the Outer Membrane; and/or b) an outer membrane vesicle (OMV) derived from an A. baumannii strain deficient in lipopolysaccharide (LPS) as defined in paragraph a) above; wherein the one or more heterologous antigens with targeted location at the outer membrane are characterized by comprising: I) at the N-terminus of the one or more heterologous antigens, a signal sequence derived from an outer membrane protein (OMP) which is processed by A.baumannii to direct the location of the expressed protein to the external membrane of A. baumannii; II) OMP transmembrane domains typical of integral OMP proteins or bacterial lipoproteins which allow insertion of the expressed protein at the external membrane of A. baumannii; and III) immunogenic domains; and wherein the strain is modified to express the one or more heterologous antigens with targeted location at the outer membrane by insertion of an expression construct comprising at least one or more transcription promoter sequences, one or more ORFs (Open Reading Frames) encoding the one or more heterologous antigens, and one or more transcription termination sequences at a locus in the A. baumannii chromosome that can incorporate an insert by recombination, selected from the list consisting of: cysl, trpE, lpxA, lpxC, lpxD, lpxB, lpxK, lpxL, lpxM, and/or the Tn5/Tn7 sites. Various dependent claims require signal sequences that are capable of promoting the location of the expressed protein to the outer membrane as well as various sequences (with only partial sequence identity) that are capable of producing immunization when the cell is administered to a subject.
The claims thus encompass a vast variety of genetic modifications to inactivate LPS synthesis while maintaining cellular growth and structural integrity along with recombinant production of any number of heterologous antigens that can be targeted to the outer membrane in the correct 3d conformation to produce protective immunity when the cells are administered to a subject of any species.
The specification discloses eleven specific constructs with insertions at specific points using various heterologous antigens. There is no guidance on which signal sequences, insertion sites, promoters or heterologous antigens other than these are capable of creating cells with the required functions.
The claims are thus drawn to a large genus of variants with no correlation provided between the structure and the required function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that
"applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
With the exception of the constructs disclosed in the specification, the skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
As taught in basic immunology texts, an epitope or antigenic determinant interacts with its corresponding antibody based on the three-dimensional structure of both molecules and the fit between them (Cruse et al., Illustrated Dict. of Immunology, 2nd ed., CRC Press, 2003, page 46). These epitopes can be conformational (or discontinuous) epitopes which are formed from separate regions in the primary sequence that are brought together by proper protein folding. Antibodies which bind to conformational epitopes will only bind to proteins folded into their proper native state (Cruse et al., page 166). There are also linear epitopes, which are regions of six amino acids in the primary sequence of a protein. These are generally not found on the surface of a folded protein and are only available to antibodies upon denaturation of a protein (Cruse et al., page 382). Since the claims involve methods which require induction of immunity, it seems that the antibodies must bind a protein that is in the proper folded state and thus to a conformational epitope. Since a conformational epitope is only found in a properly folded protein and can contain discontinuous portions of the protein, there is no way that one could determine whether a given polypeptide would bind to the antibody unless this were empirically tested. Any change (including deletions and substitutions), anywhere along the polypeptide is likely to alter the three-dimensional structure and folding of the protein, thus altering the antibody-antigen interaction. This is further supported by other authors such as McGuinness et al. (Mol. Microbiol., 7:505-514, 1993), Moudallal et al. (EMBO Journal, 1:1005-1010, 1982), and Abaza et al. (J. Prot. Chem., 11:433-444, 1992) who have shown that amino acid deletions, even outside an epitope will alter protein conformation and change antibody-antigen binding.
Therefore, only the constructs disclosed in the specification, but not the full breadth of the claims, meet the written description provision of 35 USC 112, first paragraph.
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 1-18 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 pre-AIA the applicant regards as the invention.
The claims appear to have grammatical and idiomatic errors (possibly from translation issues) that generally make the claims confusing. Different terms appear to be used interchangeably even though the words are not the same. For example, claim 1 refers to “heterologous antigens or proteins” but later the claims use these interchangeably. An additional example is the use of “outer membrane” and “external membrane”. Applicant also refers to OMP proteins, which does not make sense since OMP is an outer membrane protein, meaning applicant is now referring to an outer membrane protein protein.
Claim 1 is indefinite because it contains two improperly claimed Markush groups. The use of “and/or” makes the members of the group unclear.
Claim 1 is indefinite because, while it allows for expression of “one or more heterologous antigens or proteins” in part “a)”, it then goes on to require “the one or more heterologous antigens”. This precludes the use of proteins even though the claim allows for proteins.
The term “typical” in claim l is a relative term which renders the claim indefinite. The term “typical” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 2 is rendered indefinite by the phrases “these identical sequences” and “promote the location”. The term “identical” means the same. A sequence with 90% sequence identity to another sequence is not identical to that sequence. Additionally, the term “promote” does not make grammatical sense the way it is used in the claim.
Claim 4 is indefinite for several reasons. First, it is not clear how a protein (or proteins) can be “at least derived” from something. Additionally, the use of “and/or” makes the members of the Markush group unclear.
Claim 5 is indefinite for several reasons. First, it is not clear how a protein (or proteins) can be “at least derived” from something. Additionally, the use of “or” makes the members of the Markush group unclear. Further, the term “promote” does not make grammatical sense the way it is used in the claim.
Claim 6 is indefinite for several reasons. First, it is not clear how a protein (or proteins) can be “at least derived” from something. Additionally, the use of “or” makes the members of the Markush group unclear. Further, the term “promote” does not make grammatical sense the way it is used in the claim.
Claim 7 is indefinite for several reasons. First, it is not clear how a protein (or proteins) can be “at least derived” from something. Additionally, the use of “or” makes the members of the Markush group unclear. Further, the term “promote” does not make grammatical sense the way it is used in the claim.
Claim 8 is indefinite for several reasons. First, it is not clear how a protein (or proteins) can be “at least derived” from something. Additionally, the use of “or” makes the members of the Markush group unclear. Further, the term “promote” does not make grammatical sense the way it is used in the claim.
Claim 9 is indefinite for several reasons. First, it is not clear how a protein (or proteins) can be “at least derived” from something. Additionally, the use of “or” makes the members of the Markush group unclear.
Claim 10 is indefinite because a product cannot comprise an action (expression).
Claim 11 is indefinite because the Markush group lacks a conjunction.
Claim 15 is indefinite because the use of “and/or” makes the members of the Markush group unclear.
Claim 16 is indefinite because the way applicant uses the term “strains” does not make sense. A strain is a particular variant or subtype of a species. It seems unlikely that one could develop and place into a composition 10,000,000,000,000 different strains of a species. It is more likely that applicant intended for the vaccine to comprise this number of cells.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian J Gangle whose telephone number is (571)272-1181. The examiner can normally be reached M-F, 9-6:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN GANGLE/ Primary Examiner, Art Unit 1645
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