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 .
DETAILED ACTION
Claims 1-8 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 of Internation Application No. PCT/JP2022/036877 filed September 30, 2022, which claims the benefit of priority to Foreign Application No. JP2021-162273 filed September 30, 2021.
Certified copies of foreign priority applications have been received as required by 37 CFR 1.55. The priority date has been established as September 30, 2021.
Information Disclosure Statement
The Information Disclosure Statements filed on 10/18/2024 and 01/16/2026 have been considered and entered by examiner.
Drawings
The drawings are objected to because the legends for Figs. 6A, 6B, 6C, 7, 8A, 8B and 21 are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification (at least including sequences in paragraphs of [0013], [0046], [0050], [0054], [0057], [0058], [0059], [0060], [0061], [0157], [0161], [0164], [0181]) are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
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.
Specific deficiency - Sequences appearing in the drawings (e.g. Figs. 10, 11, 12, 17, and 18) are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, 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.
In addition, this application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that sequence GVYYFQGS (which appears in claim 5 and also in the specification) is not in XML. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claim 3-5 are objected to because of the following informalities: Sequences appearing in the claims are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like). Appropriate correction is required.
Claim 6 is objected to because of the following informalities: “an IgG antibody in a …” at line 4 should be “or an IgG antibody in a …” for clarity. Appropriate correction is required.
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 1-6 and 8 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.
The phrase “an impairment or disease attributed to liver inflammation” in claim 1 renders the claim indefinite. The phrase lacks clarity. The terms “impairment” and “disease” are themselves relative terms, and the phrase “attributed to liver inflammation” does not provide an objective criterion for determining which conditions are included. As a result, it is not possible for the skilled person to clearly identify the boundaries of the claim or to determine which disease are intended to be covered. The scope of the claims is therefore unclear. Incorporating the limitation of claim 7 would overcome the rejection.
Similarly, the phrase “an impairment or disease attributed to liver inflammation” in claim 8 renders the claim indefinite.
Claim 3 (a) recites “an antibody including: a heavy chain variable region containing an amino acid sequence of a heavy chain CDR1, an amino acid sequence of a heavy chain CDR2, and an amino acid sequence of a heavy chain CDR3, the heavy chain variable region containing an amino acid sequence set forth in SEQ ID NO: 7” which is ambiguous. It is noted that SEQ ID NO: 7 itself comprises HCDRs 1-3. It is unclear whether “an amino acid sequence of a heavy chain CDR1, an amino acid sequence of a heavy chain CDR2, and an amino acid sequence of a heavy chain CDR3” are the CDRS of SEQ ID NO: 7 or they are different set of CDRs. In addition, claim 3 (a) recites “and a light chain variable region containing an amino acid sequence of a light chain CDR1, an amino acid sequence of a light chain CDR2, and an amino acid sequence of a light chain CDR3, the light chain variable region containing an amino acid sequence set forth in SEQ ID NO: 8” which is ambiguous. It is noted that SEQ ID NO: 8 itself comprises LCDRs 1-3. It is unclear whether “an amino acid sequence of a light chain CDR1, an amino acid sequence of a light chain CDR2, and an amino acid sequence of a light chain CDR3” are the CDRS of SEQ ID NO: 8 or they are different set of CDRs. Similarly, the limitations of claim 3(b), 3(c), and 3(d) are ambiguous.
Claims 2, and 4-6 are also rejected because these claims depend on claim 1.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
Claims 1 is drawn to a pharmaceutical composition, a food composition, or a feed composition comprising a monoclonal antibody that binds to enteric bacteria or an antigen-binding fragment thereof, wherein the pharmaceutical composition, the food composition, or the feed composition is used for preventing or treating an impairment or disease attributed to liver inflammation. Given Broadest Reasonable Interpretation (BRI), the claim encompasses: 1) a broad genus of antibodies (and antigen-binding fragments thereof), which can bind a broad genus of antigens of a broad genus of enteric bacteria; 2) a broad genus of diseases attributed to liver inflammation. In the examples of the present application, therapeutic effect has only been demonstrated for the specific “W27 IgA antibody” (Example 1). No effect has been shown for other antibodies. Thus, the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed".
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been evaluated in view of that guidance. In the instant case, the claim encompasses a huge genus of antibodies to a broad genus of antigens. The specification only discloses one specific antibody (W27 IgA), which can bind specific epitopes (binding to the amino acid sequence RQEEHIELIAS in E. coli SHMT protein and the amino acid sequence VLDMMKLEKPE in C. difficile iPGM protein), for treating cholestasis liver impairment (Example 1). By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope (Almagro & Fransson, Frontiers in Bioscience 2008; 13: 1619-33 (see Section 3) "Antibody Structure and the Antigen Binding Site" and Figure I). Even a single point mutation in HCDR1 region could lead to antibody lose its binding activity (Ni et al., The Protein Journal, 43, pp. 683-696, July 2024, see Abstract). Thus, the specific antibody disclosed by the specification would not tell structure of other antibodies which have the same binding specificity and activity as that of W27 IgA.
Regarding “binds to enteric bacteria”, given BRI, “binds to enteric bacteria” would encompass antibodies to a huge genus of structurally different antigens from different enteric bacteria. As evidenced by the specification, enteric bacteria would at least include: bacteria belonging to the genus:
Prevotella Bacteroides, Megamonas, Bifidobacterium, Faecalibacterium, Coprococcus, Ruminococcus, Blautia, Eubacterium, Roseburia, Lactobacillus, Clostridium, Escherichia, Staphylococcus, Enterococcus, Pseudomonas, Enterorhabdus, and Fusobacterium.
For example, the claim would encompass all antibodies that can bind to any antigen from any of the bacteria above. Given the diversity of immunoglobulin sequences, this would encompass an essentially unlimited numbers of different antibody sequences. The specification discloses only one specific antibody (W27 IgA), which can bind specific epitopes/antigens (binding to the amino acid sequence RQEEHIELIAS in E. coli SHMT protein and the amino acid sequence VLDMMKLEKPE in C. difficile iPGM protein), for treating cholestasis liver impairment (Example 1). The specification does not teach any other antibody (or antigen-binding fragment thereof) which can bind to enteric bacteria and can prevent or treat an impairment or disease attributed to liver inflammation. As set forth above, W27 IgA does not teach other antibodies which can bind to the same epitope/antigen as W27 IGA, or antibodies which can bind to other antigens of enteric bacteria. Given the well-known high level of polymorphism of immunoglobulins/antibodies, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention, except the antibodies with the same CDR combination as W27 IgA.
In addition, the claim identify the antibodies by function only, where the function is to:
bind to enteric bacteria;
prevent or treat an impairment or disease attributed to liver inflammation;
bind to Clostridium difficile.
The specification and prior art have not established the relationship between the claimed functions and the structure of the antibody. One of ordinary skilled in the art would not be able to readily recognize/visualize an antibody with required properties, except the antibodies with the same HCDRs 1-3 and LCDRs 1-3 of W27 IgA. Taken together, applicant has not provided sufficient evidence to show that the inventors possess the claimed invention.
Claims 2, 6, and 7 also encompass a broadly claimed antibodies and compositions. Claim 8 is drawn to a method, but encompasses the same broadly claimed antibodies and compositions as claim 1. The specification lacks the written description support for claim1. Thus, logically, the specification lacks written description support for the method of using composition of claim 1.
Claims 3 and 4 recite specific sequences of CDRs. However, claim 3(e) and claim 4(e) recites “an antibody containing, with respect to a reference antibody including a heavy chain variable region containing an amino acid sequence set forth in SEQ ID NO: 37 and a light chain variable region containing an amino acid sequence set forth in SEQ ID NO: 38, at least one amino acid mutation in at least one region selected from heavy chains CDR1 to 3, light chains CDR1 to 3, and a light chain FR1, and binding to the amino acid sequence RQEEHIELIAS in E. coli SHMT protein and the amino acid sequence VLDMMKLEKPE in C. difficile iPGM protein”. By reciting “containing … at least one amino acid mutation”, these claims would encompass antibodies comprising sequences completely different from SEQ ID NO: 37 or SEQ ID NO: 38. As set forth above, the specification does not provide support for the broadly claimed antibodies.
Regarding claim 5, it is noted that there are at least 6 neutral polar amino acids, 2 acidic polar amino acids, and 16 non-polar/neutral polar amino acids. Accordingly claim 5 encompass 8 variants of HCDR1, 64 variants of HCDR2, 16 variants of LCDR1. Thus, just considering CDR combinations alone, claim 5 encompasses 8192 (8x64x16) different HCDRs 1-3 and LCDRs 1-3 combinations. As set forth above, the specification does not provide support for the broadly claimed antibodies.
Although Applicants may argue that it is possible to screen for antibodies with claimed properties/functions, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. "As we held in Lilly, "[a]n adequate written description of a DNA ... 'requires a precise definition, such as by structure, formula, chemical name, or physical properties,' not a mere wish or plan for obtaining the claimed chemical invention." 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171 ). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions." Knowledge of screening methods provides no information about the structure of any future antibodies or antibody fragments yet to be discovered that may function as claimed.
Taken together, the instant specification has not provided a sufficient description showing the necessary functional characteristics coupled with a known or disclosed correlation between functions and the structure. Thus, the specification is not sufficient to show the applicant was in possession of the genus of antibodies, and antibody fragments broadly encompassed for the claimed method.
Claim 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
a method for treating an impairment or disease attributed to liver inflammation, the method comprising administering a monoclonal antibody that binds to enteric bacteria to a subject in need of treatment of an impairment or disease attributed to liver inflammation, wherein the monoclonal antibody comprising: a heavy chain variable region comprising: a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 31;a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 32; and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and a light chain variable region comprising: a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 34; a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 35; and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 36, and wherein the impairment or disease attributed to liver inflammation is chronic hepatitis, liver fibrosis, liver cirrhosis, liver inflammation following liver transplantation, autoimmune hepatitis, or intrahepatic lithiasis,
does not reasonably provide enablement for:
a method for preventing or treating an impairment or disease attributed to liver inflammation, the method comprising administering a monoclonal antibody that binds to enteric bacteria to a subject in need of prevention or treatment of an impairment or disease attributed to liver inflammation.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with the claim. This is a SCOPE OF ENABLEMENT rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir.,1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547, the court recited eight factors to consider when assessing whether or not a disclosure would require undue experimentation. These factors are:
1) the quantity of experimentation necessary, 2) the amount of direction or guidance provided, 3) the presence or absence of working examples, 4) the nature of the invention 5) the state of the art, 6) the relative skill of those in the art, 7) the predictability of the art and 8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108,427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
Nature of invention and breadth of the claims:
The claims are drawn to a method for preventing or treating an impairment or disease attributed to liver inflammation, the method comprising administering a monoclonal antibody that binds to enteric bacteria to a subject in need of prevention or treatment of an impairment or disease attributed to liver inflammation.
As set forth above, given Broadest Reasonable Interpretation (BRI), the claim encompasses: 1) a broad genus of antibodies (and antigen-binding fragments thereof), which can bind a broad genus of antigens of a broad genus of enteric bacteria; 2) a broad genus of diseases attributed to liver inflammation.
Relative skill in the art:
The relative skill of those in the art is high with an MD or a PhD.
Level of unpredictability in the art and State of the prior art:
By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope (Almagro & Fransson, Frontiers in Bioscience 2008; 13: 1619-33 (see Section 3) "Antibody Structure and the Antigen Binding Site" and Figure I). Even a single point mutation in HCDR1 region could lead to antibody lose its binding activity (Ni et al., The Protein Journal, 43, pp. 683-696, July 2024, see Abstract). Thus, the specific antibody disclosed by the specification would not tell structure of other antibodies which have the same binding specificity and therapeutic activity as that of W27 IgA. Different antibodies to different antigens and/or different bacteria may have different therapeutic activity to a liver disease.
Direction or guidance and working examples:
The specification only discloses one specific antibody (W27 IgA), which can bind specific epitopes (binding to the amino acid sequence RQEEHIELIAS in E. coli SHMT protein and the amino acid sequence VLDMMKLEKPE in C. difficile iPGM protein), for treating cholestasis liver impairment (Example 1). However, the working example does not support the scope of the claims, which encompass unlimited antibodies with different CDR combinations from W27 IgA and a broad genus of impairments or diseases attributed to liver inflammation
The quantity of experimentation needed:
The factors outlined in In Re Wands' mentioned above apply here, and in particular as per the MPEP 2164.01 (a): "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." It is very clear that one could not make/use this very broad invention that has no working examples in this unpredictable art without undue experimentation. Genetech Inc vs Nova Nordisk 42 USPQ 2d 1001 "A patent is not a hunting license. It is not a reward for search but compensation for its successful conclusion and patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Given the numerous unspecified antibodies or antibody fragments and impairments/diseases encompassed by claim 8, the lack of specific guidance and the insufficient working examples, undue experimentation would be required of one of skilled in the art to produce the invention commensurate with the scope of the method as claimed.
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 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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 6, and 7 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Shinkura (Shinkura, US 2016/0039944 A1, Publication Date: 02/11/2016, cited in IDS of 10/18/2024).
It is noted that claim 1 is formulated as a product claim directed to a composition. The limitation “is used for preventing or treating an impatient or disease attributed to liver inflammation” is an intended use rather than adding physical or structural elements. Similarly, the limitation of claim 7 is also an intended use. Thus, these limitations carry no patentable weight.
Shinkura teaches monoclonal IgA antibody binding to serine hydroxy-methyltransferase (claim 1).
Shinkura teaches the monoclonal antibody: W27, which comprises a heavy chain variable of SEQ ID NO: 2 and a light chain variable of SEQ ID NO: 7 (Table 4, claim 3).
Shinkura teaches a pharmaceutical composition comprising the antibody (claim 14).
As shown below, SEQ ID NO: 2 comprises HCDRs 1-3 of instant SEQ ID NOs: 31-32-33; and SEQ ID NO: 7 comprises LCDRs 1-3 of instant SEQ ID NOs: 34-35-36:
US-14-773-923-2
Query Match 85.0%; Score 137.7; Length 124;
Best Local Similarity 40.3%;
Matches 29; Conservative 0; Mismatches 0; Indels 43; Gaps 2;
Qy 1 DYYIH--------------RIDPENDETTYAPKFQ------------------------- 21
||||| ||||||||||||||||
Db 40 DYYIHWVRQRTEQGLEWIGRIDPENDETTYAPKFQGKATMTADTSSNTAYLQLTSLTSED 99
Qy 22 ----YCARSTVL 29
||||||||
Db 100 TAVYYCARSTVL 111
US-14-773-923-7
Query Match 82.6%; Score 117.3; Length 143;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RASQSIVHTNG---------------KLLIYKV--------------------------- 18
||||||||||| |||||||
Db 33 RASQSIVHTNGNTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFILKISRV 92
Qy 19 -----GVYYCFQGS 27
|||||||||
Db 93 EAEDLGVYYCFQGS 106
W27 of Shinkura has the same HCDRs 1-3 and LCDRs 1-3 of W27G2. W27G2 has the same heavy and light variable regions of W27 (see [0420] of the instant publication US 2025/0051426 A1). As evidenced by instant publication, W27G2 has a heavy and a light variable regions of SEQ ID NO: 37 and SEQ ID NO: 38, respectively (page 18 and 19). As show in Example 4 of instant publication, W27 such as binding to E. coli SHMT and Clostridium difficile (see [0430] of the instant publication US 2025/0051426 A1).
Taken together, W27 of Shinkura reads on the antibody of instant claims 1, 2, 3(d), 4(d).
Regarding claim 6. W27 is an IgA antibody. And an IgA antibody can either be in a multimeric form or a monomeric form.
Shinkura teaches that W27 binds to various bacteria, including Escherichia coli (DH5a strain), Escherichia coli ( a cloned strain from mouse intestinal bacteria), Staphylococcus aureus, Enterococcus faecalis, Pseudomonas fulva, Lactobacillus murinus, Enterorhabdus mucosicola, Lactobacillus casei, Coprococcus eutactus, Blautia coccoides, Megamonas hypermegale, Eubacterium rectale, and Bifidobacterium
bifidum. As evidenced by the instant publication US 2025/0051426 A1, these bacteria are enteric bacteria (see [0143]-[0161]).
Shinkura teaches a pharmaceutical composition comprising the antibody (claim 14).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Czaja (Czaja et al., Hepatology, Vol. 19, No. 5, 1994, Publication Year: 1994, cited in IDS of 10/18/2024).
Czaja teaches that administration of a monoclonal anti-lipopolysaccharide (LPS) antibody (E5) reduced liver injury in rat subjected to acute toxic hepatotoxin exposure (Abstract).
Czaja teaches that in galactosamine-induced liver injury, E5 treatment reduced serum AST level by 43% at 36 hours and by 60% at 48 hours (page 1283, col. 2, para. 1; Fig. 1).
Czaja teaches the reductions were accompanied by less histological evidence of necrosis and inflammation (Fig. 2).
Although Czaja does not explicitly teach that E5 binds to enteric bacteria of the subject, Czaja teaches that LPS is a component of the cell wall of gram-negative bacteria. It would be obvious to an ordinary skilled in the art that E5 would bind to gram-negative bacteria such as E.coli (also enteric bacterium).
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 1-4, 6, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9,765,151 B2 (herein after Pat. 151) in view of Shinkura (Shinkura, US 2016/0039944 A1, Publication Date: 02/11/2016, cited in IDS of 10/18/2024). It is noted that Pat. 151 and Shinkura correspond to the same US Application: 14/773,923. Thus, they share the same disclosure including sequences.
It is noted that the instant claim 1 is formulated as a product claim directed to a composition. The limitation “is used for preventing or treating an impatient or disease attributed to liver inflammation” is an intended use rather than adding physical or structural elements. Similarly, the limitation of claim 7 is also an intended use. Thus, these limitations carry no patentable weight.
The claims of Pat. 151 teach a monoclonal antibody comprises a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 2, and/or a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 7 (claim 2). As set forth in 102 rejection, W27, which comprises a heavy chain variable of SEQ ID NO: 2 and a light chain variable of SEQ ID NO: 7 (Table 4).
The claims of Pat. 151 teach the monoclonal antibody is an IgA antibody (claim 6).
The claims of Pat. 151 teach a pharmaceutical composition comprising the monoclonal antibody (claim 12).
Thus, the reference patent claims are drawn to antibodies and pharmaceutical compositions related to the instant claims. However, it is noted that the reference patent claims do not explicitly disclose that the antibody binds to enteric bacteria, such as Clostridium difficile. The deficiencies are addressed by the Shinkura, as provided by the teachings specified in the 102 section.
The reference patent and Shinkura are considered to be analogous to the present invention as they are drawn in the overlapping antibodies and pharmaceutical compositions. Thus, it would have been obvious to one of ordinary skill in the art that the antibody taught by the claims of Pat. 151 would bind enteric bacteria, such as Clostridium difficile.
Claims 1-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 18/574, 919 (hereinafter Appl. 919).
It is noted that the instant claim 1 is formulated as a product claim directed to a composition. The limitation “is used for preventing or treating an impatient or disease attributed to liver inflammation” is an intended use rather than adding physical or structural elements. Similarly, the limitation of claim 7 is also an intended use. Thus, these limitations carry no patentable weight.
The claims of Appl. 919 teach a composition for inhibiting a growth of Clostridium difficile in a living body, the composition comprising a monoclonal antibody binding to a Clostridium difficile bacterial body or an antigen-binding fragment thereof (claim 1). Thus, claim 1 of Appl. 919 anticipates the instant claims 1, 2, and 7.
Regarding instantly claim 3, claim 4 of Appl. 919 teach d) an antibody comprising: a heavy chain variable region comprising an amino acid sequence of a heavy chain CDR1, an amino acid sequence of a heavy chain CDR2, and an amino acid sequence of a heavy chain CDR3, the heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 37; and a light chain variable region comprising an amino acid sequence of a light chain CDR1, an amino acid sequence of a light chain CDR2, and an amino acid sequence of a light chain CDR3, the light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 38 (claim 4). As evidenced by the Specification of Appl. 919, SEQ ID NOs: 37 and 38 of Appl. 919 are the same as SEQ ID NOs: 37 and 38 of the instant application, which are heavy and light chain variable domains of W27G2 (see page 32 of the Specification filed 09/06/2024).
Regarding instantly claim 4, claim 9 of Appl. 919 teach wherein the monoclonal antibody binding to a Clostridium difficile bacterial body is, as a reference antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 37, and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 38, an antibody comprising at least one amino acid mutation in at least one region selected from heavy chains CDR1 to 3, light chains CDR1 to 3, and a light chain FR1, and binding to the amino acid sequence RQEEHIELIAS in E. coli SHMT protein and the amino acid sequence VLDMMKLEKPE in C. difficile iPGM protein (claim 9).
Regarding instantly claim 5, claim 10 of Appl. 919 teach wherein the monoclonal antibody binding to a Clostridium difficile bacterial body is an antibody comprising: a heavy chain variable region comprising: a heavy chain CDR1 comprising an amino acid sequence of X1YYIH; a heavy chain CDR2 comprising an amino acid sequence of RIDPENX2X3TTYAPKFQ; and a heavy chain CDR3 comprising an amino acid sequence of YCARSTVL; and a light chain variable region comprising: a light chain CDR1 comprising an amino acid sequence of RX4SQSIVHTNG; a light chain CDR2 comprising an amino acid sequence of KLLIYKV; and a light chain CDR3 comprising an amino acid sequence of GVYYFQGS, in which a light chain FR1 contains an amino acid sequence of TPLSLPVSLGDQA or an amino acid sequence of SPASX5SVSLGDRX6, X1, X2, and X3 are each independently a neutral polar amino acid or an acidic polar amino acid, X4 is a non-polar amino acid or a neutral polar amino acid, and X5 and X6 are each independently a non-polar amino acid.
Regarding claim 6, W27G2 is an IgA antibody (see [0104] on page 43 of the Specification filed 09/06/2024). And an IgA antibody can either be in a multimeric form or a monomeric form.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to overlapping antibodies and pharmaceutical compositions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/574, 930 (hereinafter Appl. 930).
It is noted that the instant claim 1 is formulated as a product claim directed to a composition. The limitation “is used for preventing or treating an impatient or disease attributed to liver inflammation” is an intended use rather than adding physical or structural elements. Similarly, the limitation of claim 7 is also an intended use. Thus, these limitations carry no patentable weight.
The claims of Appl. 930 teach an antibody or an antigen-binding fragment thereof that binds to a Clostridium difficile bacterial body, which is: …; or d) as a reference antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 37, and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 38, the antibody or the antigen-binding fragment thereof comprising at least one amino acid mutation in at least one region selected from heavy chains CDR1 to 3, light chains CDR1 to 3, and a light chain FR1, and binding to the amino acid sequence RQEEHIELIAS in E. coli SHMT protein and the amino acid sequence VLDMMKLEKPE in C. difficile iPGM protein (claim 1).
As evidenced by the Specification of Appl. 930, SEQ ID NOs: 37 and 38 of Appl. 930 are the same as SEQ ID NOs: 37 and 38 of the instant application, which are heavy and light chain variable domains of W27G2 (see page 34 of the Specification filed 08/29/2024).
The claims of Appl. 930 teach a pharmaceutical composition comprising the antibody of claim 1 (claim 12).
Taken together, the claims of Appl. 930 teach the instant claims 1-3, and 7.
Regarding claim 6, W27G2 is an IgA antibody (see [0085] on page 46 of the Specification filed 08/29/2024). And an IgA antibody can either be in a multimeric form or a monomeric form.
Regarding instantly claim 4, claim 2 of Appl. 930 teach the antibody or the antigen-binding fragment thereof according to claim 1, wherein the antibody or the antigen-binding fragment thereof includes: a heavy chain variable region comprising: a heavy chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 1; a heavy chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 2; and a heavy chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 3; and a light chain variable region comprising:a light chain CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 4; a light chain CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 5; and a light chain CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 6;…. As evidenced by the Specification of 08/29/2024 (see page 25)), SEQ ID NOs: 1-6 of Appl. 930 are the same SEQ ID NOs: 1-6 of the instant application.
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Regarding instantly claim 5, claim 6 of Appl. 930 teach wherein the antibody is an antibody comprising: a heavy chain variable region comprising: a heavy chain CDR1 comprising an amino acid sequence of X1YYIH; a heavy chain CDR2 comprising an amino acid sequence of RIDPENX2X3TTYAPKFQ; and a heavy chain CDR3 comprising an amino acid sequence of YCARSTVL; and a light chain variable region comprising: a light chain CDR1 comprising an amino acid sequence of RX4SQSIVHTNG; a light chain CDR2 comprising an amino acid sequence of KLLIYKV; and a light chain CDR3 comprising an amino acid sequence of GVYYFQGS, in which a light chain FR1 contains an amino acid sequence of TPLSLPVSLGDQA or an amino acid sequence of SPASX5SVSLGDRX6, X1, X2, and X3 are each independently a neutral polar amino acid or an acidic polar amino acid, X4 is a non-polar amino acid or a neutral polar amino acid, and X5 and X6 are each independently a non-polar amino acid, excluding an antibody in which X1 is aspartic acid, X2 is aspartic acid, X3 is glutamic acid, X4 is alanine, and a light chain FR1 contains the sequence TPLSLPVSLGDQA.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to overlapping antibodies and pharmaceutical compositions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 6, and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 19/483,527 (hereinafter Appl. 527).
It is noted that the instant claim 1 is formulated as a product claim directed to a composition. The limitation “is used for preventing or treating an impatient or disease attributed to liver inflammation” is an intended use rather than adding physical or structural elements. Similarly, the limitation of claim 7 is also an intended use. Thus, these limitations carry no patentable weight.
The claims of Appl. 527 teach an antibody or an antigen-binding fragment of the antibody, comprising: a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 of a heavy chain variable region represented by SEQ ID NO: 3; and a light chain CDR1, a light chain CDR2, and a light chain CDR3 of a light chain variable region represented by SEQ ID NO: 4, or comprising: a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 of a heavy chain variable region represented by SEQ ID NO: 13; and a light chain CDR1, a light chain CDR2, and a light chain CDR3 of a light chain variable region represented by SEQ ID NO: 14, the antibody or the antigen-binding fragment that binds to bacterial cells of Clostridioides difficile (C. difficile) and inhibits growth of Clostridioides difficile (claim 1).
The claims of Appl. 527 teach a composition comprising the antibody or the antigen-binding fragment according to claim 1 (claim 7).
Taken together, the composition of Appl. 527 reads on the compositions of instant claims 1, 2 and 7. Regarding claim 6, as evidenced by the Specification of Appl. 527, SNK0005 has the heavy and light chain variable domains of SEQ ID NOs: 13 and 14, respectively ([0039]). And SNK0005 is an IgA antibody ([0042]). And an IgA antibody can either be in a multimeric form or a monomeric form.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to overlapping antibodies and pharmaceutical compositions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHENG LU/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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