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 1-30 are pending.
Applicant’s election with traverse for examination of Group II (claims 17- 30, directed to a method of reducing the level of acidic species of an anti-IL-1R1 antibody, or antigen-binding portion thereof, in a clarified harvest from a cell culture, the method comprising harvesting the cell culture when the viability decreases to no less than about 50%, thereby reducing the level of acidic species of the anti-IL-1R1 antibody, or antigen-binding portion thereof, in the clarified harvest in the reply filed on 11/20/2025 in response of restriction requirement of 10/02/2025 is acknowledged. Traversal on the ground based on argument stating that “group I and II involve the same method step, and have the same effect of desirably affecting the levels of acidic species in a cell culture in the production of an anti-IL- 1R1 antibody, or antigen-binding portion” is considered but found unpersuasive because group I is a method of producing a composition whereas group II is method of reducing a compound ( acidic species) because indeed Group I and Group II are different methods. Group I method and Group II method belong to different class/ subclass and searching one class will not encompass another class; which would impose an undue burden on the Examiner. Therefore Claims 1-16 of group I will be withdrawn as they belong to non-elected group. Claims 17-30 are for examination. Restriction made final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/18/2025 and 07/22/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the IDS statement.
Claim Rejections 35 U.S.C 112(b) rejection
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.
Claim 17-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 17 is rejected because it recites the limitation “less than about 55%”. The limitations “less than” and “about” render the claims indefinite because the metes and bounds of the claim is indefinite.
Claim 18 is rejected because it recites the limitation “about 50%-100%, about 55%-100%, about 60%-100%, about 65%-100%, about 70%-100%, about 75%-100%, about 80%-100%, about 85%-100%, about 90%-100%, about 50%-70%, or about 55%-65%” indefiniteness arises because claim includes a broad range and a narrow range within the same claim (e.g., " about 50%-100%, about 55%-100%,"). A claim with both a broad and a narrow range (e.g., about 50%-100%, about 55%-100%) can be indefinite because it's unclear if the narrow part is required or just exemplary.
Claim 19 is rejected because it recites the limitation “no less than about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 99%”. The limitations “no less than ” and “about” render the claims indefinite because the metes and bounds of the claim is indefinite.
Claim also includes a broad range and a narrow range within the same claim (e.g., " about 55%, about 60%,---"). A claim with both a broad and a narrow range (e.g, about 55%, about 60%) can be indefinite because it's unclear if the narrow part is required or just exemplary
Claim 20 is rejected because it recites the limitation “about 50%, about 55%, about 60%, about 65%, or about 70%.”. indefiniteness arises as claim includes a broad range and a narrow range within the same claim (e.g., " about 50%, about 55%"). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim 21 is rejected because it recites the limitation “about 0.4 x 106 to about 0.8 x 106 cells /mL, about 0.4 x 106 to about 0.7 x 106 cells /mL, or about 0.4 x 106 to about 0.6 x 106 cells /mL.”. indefiniteness arises as the claim includes a broad range and a narrow range within the same claim (e.g., " about 0.4 x 106 to about 0.8 x 106 "). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim 22 is rejected because it recites the limitation “about 0.4 x 106 cells /mL, about 0.5 x 106 cells /mL, about 0.6 x 106 cells /mL, about 0.7 x 106 cells /mL, or about 0.8 x 106 cells /mL”. indefiniteness arises as claim includes a broad range and a narrow range within the same claim (e.g., " about 0.4 x 106 to about 0.5 x 106 "). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim 23 is rejected because it recites the limitation “ about 8 days to about 20 days--,no more than about 20 days”. The limitations “no more than ” and “about” render the claims indefinite because the metes and bounds of the claim is indefinite.
Claim also includes a broad range and a narrow range within the same claim (e.g., " about 8 days to about 20 days ).A claim with both a broad and a narrow range (e.g., about 8 days to about 20 days ) can be indefinite because it's unclear if the narrow part is required or just exemplary
Claim 24 is rejected because it recites the limitation “about 20 days, about 19 days, about 18 days, about 17 days, about 16 days, about 15 days, about 14 days, about 13 days, about 12 days, about 11 days, about 10 days, about 9 days, or about 8 days”. indefiniteness arises as claim includes a broad range and a narrow range within the same claim (e.g., " about 20 days, about 19 days "). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim 25 is rejected because it recites the limitation “about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 99%”. indefiniteness arises as claim includes a broad range and a narrow range within the same claim (e.g., " about 50%, about 55%"). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim 25 is rejected because it recites the limitation “at least about 50%, ---”. The limitations “at least” and “about” render the claims indefinite because the metes and bounds of the claim is indefinite.
Claim 26 is rejected because it recites the limitation “about 50%-100%, about 55%-100%, about 60%-100% about 65%-100%, about 70%-100%, about 75%-100%, about 80%-100%, about 85%-100%, about 90%-100%, about 50%-70%, or about 55%-65%”. indefiniteness arises as claim includes a broad range and a narrow range within the same claim (e.g., " about 50%-100%, about 55%-100%"). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim 27 is rejected because it recites the limitation “less than about 55%---”. The limitations “less than ” and “about” render the claims indefinite because the metes and bounds of the claim is indefinite.
Claim 27 is rejected because it recites the limitation “about 55%, about 54%, about 53%, about 52%, about 51%, about 50%, about 49%, about 48%, about 47%, about 46%, about 45%, about 44,%, about 43%, about 42%, about 41%, about 40%,about 39%, about 38%, about 37%, about 36%, about 35%, about 34%, about 33%, about 32%, about 31%, about 30% acidic species of the antibody; or wherein the clarified harvest comprises about 30-55%, about 31-55%, about 32-55%, about 33-55%, about 34-55%, about 35-55%, about 30-40%, about 31-40%, about 32-40%, about 33-40%, about 34-40%, about 35-40%, about 31-39%, about 31-38%, about 31-37%, about 31-36%, about 32-39%, about 32-38%, about 32-37%, about 32-36%, about 33-39%, about 33-38%, about 33-37%, about 33-36%, about 34-39%, about 34-38%, about 34-37%, or about 34-36% acidic species”. indefiniteness arises is when a claim includes a broad range and a narrow range within the same claim (e.g., " about 55%, about 54%"). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim 28 is rejected because it recites the limitation “about 1-5%, about 2-5%, about 2-4%, about 1- 4%, or about 1-5%, or about 1-6%, or about 1-7%, or about 1-8%, or about 1-9%, or about 1-10%, or about 1-11%, or about 1-12%, or about 1-13%, or about 1-14%, or about 1-15% basic species of the antibody; (b) wherein the clarified harvest comprises about 40-70%, about 40-65%, about 40-60%, about 40-55%, about 40-50%, about 55-75%, about 55-70%, about 60-70%, about 60-65%, or about 60-63%”. indefiniteness arises is when a claim includes a broad range and a narrow range within the same claim (e.g., " about 1-5%, about 2-5%"). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim 28 is rejected because it recites the limitation “less than about 15% basic species, and more than about 40% main species--”. The limitations “less than ” or “more than” and “about” render the claims indefinite because the metes and bounds of the claim is indefinite.
Claim 29 is rejected because it recites the limitation “about 40-80% isoform B, about 10-30% isoform A/B, and/or about 10-30% isoform A of the antibody;(b) wherein the clarified harvest comprises about 50-75% isoform B, about 15-25% isoform A/B, and/or about 10-25% isoform A of the antibody; or (c) wherein the clarified harvest comprises about 45-60% isoform B, about 20-30% isoform A/B, and/or about 15-30% isoform A”. indefiniteness arises as claim includes a broad range and a narrow range within the same claim (e.g., " about 40-80% isoform B, about 50-75% isoform B"). The claim may be considered indefinite if it is unclear whether the narrower range is merely exemplary or a required feature of the claim.
Claim Rejections, 35 U.S.C 112 1st Paragraph
The following is a quotation of the first paragraph of 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 17-30 are rejected under 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
It is noted that MPEP 2111.01 states that "[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow." In this case, in light of the specification, the examiner has broadly interpreted the claims by reciting “method of reducing the level of acidic species of an anti-IL-1R1 antibody, or antigen-binding portion thereof, in a clarified harvest from a cell culture, the method comprising harvesting the cell culture when the viability decreases to no less than about 50%, thereby reducing the level of acidic species of the anti-IL-1R1 antibody, or antigen-binding portion thereof, in the clarified harvest” wherein said antibody having any structure from any source or any fragment of SEQ ID NOs: 1-10 ( Claim 30) ( an amino acid sequence of SEQ ID NO can comprise several residues of said sequence) that when expressed in a cell culture reduces acidic species of said antibody having the viability decreases to no less than about 50%, thereby reducing the level of acidic species of the anti-IL-1R1 antibody.
Therefore in light of the specification, claims are broadly interpreted to comprise antibody having any structure from any source that when expressed in a cell culture reduces acidic species of said antibody having the viability decreases to no less than about 50%, thereby reducing the level of acidic species of the anti-IL-1R1 antibody.
The Court of Appeals for the Federal Circuit has recently held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lilly and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description (see Enzo paraphrased above).
There is no structure-function correlation with regard to the members of the genus of antibody having any structure from any source or any fragment of SEQ ID NOs: 1-10 ( Claim 30) ( an amino acid sequence of SEQ ID NO comprise several residues of said sequence) that when expressed in a cell culture reduces acidic species of said antibody having the viability decreases to no less than about 50%, thereby reducing the level of acidic species of the anti-IL-1R1 antibody. Therefore one of skill in the art would not recognize from the disclosure that applicants were in possession of the claimed invention.
The genus of antibody having any structure from any source that when expressed in a cell culture reduces acidic species of said antibody having the viability decreases to no less than about 50%, thereby reducing the level of acidic species of the anti-IL-1R1 antibody recited in the instant claims recited belong to broad class of antibody polypeptides specification does not teach. Specification only teach KPL-387 a Human IgG2 and variant thereof having structure comprising SEQ ID NO: 1-10 ( see specification para 0264). However the claims are directed to antibody having any structure from any source or any fragment of SEQ ID NOs: 1-10 ( Claim 30) including mutant, recombinant required in the claimed invention is an extremely large structurally and functionally variable genus.
Prior arts teach Human IgG2 antibodies comprise various structural variants and prone to structural modification to form acidic species see Wypych et al. JBC , 2008, 283(23), pp 16194-16205 and also Dada et al., Electrophoresis, 215, 36, pp-2695-2702.
An argument can be made that the recited genus of antibody polypeptides is adequately described by the disclosure of the structure in the specification at various examples and at examples 1-5 such as SEQ ID NO: 1-10. However, the art clearly teaches there is a practical limits to predict function of a polypeptide based structural homology:
A. Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that "Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, and page 105).
B. Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340,) also highlight the difficulties associated with "Prediction of protein function from protein sequence and structure": "To reason from sequence and structure to function is to step onto much shakier ground", closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein's role fundamentally (page 323, paragraph 1).
C. This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a beta -ketoacyl synthase into a malonyl decarboxylase and completely eliminates beta-ketoacyl synthase activity. The art also teaches that functionally similar molecules have different structures; Kisselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated above, no information beyond the characterization of a few species SEQ ID NO: 1-10 which when express in cell culture reduces the level of acidic species of an anti-IL-1R1 antibody, or antigen-binding portion thereof via viability decrease to no less than about 50%, thereby reducing the level of acidic species of the anti-IL-1R1 antibody, has been provided by the applicants’, which would indicate that they had the possession of the claimed genus of polypeptides. The claimed genera of antibodies polypeptides and the have widely variable structures and associated functions in the claims by the instant claims.
As it is discussed above, a minor changes in structure may result in changes affecting function, since, the specification provided no additional information (species/variant/mutant) correlating structure with function, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Furthermore, "Possession may not be shown by merely describing how to obtain possession of members of the claimed ,genus or how to identify their common structural features" (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895). A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the .gene does (function), rather what it is (structure), see University of California v. Eli Lilly & Co., 43 USPQ2d 1938, thus above claims lack adequate written description.
Applicants' are referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov
Conclusion
Claims 17-30 are rejected. No claim is allowed.
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examiner should be directed to Mohammad Meah whose telephone number is 571-272-
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supervisor, Robert Mondesi can be reached on 4089187584. The fax phone number
for the organization where this application or proceeding is assigned is 571-273-8300.
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/MOHAMMAD Y MEAH/Examiner, Art Unit 1652