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 .
Election/Restrictions
Applicant’s election without traverse of Group I claims 1-12 and the species of antibody with glycosylation at an N-Glycosylation site to an antibody light chain affinity ligand, GalT1and ST6 and full-length antibody in the reply filed on 2/26/2026 is acknowledged. Note that upon further consideration, that the species requirement of enzymes GalT1 and ST6 or galactosyltransferase and sialyltransferase is withdrawn.
Claims 1-2, 5 and 11-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/10/2021.
Claims 3-4 and 6-10 are under consideration in the instant Office Action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement filed 5/16/2023 fails to fully comply with 37 CFR 1.98(a)(2, which requires a legible copy of each foreign patents document and non-patent literature publication or that portion which causes it to be listed; and all other information or that portion which caused it to be listed. It has been places in the application file, but the citations have therefore, been lined through and have not been considered.
It is noted that the NPL reference numbered # 115, 168, 171, 188, 232, 234, 250, and 255 are all duplicate citations and therefore, not required and lined through.
Claim Rejections - 35 USC § 112
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 3-4 and 6-10 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.
In one of the embodiments of independent claim 3, call for a “…partial enzymatic modification…”. It is unclear what is meant by partial enzymatic modification. How does one determine what is a partial enzymatic modification. Is it glycosylated or not? MPEP § 2173.02 (II) states that one of the purposes of examination under 35 USC § 112, second paragraph is to determine whether the claim apprises one of ordinary skill in the art of its scope and, therefore, serves the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent. See, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). See also In re Larsen, No. 01-1092 (Fed. Cir. May 9, 2001) (unpublished). If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. See Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993). In this case, others are not fairly apprised of the scope of the claimed sequences for the claimed CDRs and heavy chains of the claimed antibodies and thus not fairly warned as to what constitutes infringement.
Since all dependent claims 4 and 6-10 all depend from independent claim 3 and do not resolve the indefinite issue, they also suffer from indefiniteness.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 3-4 and 6-9 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. Written Description
Claims 3-4 and 6-9 are directed to a method for the enzymatic production of a glycosylation modified antibody comprising applying a solution comprising an antibody with a glycosylation at an N-glycosylation to an antibody light chain affinity ligand bound to a solid phase whereby the antibody is bound by the ligand, enzymatically modifying the glycosylation at an N-glycosylation site of the antibody applying a first and second glycosylation modifying enzyme for a time sufficient and under conditions suitable to modify the glycosylation at the N-glycosylation site thereby producing a glycosylation modified antibody, and releasing the antibody and wherein the enzymes are galactosyltransferase and sialyltransferase.
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 Lily 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 paraphrase above).
Thus, the claims are drawn to a method for the enzymatic production of any glycosylation modified antibody derived from any sources having any structural feature, comprising incubating any first antibody affinity ligand-bound monoclonal antibody having any structure with a glycosylation at any N-glycosylation site with any first enzyme derived from any unknown sources having any structural feature and having glycosylation activity, for a time sufficient and under conditions suitable to modify the glycosylation at the N-glycosylation site thereby producing any first modified antibody, incubating the first modified antibody in solution with any second enzyme derived from any unknown sources having any structural feature, for a time sufficient and under conditions suitable to modify the glycosylation at the N-glycosylation site of the first modified antibody thereby producing the glycosylation modified antibody, and separating the glycosylation modified antibody, wherein the enzymes are any galactosyltransferase and any sialyltransferase (for claim 7) includes GalT1 (claim 8) and ST6 (claim 9) and GalT1 and ST6 (claim10) derived from any sources having any structure, i.e. claims are drawn to using any enzyme for glycosylation of N-glycosylation site of any antibody using any sugar residue, wherein the enzymes includes galactosyltransferase or sialyltransferase, which are derived from many unknown sources and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures. As such the claims encompass very broadly any enzymes (no enzyme name is recited in claims 3-4, 6-7) or any galactosyltransferase and any sialyltransferase derived from any unknown sources having any structural feature (for claim 7), for glycosylating N-glycosylation site of an antibody using the genus of enzyme polypeptides, glycosyltransferase or sialyltransferase, and functional homologs or variants broadly encompass in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of enzyme polypeptides is adequately described by the disclosure of the structures in the prior art, i.e., any enzymes involve in glycosylation of any antibody and using any sugars, or using any galactosyltransferase or any sialyltransferase. However, the art clearly teaches the “Practical Limits of Function Prediction”: Whisstock et al., 2003 (IDS #252 5/16/2023) 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, it is difficult to state criteria for successful prediction of function, since function is a vague concept. 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., 1999 (IDS #256 5/16/2023) teaches that one conservative amino acid substitution transforms a ketoacyl synthase into a malonyl decarboxylase and completely eliminates ketoacyl synthase activity. Similarly, the art also teaches that functionally similar molecules have different structures; Kisselev 2002 (IDS #160 5/16/2023) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
Claims are drawn to very broadly any enzyme for glycosylation derived from any unknown sources having any structural feature or any galactosyltransferase includes GalT1 or any sialyltransferase enzymes includes ST6 derived from any unknown sources having any structural feature that encompasses many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, wherein the enzymes, galactosyltransferase includes GalT1 or sialyltransferase includes ST6 enzymes has glycosylation activity, whose structures are not fully described in the specification. No information, beyond the characterization of enzymes, galactosyltransferase includes GalT1 or sialyltransferase includes ST6 enzymes derived from any unknown sources having any structural feature has been provided, which would indicate that applicants had possession of the claimed genus. The specification does not contain sufficient disclosure of the structure with function of all the enzymes, galactosyltransferase, GalT1 or sialyltransferase, ST6 enzymes or proteins within the scope of the claimed genus. The genus of enzymes, galactosyltransferase or sialyltransferase enzymes claimed is a large variable genus including many mutants, variants and fragments thereof, which can have wide variety of structures. Therefore, many structurally unrelated enzymes, galactosyltransferase or sialyltransferase enzymes within the scope of these claims. The specification discloses the structure of only few representative species of the claimed genus, which is insufficient to put one of skill in the art in possession of the attributes and features of all species within the claimed genus. Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 103
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.
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.
Claims 3-4 and 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Tayi et al. WO 2015/123754 (instant PTO-892) in view of Eifler et al., 2014 (IDS 10/17/2025).
Tayi teaches a method for enzymatically modifying an Fc region of an affinity ligand bound antibody from a heterogeneous glycoform to a homogenous single glycoform comprising contacting said affinity ligand bound heterogeneous glycoform antibody with one or more enzymes including a galactosyltransferase, including GalT1, which is a first enzyme, while being bound to an affinity ligand, and then, the antibody treated with a sialyltransferase, including ST6, which is a second enzyme, which results in the glycosylation of the antibody at N-linked glycosylation site of the antibody in the Fc region with asparagine (N297) residue (see pages 2, 19 and 22) as in instant claims 3 and 7-10. Tayi teaches that the glycosylation reaction was conducted for a time sufficient and under conditions to modify the glycoform of the Fc region to a substantially homogeneous single form and releasing followed by separating the homogeneous single glycoform antibody sample from said affinity ligand for use in the down-stream applications, wherein the antibody is a monoclonal antibody, an IgG1-4 monoclonal antibody, wherein said monoclonal antibody is fact bivalent monospecific antibody because it has two Fab antigen binding region as well as the antibody can be chimeric, humanized and human type (see, abstract, page 7-8, 14-15, 16, Claim 40) as in instant claims 3-4, 6 and 8-10. Tayi teaches an in-vitro modification of N-glycan of antibodies, which was conducted by bound antibodies to an affinity ligand, where HP spin-trap Protein A column was used (see, page 33) for in vitro modification of N-glycan of the antibodies, wherein a reaction mixture, containing specific enzymes, which were added as discussed above, i.e. galactosyltransferase or sialyltransferase enzyme was added to the column sequentially with a step of washing to remove unbound chemicals and enzymes, releasing enzymes to collect for reuse, with nucleotide sugars (activated sugar) and cofactors and the column were incubated at 37oC for a specific time period including 24-48hrs for N-glycan modification and followed by sialyltransferase enzyme solutions for second N-glycosylation in N-glycan of the antibody, and the modified antibodies are purified by washing with buffer and eluting the modified N-glycosylated antibodies released from HP spin-trap Protein A column. Since, the modification occurred even when bound to the affinity ligands, so that the modification can be carried out continuously or repeatedly as needed (page 12-13, 15, 34-35, and 42), which is clearly shown step by step in wash step, reaction step, wash step, reaction step and wash step, elution step and recovering step of glycosylated antibody in Figure 1 as in instant claims 3 and 8-10. Tayi also teaches a biopharmaceutical composition comprising said modified antibody having glycosylation at the Fc region with pharmaceutical acceptable carriers for treating diseases like cancer as medicament for immunotherapy (see, abstract, page 5, 6, 7-8, 9, 10, 22, 30, Claims 1-67, and Fig. 1 as shown below).
PNG
media_image1.png
709
1570
media_image1.png
Greyscale
While Tayi teaches using an antibody ligand bound to a solid phase, and teaches that any ligand that has affinity towards antibodies can be used for these methods (see page 25, 3rd and 4th paragraph), Tayi does not teach using an antibody light chain affinity ligand bound to the solid phase as required in instant claim 3.
Eifler teaches a novel affinity chromatography resin for the platform purification of lambda Fabs (see abstract; lambda refers to one of the two isoforms (kappa and lambda) light chain of an antibody). Eifler teaches that Protein A chromatography while effective for the purification of many antibodies is not effective for the purification of human Fabs (see page 1311). Eifler teaches that the constant domain of the kappa and lambda light chain help produce the LambdaFabSelect and KappaSelect affinity ligands for a generic approach for the purification of any type of antibody format carrying a constant human light chain (see page 1312, paragraph spanning 1st and 2nd column) and meets the requirement of the antibody light chain affinity ligand of instant claim 3. Eifler does not teach the glycosylation method of the instant claims.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Tayi and Eifler. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Tayi already teaches the glycosylation method of the instant claims and also teaches that any ligand that has affinity towards antibodies can be used for these methods (see page 25, 3rd and 4th paragraph). Therefore, one of ordinary skill in the art would be motivated to modify the affinity ligand and use the antibody light chain affinity ligand taught by Eifler since Eifler teaches that these affinity ligands are better at capturing a wider range of antibodies in comparison the other ligand already being used in the purification method. Further, the methods may be modified to determine the best time for incubation with the enzymes and in what order because optimization is a matter of routine experimentation in the absence of unexpected results to obtain better results in terms of enhanced modified protein production, which is well known in the art. It is well established that merely selecting proportions, ranges and modifying the process conditions such as temperature, reaction time and concentration as well as process steps is not a patentable modification absent a showing of criticality (In re Aller, 220 F.2d, 454, 105 U.S.P.Q 233 C.C.P.A, 1995 and In re Becket, 33 U.S.P.Q 33, C.C.P.A, 1937 and In re Russell, 439 F. 2d 1228, 169 U.S.P.Q. 426, C.C.P.A 1971). The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references Tayi successfully produced highly purified glycosylated antibody composition for treating cancer and immune disorders.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 3-4 and 6-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,767,342. Although the claims at issue are not identical, they are not patentably distinct from each other because the same method of for the enzymatic production of a glycosylation modified antibody comprising incubating an antibody light chain affinity ligand-bound monoclonal antibody with a glycosylation at a N-glycosylation site with a first and second enzyme having glycosylation activity, for a time sufficient and under conditions suitable to modify the glycosylation at the N-glycosylation site thereby producing a glycosylation modified antibody, and separating the glycosylation modified antibody. Therefore, the ‘342 claims anticipate the instantly claimed invention.
Claims 3-4 and 6-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No.12,269,867. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘867 claims the same method of for the enzymatic production of a glycosylation modified antibody comprising incubating an antibody light chain affinity ligand-bound monoclonal antibody with a glycosylation at a N-glycosylation site with a first and second enzyme having glycosylation activity, for a time sufficient and under conditions suitable to modify the glycosylation at the N-glycosylation site thereby producing a glycosylation modified antibody, and separating the glycosylation modified antibody. Therefore, the ‘867 claims anticipate the instantly claimed invention.
Conclusion
No claims are allowed.
Advisory Information
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AURORA M. FONTAINHAS whose telephone number is 571-272-2952. The examiner can normally be reached on Monday - Friday (8AM - 4PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached on (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300./AURORA M FONTAINHAS/ /AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
Prosecution Insights