DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/18/2026 has been entered.
Priority
This application claims benefit of priority to Provisional Application 63/221,436 filed on 07/13/2021.
Amendments and Claim Status
In the reply filed 05/18/2026, Applicant amended claim 1. Claim 8 was previously canceled.
Claims 1-7 and 9-18 are currently pending and under examination.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 and 9-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite “characterizing at least one product-related variant,” “determining an amount of the target to be immobilized on beads by a titration curve” and “comparing the abundance of said at least one product-related variant … to characterize said at least one product-related variant.”
The limitations of characterizing at least one product-related variant by comparing values, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process. That is, nothing in the claim precludes the step from practically being performed in the mind. For example, “characterizing” in the context of this claim encompasses the user manually characterizing the variant based upon a comparison of a control and an amount of a variant. Further, “determining” in the context of this claim encompasses the user looking at a titration curve and determining in the mind an amount of target to utilize. “Comparing” in the context of this claim encompasses the user thinking about the amount of product-related variant in the flow-through and the amount of product-related variant in the control sample and making a mental determination about the correlation. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind, then it falls within the “Mental Processes” grouping of abstract ideas. As such, the claims recite an abstract idea.
This judicial exception is not integrated into a practical application. In particular, the claims only recite steps regarding data gathering to perform the comparing steps so that the product-related variant can be characterized. The data gathering in all steps of the method are recited at a high-level of generality such that it amounts to no more than mere instructions to apply the exception. Accordingly, these additional steps do not integrate the abstract idea into a practical application because they do not impose any meaningful limits on practicing the abstract idea. Therefore, the claims are directed to an abstract idea.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to integration of the abstract idea into a practical application, the additional elements of data gathering steps amount to no more than mere instructions to apply the exception. Mere instructions to apply an exception using data gathering steps cannot provide an inventive concept. Additionally, the steps of obtaining a sample, contacting the sample to a target, collecting a flow-through, contacting the flow-through to a separation column and analyzing the resultant data are all well-understood, routine and conventional steps, as discussed in the prior art and explained below. Thus, the claims are not patent eligible.
It is further noted the ‘sample’ which includes a protein of interest and a product-related variant is broad enough to read on a natural product. For example, the ‘sample’ could be blood or saliva, both natural products that are not eligible subject matter under 35 U.S.C. 101.
For the forgoing reasons, the invention as claimed is not deemed to encompass patent eligible subject matter under 35 U.S.C. 101.
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.
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.
Claims 1, 4-6 and 9-18 are rejected under 35 U.S.C. 103 as being unpatentable over Bondarenko et al. (WO 2020/247790 A1, 10/12/2020) (Of Record) in view of Piehler et al. (Journal of Immunological Methods, 1997).
Regarding claim 1, Bondarenko et al. disclose methods of identifying structures, e.g., attributes, of a therapeutic protein or a target that affect an interaction between the therapeutic protein and the target (See entire reference, Abstract). Broadly, the method of Bondarenko et al. includes:
(a) Applying a stress to a first sample comprising therapeutic proteins or targets; (b) contacting the first sample with a second sample comprising targets or therapeutic proteins to form a mixture comprising (i) therapeutic protein-target complexes, (ii) unbound therapeutic proteins, and (iii) unbound targets; and (c) separating the mixture into at least two fractions, wherein an unbound fraction comprises unbound therapeutic proteins or unbound targets and a bound fraction comprises therapeutic protein-target complexes; and (d) for each of the unbound fraction and bound fraction, identifying and quantifying the abundance of the structures, e.g., attribute, present on a species of the therapeutic protein or target (Abstract).
Additionally, the therapeutic protein binds to a target with a requisite affinity and specificity (Paragraph [0036]). The therapeutic protein has a high-affinity for the target and thus will bind a greater amount of the target in a shorter period of time than low-affinity therapeutic protein (Paragraph [0036]). The affinity of the therapeutic protein for the target is expressed in terms of an equilibrium association constant, KA (Paragraph [0036]). KD is the equilibrium dissociation constant which is a ratio of koff/kon between the therapeutic protein and the target, thus, KA and KD are inversely related (Paragraph [0037]). The KD value relates to the concentration of the therapeutic protein (the amount of therapeutic protein needed for a particular experiment) and so the lower the KD value (lower concentration), the higher the affinity of the therapeutic protein (Paragraph 0037]). Bondarenko et al. go on to state their goal is to identify critical quality attributes that result in the loss of binding (Paragraph [00150]). Protein-ligand complexes, including antibody-target remain bound during SEC separation if the equilibrium dissociation constant is Kd < 108 M (Paragraph [00150]). Bondarenko et al. applied their method to multiple antibody:target complexes by mixing them in a ratio defined by stoichiometry of interaction, typically 1:2 (Paragraph [00150]). In the case of antibody Fler2 complex, modifications after stress did not lead to loss of binding, suggesting a Kd < 108 M even for stressed molecules (Paragraph [00150]). When a smaller amount of receptor was provided, being 1:1, the antibody species with modifications reducing binding would elute as unbound (Paragraph [00150]). The disclosure of Bondarenko et al. of using the smaller amount of receptor, 1:1, leading to reduced binding among antibody species with modifications so the unbound would elute, reads on determining an amount of capture molecule immobilized on a solid surface to contact with the sample wherein the solid surface binds a determined percentage and the percentage is less than 100%.
Bondarenko et al. disclose a specific example, Example 3, utilizing affinity chromatography precipitation wherein beads labeled with the target are used (Paragraph [00125]). Specifically, in this example, affinity separation (affinity enrichment) of strongly-bound therapeutic protein-target complexes and unbound modified therapeutic protein is performed using binding targets immobilized onto resin beads and the beads are placed in an affinity chromatography column (Paragraph [00126]). Next, therapeutic proteins are stressed and mixed with the beads and an aliquot of the mixture is injected onto the affinity chromatography column (Paragraph [00127]). Fractions are eluted off the column with an appropriate elution buffer so that the bound fraction comprising the therapeutic protein-binding target complexes are retained on the column while the unbound fraction comprising therapeutic proteins not bound to the binding targets elute from the column (Paragraph [00127]). Thus, the fraction eluted does not contain the target as the target was immobilized on the beads and was retained on the column while the flow-through from the column contained therapeutic proteins that did not bind to the target.
Bondarenko et al. further disclose a competitive size exclusion chromatography (SEC) affinity separation for identification of antibody modifications impacting binding to target protein (Paragraph [00144]). More specifically, assessment of attributes by competitive affinity binding between an antibody and its target Her2, followed by SEC fractionation and LC-MS peptide mapping (Paragraph [00146]). In one iteration of the method, the critical quality attributes responsible for the loss of binding were identified (Paragraph [00150]).
Also, it would have been obvious to one of ordinary skill in the art that beads with a determined amount of target, a 1:1 or 1:2 ratio, would be used because as discussed above, affinity separation of strongly-bound therapeutic protein-target complexes and unbound modified therapeutic protein is performed using binding targets immobilized onto resin beads and the beads are placed in an affinity chromatography column (Paragraph [00126]). Next, therapeutic proteins are stressed and mixed with the beads and an aliquot of the mixture is injected onto the affinity chromatography column (Paragraph [00127]). Fractions are eluted off the column with an appropriate elution buffer so that the bound fraction comprising the therapeutic protein-binding target complexes are retained on the column while the unbound fraction comprising therapeutic proteins not bound to the binding targets elute from the column (Paragraph [00127]). Thus, before the SEC fractionation and LC-MS peptide mapping, beads would have been used to capture the protein-target complexes, the beads would be put in an affinity chromatography column, fractions would be eluted producing a flow-through, and the flow-through would be subjected to SEC fractionation and LC-MS peptide mapping. Additionally, absent evidence to the contrary, it would be expected that the flow-through, which contains therapeutic proteins that did not bind to the target, would contain protein of interest and at least one attribute as there is not enough target to bind everything, meaning protein of interesting and attributes of the protein of interest would be left unbound and would elute.
Bondarenko et al. further disclose the use of a control, wherein the control was just antibody, a completely unbound fraction (Paragraph [00114]). It is further evident the control did not contain any target due to Bondarenko et al. delineating a specific fraction as ‘completely unbound antibody’ based upon the fraction having the same elution time as the control (Paragraph [00114]). Bondarenko et al. go on to state the data obtained from LC-MS peptide mapping leads to the identification and quantification of the abundance of each species of each fraction (Paragraph [0068]).
Bondarenko et al. do not disclose each limitation present in claim 1 as instantly-claimed within one, single embodiment nor do Bondarenko et al. disclose utilizing a titration curve to determine the amount of target to immobilize on beads as recited in part (b).
However, even though Bondarenko et al. do not disclose each limitation within one, single embodiment, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the multiple methods of Bondarenko et al. because all of the methods are directed to identifying attributes of therapeutic proteins motivated by the desire to accurately identify the different attributes of the therapeutic proteins to determine if the attributes affect the interaction between the therapeutic protein and the target as taught by the prior art and discussed above.
Additionally, Piehler et al. disclose a method for determining affinity constants based on equilibrium binding between an analyte and an antibody (See entire document, Abstract). The strong and specific binding of target molecules to the binding sites of an antibody plays an important role in several fields of analytical chemistry (Page 189, Last Sentence). The interaction between target molecules, or analytes, with the antibody is characterized by its affinity constant K defined by the equilibrium concentrations of analyte-antibody complex, free analyte and free antibody binding sites (Page 190, First Sentence). The assessment of affinity constants is of fundamental importance, in particular for the characterization of monoclonal antibodies with respect to their analytical performance and cross reactivity (Page 190, Paragraph 1). Methods for determining affinity constants are usually based on the determination of the equilibrium concentrations of the reactants (Page 190, Paragraph 1). The association and dissociation rate constants of the interaction are derived from binding curves wherein the affinity constant is determined from the ratio of the rate constants or the equilibrium coverage (Page 190, Paragraph 2). For the assessment of titration curves the equilibrium concentration of free antibody binding sites has to be determined for a constant antibody concentration and various analyte concentrations (Page 197, Paragraph 2). The concentration of free antibody binding sites was titrated by adding increasing analyte concentrations and the affinity constant was derived from a titration curve (Abstract). When the affinity constant is low, the antibody-analyte complex tend to dissassociate (Abstract).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized a titration curve to determine the affinity constant of the therapeutic proteins for the target in the method of Bondarenko et al. motivated by the desire to provide an adequate amount of target for variants where the affinity for the target is not reduced to bind to the target so they can be identified which is the goal of Bondarenko et al. It would have been obvious to utilize a titration curve to determine the amount of target needed because titration curves show the affinity constant of the antibody to the analyte which shows the amount of antibody expected to be bound and unbound at differing amounts of analyte as taught by Piehler et al. Therefore, it would have been obvious to utilize a titration curve to select an amount of target to immobilize that would provide enough target for variants without a reduced affinity constant to bind but not so much target that variants with reduced affinity constants would also bind so that variants with modifications reducing binding would elute as unbound which would enable one to distinguish between variants that affect an interaction between the protein of interest and the target from attributes that do not affect the interaction as is the goal of Bondarenko et al.
Regarding claim 4, as disclosed above regarding claim 1, Bondarenko et al. disclose Example 3 utilizing affinity chromatography precipitation wherein beads labeled with the target are used (Paragraph [00125]). Specifically, in this example, affinity separation (affinity enrichment) of strongly-bound therapeutic protein-target complexes and unbound modified therapeutic protein is performed using binding targets immobilized onto resin beads and the beads are placed in an affinity chromatography column (Paragraph [00126]). Next, therapeutic proteins are stressed and mixed with the beads and an aliquot of the mixture is injected onto the affinity chromatography column (Paragraph [00127]). Fractions are eluted off the column with an appropriate elution buffer so that the bound fraction comprising the therapeutic protein-binding target complexes are retained on the column while the unbound fraction comprising therapeutic proteins not bound to the binding targets elute from the column (Paragraph [00127]). Thus, under the broadest reasonable interpretation, as enriching simply means concentrating the desired component, the flow-through containing only unbound therapeutic proteins reads on being enriched for at least one product related variant as the therapeutic protein variants are what was not binding/had reduced binding and the bound therapeutic protein target complexes were retained on the column, increasing the concentration of, or enriching, the therapeutic protein variants in the flow-through.
Regarding claim 5, Bondarenko et al. further disclose centrifuging to obtain a supernatant (i.e., flow-through) of the unbound and of the bound fraction (Claim 29 of Bondarenko et al.).
Regarding claim 6, Bondarenko et al. additionally disclose wherein the unbound fraction and bound fraction are subjected to a peptide digestion step prior to the quantifying step or identifying and quantifying step (Claim 33 of Bondarenko et al.).
Regarding claims 9 and 10, Bondarenko et al. do not disclose incubation for one hour or incubation at about room temperature.
However, Bondarenko et al. further disclose where therapeutic proteins are stressed and subsequently mixed with the beads covered with the binding targets. For the first subgroup, an aliquot of the mixture is injected onto the affinity chromatography column. For the second subgroup, the centrifuge tubes are gently rocked overnight. For the second group, the cells expressing the binding targets at the cell surface are mixed with the stressed therapeutic proteins and incubated in centrifuge tubes with gentle rocking. After the mixing, the centrifuge tubes are centrifuged to separate the beads comprising the bound fraction comprising therapeutic protein-binding target complexes from the unbound fraction comprising therapeutic proteins unbound to binding target (Paragraph [00127]).
Accordingly, from the above disclosure, Bondarenko et al. disclose incubation. Since it appears that incubation is a necessary step to obtain beads comprising therapeutic protein-binding target complexes, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed incubation time and temperature based on the degree of binding one desires. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Regarding claim 11, Bondarenko et al. further disclose wherein the mixture is separated into at least two fractions using a technique that separates components of a mixture based on size (Claim 27 of Bondarenko et al.).
Regarding claim 12, Bondarenko et al. further disclose wherein the method is used for detecting fragmentation/clipping (Paragraph [0062]).
Regarding claim 13, Bondarenko et al. further disclose wherein the attribute forms as a result of a chemical modification and wherein the chemical modification is aggregation (Claims 51 and 52 of Bondarenko et al.).
Regarding claim 14, Bondarenko et al. further disclose wherein the attribute forms as a result of chemical modification and wherein the chemical modification alters the mass-to-charge ratio of charged ions of an amino acid of the therapeutic protein (Claim 51 of Bondarenko et al.).
Regarding claim 15, Bondarenko et al. further disclose wherein attributes include post-translational modifications of the therapeutic protein (Paragraph [00146]).
Regarding claim 16, Bondarenko et al. further disclose wherein the therapeutic protein can comprise an antibody, and the target can comprise an antigen for the antibody (Paragraph [0032]).
Regarding claim 17, Bondarenko et al. further disclose that when the abundance of a structure, e.g., attribute, in the unbound fraction is greater than the abundance of the structure, e.g., attribute, in the bound fraction, the structure, e.g., attribute, negatively affects the interaction between the therapeutic protein and the target (Paragraph [0005]).
Regarding claim 18, Bondarenko et al. disclose a stress that causes an about 10% to about 50% reduction in interactions, relative to interactions in corresponding conditions lacking the stress (Paragraph [0055]). Further, the stress causes an increase in the KD of the therapeutic protein for its target which KD is associated with weaker binding (Paragraph [0055]). Thus, assuming an initial binding interaction to be 100%, a reduction of about 10% to about 50% binding would result in about 50% to about 90% binding interaction, which overlaps with the claimed range of about 30% to about 80%. Therefore, given the broadest reasonable interpretation, Bondarenko et al. teach at least one product-related variant having compromised binding with the target and an amount of target capable of binding to about 30% to about 80% of the protein of interest.
Claim 1-2, 4-6 and 9-18 are rejected under 35 U.S.C. 103 as being unpatentable over Bondarenko et al. (WO 2020/247790 A1, 10/12/2020) (Of Record) and Piehler et al. (Journal of Immunological Methods, 1997), and further in view of Yan et al. (Analytical Chemistry, 10/03/2018) (Of Record).
The teachings of Bondarenko et al. and Piehler et al. are discussed above.
Regarding claim 2, neither Bondarenko et al. nor Piehler et al. disclose wherein the liquid chromatography is strong cation exchange chromatography.
However, Yan et al. teach the use of strong cation exchange chromatography. Yan et al. disclose a method that combines a generic strong cation exchange (SCX) chromatography step with ultrasensitive online native MS analysis (SCX-MS) optimized for mAb separation and detection (Abstract). The combination of efficient upfront chromatographic separation and highly sensitive MS analysis allows the detection of minor variants present at very low levels (Results and Discussion).
As such, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used strong cation exchange chromatography with SCX-MS in the method of Bondarenko et al. motivated by the desire to detect a product-related variant that may be present only in low abundance as taught by Yan et al.
Claims 1, 3-7 and 9-18 are rejected under 35 U.S.C. 103 as being unpatentable over Bondarenko et al. (WO 2020/247790 A1, 10/12/2020) (Of Record) and Piehler et al. (Journal of Immunological Methods, 1997), and further in view of Polukhtin et al. (US 20160370376 A1, 12/22/2016) (Of Record).
The teachings of Bondarenko et al. and Piehler et al. are discussed above.
Regarding claims 3 and 7, neither Bondarenko et al. nor Piehler et al. disclose wherein said beads are magnetic beads or coated with streptavidin resin.
However, Polukhtin et al. disclose a method for the detection and isolation of targets from heterologous mixtures (See entire reference, Paragraph [0002]). Polukhtin et al. further disclose a method to detect a molecule by using binding molecules that have a specific affinity for another molecule, such as the binding of an antigen to an antigen-specific antibody, wherein either the antigen or antibody is immobilized on a solid support, such as a magnetic bead, and used to isolate the target molecule (Paragraph [0005]). More specifically, biotin or a biotin derivative is bound directly to a target molecule, such as a protein, and then interacted with streptavidin or avidin conjugated to an affinity medium like a magnetic bead and then used to isolate a target (Paragraph [0007]).
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized magnetic beads or beads coated with streptavidin resin in the method of Bondarenko et al. to effectively immobilize the target onto the bead as taught by Polukhtin et al. as this was a known and effective means of immobilizing a target onto a bead.
USC § 103 – Response to Arguments
Applicant's arguments filed 05/18/2026 have been fully considered but they are not persuasive.
Applicant argued Bondarenko et al. do not determine a reduced amount of target immobilized on beads for capturing or binding a determined percentage of protein in a sample (Page 5, Last Paragraph).
The Examiner respectfully disagrees. It remains the Examiner’s position, as stated in the Advisory Action mailed 06/08/2026, that Bondarenko et al. do teach this limitation. Bondarenko et al. specifically teach a 1:2 and a 1:1 ratio, when the 1:1 ratio is used the antibody with modifications has reduced binding and would elute. Thus, Bondarenko et al. determine the 1:1 ratio, reading on a reduced amount of target as a 1:1 ratio is less than a 1:2 ratio, would capture a smaller percentage of protein.
Applicant argued Bondarenko et al. teach separating a protein of interest and its variants, including SEC, prior to mass spectrometry analysis (Page 6, Paragraph 1).
The instant claims recite “subjecting said flow-through to liquid chromatography-mass spectrometry analysis to separate said protein of interest and said at least one product-related variant” in part (e) of instant claim 1. Size exclusion chromatography (SEC) is a type of liquid chromatography. Thus, the instant claim recites what Applicant is arguing against as the instant claim recites ‘liquid chromatography-mass spectrometry,’ meaning liquid chromatography prior to mass spectrometry.
Applicant argued the multiple embodiments of Bondarenko et al. cannot be conflated.
The Examiner respectfully disagrees. As stated above on Page 9, even though Bondarenko et al. do not disclose each limitation within one, single embodiment, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the multiple methods of Bondarenko et al. because all of the methods are directed to identifying attributes of therapeutic proteins motivated by the desire to accurately identify the different attributes of the therapeutic proteins to determine if the attributes affect the interaction between the therapeutic protein and the target. All of the methods utilized within Bondarenko et al. are known and utilized for separating and identifying proteins, and attributes or variants of proteins, and would therefore be obvious to utilize in a method for said purpose.
Applicant further argued Bondarenko et al. do not disclose or remotely implicate the use of a titration curve as is now required by amended claim 1 (Page 7).
The Examiner agrees that Bondarenko et al. do not disclose the use of a titration curve. However, an amended rejection has been set forth above addressing this new limitation.
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 1-7 and 9-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 and 35-36 of copending Application No. 17885805 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of both applications are directed to a method for characterizing a variant of a protein of interest. Claim 1 of ‘805 recites:
A method to produce a flow-through for characterizing at least one post-translational modification (PTM) in a protein of interest, comprising:
Providing a sample including a protein of interest, wherein the protein of interest features at least one PTM;
Determining an amount of capture molecule to be immobilized on a solid surface by a titration curve which relates percentages binding of the protein of interest to amounts of capture molecule immobilized on the solid surface, and immobilizing the determined amount of capture molecule on the solid surface to contact with said sample, wherein the determined amount of the capture molecule immobilized on the solid surface binds a determined percentage of the protein of interest and wherein the determined percentage is less than 100%;
Contacting the sample with said determined amount of the capture molecule immobilized on the solid surface;
Collecting unbound protein of interest to produce a flow-through;
Contacting said flow-through to a separation column to separate at least one variant of said protein of interest featuring at least one PTM;
Quantitating an amount of said at least one variant and comparing said amount to an amount quantitated in a control sample to characterize the at least one PTM in said protein of interest.
It is noted a post translation modification is a type of product-related variant of a protein as evidenced by instant claim 15. While claim 1 of ‘805 utilizes slightly different wording, the method is patentably indistinct from claim 1 of the instant application, ‘303. Claim 5 of ‘805 corresponds to instant claim 16. Claims 6-7 of ‘805 correspond to instant claim 3. Claim 8 of ‘805 corresponds to instant claim 7. Claim 9 of ‘805 corresponds to instant claim 5. Claims 10-12 of ‘805 correspond to instant claim 2. Claims 13-14, 16 and 19 of ‘805 correspond to instant claim 6. Claim 15 of ‘805 corresponds to instant claim 4. Claim 16 of ‘805 corresponds to instant claim 6. Claim 21 od ‘805 corresponds to instant claim 1. Claim 24 and 36 of ‘805 corresponds to instant claim 18.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-7 and 9-18 are rejected.
No claims are allowed.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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