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. Information Disclosure Statement The information disclosure statements (IDS) submitted on 01/24/2024 and 12/16/2025 have been considered by the examiner. Specification The specification is objected to because of the incomprehensible components, pertinent to determining the scope of the claims. The specification defines hydrophilic as Mabs with a retention time less than or equal to rituximab. {Page 59} Retention time is dependent on many different variables, and does not have a direct causation to hydrophobicity, thus, the examiner is not able to determine the scope of the applicant’s claims. (See claim interpretation section for further clarity regarding hydrophobicity and retention times) 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. Claim s 1-15 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as based on a disclosure which is not enabling. The disclosure does not enable one of ordinary skill in the art to practice the invention without disclosing further information defining the bounds of hydrophilicity and/or hydrophobicity antibodies , which is/are critical or essential to the practice of the invention but not included in the claim(s). See In re Mayhew , 527 F.2d 1229, 188 USPQ 356 (CCPA 1976). Claim 1 claims a hydrophilic antibody and the spec defines hydrophilic as mA bs with a retention time less than or equal to rituximab. As similarly stated in the Written Opinion of the International Searching Authority submitted by the applicant, it is unusual to describe an antibody as hydrophilic . Separately claim 6 refers to the retention time of Rituximab. As stated above, the applicant intends to define the hydrophobicity of an antibody based on this retention time, however, the retention time of a ntibodies is variable based on other components such as stationary phase hydrophobicity, salt lyotropic strength, temperature, etc. {Cusumano, Page 5} and thus cannot be used as a determining factor with only the HIC retention time of rituximab ; a determination that the International Searching authority similarly concluded to as they had stated, “it was not possible to retrieve this value or the condition in which it was calculated”. The remainder of the claims are rejected due to their dependency of the claims mentioned above. Claim s 1-15 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The preamble of claim 1 states, “producing an antibody” yet, nowhere in the disclosure it producing an antibody discussed. The applicant’s specification suggests the method is referring to the purification of the antibody, as the “Field of the Invention” section discloses, “methods for the production or purification of hydrophilic antibodies”. However, this sentence alone is not enough to give the term “producing” an alternate definition making it synonymous with purifying. The remainder of the claims are rejected due to their dependency of the claims mentioned above. 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. Claim 12 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the type/contents of the solution that is loaded into the chromatography device is not clear within the steps of the claims. See claim interpretation section for how the examiner is interpreting claim 12. The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim s 3-5, and 14 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 discloses within the body of the claim “a method for producing an antibody composition with reduced antibody-related …”, while claim 1, which claim 3 depends on, discloses, “A method for producing an antibody”. Since claim 3 is attempting to claim an antibody composition that comprises the antibody, that composition has additional components, compared to the antibody mentioned in claim 1, thus broadening the scope of the claim. The remainder of the claims are rejected due to their dependency on the claim mentioned above. Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The bullet points of claim 3 stating “the antibody composition with reduced HMW impurity content and/or with reduce viral impurity content is recovered from flowthrough, and thereby an antibody composition with reduced HMW impurity content and/or with reduced viral impurity content is produced.” Fully encompasses the limitations of claim 4. Claim 4 simply restates that the impurities are reduced compared to the influent solution of this process, and given that claim 3 depends on either claim 2 or 1, wherein the influent of solution of the process is defined, the contents of claim 4 are not further limiting. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Interpretation To promote clarity and efficiency in the examination process (compact prosecution), the following terms or sections of the claims, as outlined below are interpreted, but not limited to, the following: A method for producing antibodies will be interpreted as, “A method for the purification of antibodies” Hydrophilic and hydrophobic will be interpreted as any material that exhibits characteristics that can place in on a hydrophobicity scale . This interpretation was made in light of the applicant’s disclosure failing to create clear bounds of the terms. The retention time of Rituximab will be interpreted as a variable value , given in light of Non-Patent Literature Cusumano, attached to this correspondence, explains how the retention time of antibodies is variable based on other components of the chromatography process. Claim 12 will be interpreted as, “ The method according to claim 1 wherein the loaded amount, of the solution comprising the antibody and the antichaotropic salt, to the MM HIC/IEX is from 15 g of protein per Liter of chromatography material (15 g/L) to 350 g of protein per Liter of chromatography material (350 g/L).” 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 . Claims 1- 6, 8-9 , 11, 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Hunter (US20160083453A1) in view of Cusumano ( NPL - Practical method development for separation etc. ). In regards to claim 1, Hunter teaches a method for producing an antibody using a mixed mode chromatography material that comprises ion exchange functional groups and hydrophobic interaction functional groups (MM HIC/IEX) {Page 6 paragraph 87, "multi-modal chromatography resins … that have both ion exchange properties as well as with hydrophobic interaction properties"} operated in flow through mode, {Page 6 paragraph 87, "For multi-modal resins … mAbs can be processed … in flowthrough mode"} wherein b) the antibody is applied in a solution comprising the antibody and an antichaotropic salt to the MM HIC/IEX. {Page 7 paragraph 88, "multimers were reduced … in the Capto Adhere pool … Under these optimizes load conditions (… 100mm NaCl)} In regards to claim 2, Hunter teaches the method according to claim 1, wherein the method further comprises the following steps: c) optionally a rinsing solution is applied, d) the antibody is recovered in the flowthrough of b) or optionally in the flowthrough of b) and c), and thereby producing the antibody using a MM HIC/IEX operated in flowthrough mode and thereby producing the antibody using a MM HIC/IEX operated in flowthrough mode. {Page 7 paragraph 88, "multimers were reduced from 3.4% in the load, to 0.8% in the Capto Adhere pool"} Hunter explaining the % of multimers in the pool, shows that the solution was recovered , thereby teaching step “d” of the claims. In regards to claim 3, Hunter teaches the method according to claim 1 or claim 2, wherein - the method is for producing an antibody composition with reduced antibody-related high molecular weight (HMW) impurity content and/or with reduced viral impurity content, {Page 2 paragraph 27, ""Multimer" means high molecular weight aggregates of antibodies" and Page 7 paragraph 88, "multimers were reduced"} - the antibody is applied to the MM HIC/IEX in a solution comprising the antibody, at least one HMW impurity, and/or at least one viral impurity and the antichaotropic salt {Page 4 paragraph 51, "where monomers and multimers are both bound to the column and then the monomers are selectively eluted with a change in salt concentrations … or under flowthrough conditions"} - the antibody composition with reduced HMW impurity content and/or with reduced viral impurity content is recovered from the flowthrough, thereby an antibody composition with reduced HMW impurity content and/or with reduced viral impurity content is produced. {Page 2 paragraph 27, ""Multimer" means high molecular weight aggregates of antibodies" and Page 7 paragraph 88, "multimers were reduced"} In regards to claim 4, Hunter teaches the method according to claim 3, wherein the HMW impurity content and/or the viral impurity content is reduced compared to the solution applied to the MM HIC/IEX in step b). {Page 2 paragraph 27, ""Multimer" means high molecular weight aggregates of antibodies" and Page 7 paragraph 88, "multimers were reduced from 3.4% in the load, to 0.8% in the Capto Adhere pool"} In regards to claim 5, Hunter teaches the method according to claim 3, wherein the HMW impurity content and/or the viral impurity content is reduced compared to a solution essentially without an antichaotropic salt; and/or compared to a solution comprising a hydrophobic antibody. {Page 7 paragraph 88, "multimers were reduced … in the Capto Adhere pool … Under these optimizes load conditions (… 100mm NaCl)} Given that Hunter teaches the salt solution that is claimed by the applicant, Hunter would inherently teach the effect of the salt solution performing better compared to a separate/different type of solution going through the same chromatography method. In regards to claim 8, Hunter teaches the method according to claim 1, wherein the antichaotropic salt has a molar surface tension increment in the range of and including 1.285 to 4.183 x 10E3 dyn *g*cm-1*mol-1. {Page 7 paragraph 88, "Under these optimized conditions (pH 5.0. 100mM NaCl)"} The instant application initially had claim 9 (which claimed NaCl and other salts) depend on this claim 8. While Hunter does not explicitly teach the molar surface tension of NaCl, it can be assumed NaCl under the claimed concentrations of this solution, would inherently exhibit the molar surface tension parameters claimed by the applicant. In regards to claim 9, Hunter teaches the method according to claim 1, wherein the antichaotropic salt is selected from the group consisting of (NH4)2SO4, Na2SO4, K2S04, NaCl and KCl . {Page 7 paragraph 88, "Under these optimized conditions (pH 5.0. 100mM NaCl)"} In regards to claim 11, Hunter teaches the method according to claim 1, wherein in the solution comprising the antibody and the antichaotropic salt, the antichaotropic salt has a concentration of from 10 mM to 900 mM. {Page 3 paragraph 38, "The buffer comprises 0-1M sodium chloride"} In regards to claim 13, Hunter teaches the method according to claim 1, wherein the solution comprising the antibody and the antichaotropic salt has a pH value from 4.0 to 9.0. {Page 3 paragraph 39, "In some embodiments … pH is in the range of about 3.0 to 6.0"} and {Page 3 paragraph 40, "In some embodiments, the pH is in the range of about 6.0 to 10.0"} In regards to claim 15, Hunter teaches the method according to claim 1, wherein the MM HIC/IEX comprises i ) Anion exchange functional groups or cation exchange functional groups, ii) or strong anion exchange functional groups, iii) or weak cation exchange functional groups. {Page 6 paragraph 87, "AEX/HIC ligands, mAbs can be processed" (AEX abbreviated for anion exchange membrane)} Hunter does not teach: Claim 1: wherein a) the antibody is a hydrophilic antibody Claim 6: The method according to claim 1, wherein the hydrophilic antibody is an antibody that has a retention time on a hydrophobic interaction chromatography (HIC) material that is equal or less than that of rituximab. However, Cusumano teaches all of the limitations of these claims that Hunter does not teach. In regards to claim 1, Cusumano teaches wherein a) the antibody is a hydrophilic antibody. {Middle page 4 left column, "order of their hydrophobicity (HIC elution order based on preliminary study): denosumab (huIgG2, pI = 8.8), palivizumab (hzIgG1, pI = 9.0), pertuzumab (hzIgG1, pI = 8.7), rituximab (chIgG1, pI = 9.1) and bevacizumab (hzIgG1, pI = 8.5)."} In regards to claim 6, Cusumano teaches the method according to claim 1, wherein the hydrophilic antibody is an antibody that has a retention time on a hydrophobic interaction chromatography (HIC) material that is equal or less than that of rituximab. {Middle page 2 left column, "Real life samples such as denosumab, palivizumab, pertuzumab , rituximab and bevacizumab and a cysteine linked ADC (brentuximab- vedotin ) … are presented here as case studies." and Bottom page 5 right column, "Retention and selectivity in the HIC can be tuned by several means of several operating parameters, such as stationary phase hydrophobicity, salt lyotropic strength, gradient program, temperature, organic modifier"} It would have been obvious to, and one of ordinary skill in the art prior to the effective filing date of the claimed invention, would be motivated to combine the teachings on Cusumano with the invention of Hunter because the purpose Cusumano was to evaluate the performance the common protein purification chromatography processes through of changing variables, which highly relates , within the same field of endeavor, to the invention of Hunter. The goal of the study was to utilize what they learned regarding the importance of each variable for the efficiency of the process, to develop a fast and automated “phase system”, which would be an improvement over what was available during the time of the study. {Cusumano, Abstract} Claims 7, 12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Hunter (US20160083453A1) and Cusumano (NPL - Practical method development for separation etc ), in view of Menegatti (WO2020112906A1). The combination of Hunter and Cusumano teach all of the limitations of claims 1-6, 8-9, 11, 13, and 15, as mentioned in the prior 103 rejection. This combination does not teach: Claim 7: The method according to claim 6, wherein the HIC material contains polyether groups (ethyl ether groups) as ligand. Claim 12: The method according to claim 1, wherein the loaded amount to the MM HIC/IEX is from 15g of protein per Liter of chromatography material (15g/L) to 350g of protein per Liter of chromatography material (350g/L) Claim 14: The method according to claim 3, wherein the HMW impurity is an impurity which has a molecular weight of 285 kDa or more. However, Menegatti teaches all of the limitations that the combination of Hunter and Cusumano does not teach. In regards to claim 7, Menegatti teaches the method according to claim 6, wherein the HIC material contains polyether groups (ethyl ether groups) as ligand. {Page 13 paragraph 56, "Supports may comprise … resins … Suitable synthetic polymers include … polyethersulfone "} and {Page 16 paragraph 70, "development of an ensemble of ligands capable of specific capture of HCPs in flow through mode"} In regards to claim 12, Menegatti teaches the method according to claim 1, wherein the loaded amount to the MM HIC/IEX is from 15g of protein per Liter of chromatography material (15g/L) to 350g of protein per Liter of chromatography material (350g/L) {Page 52 paragraph 125, "Pure mAb at 0.1, 0.5, 1.0, 2.5, and 5.0 mg/mL was utilized to construct the curve"} and {Page 57 paragraph 140, "highest load tested, "200 mg/mL for all resins"} Note, that the concentrations of mg/mL convert directly to g/L, ex. 5mg/mL = 5g/L. While Menegatti does not teach the entire claimed range of the applicant 15-350 g/L, they teach low - end experimental concentrations of down to 0.1mg/mL and high - end experimental concentrations of 200mg/ mL. "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." MPEP 2144.05 In regards to claim 14, Menegatti teaches the method according to claim 3, wherein the HMW impurity is an impurity which has a molecular weight of 285 kDa or more. {Page 58 paragraph 141, "high molecular weight (MW > 150 kDa "} It would have been obvious and one to one of ordinary skill in the art prior to the effective filing date of the claimed invention would be motivated to combine the invention of Menegatti to the combined invention of Hunter and Cusumano because these inventions both teach hydrophobic interaction chromatography for protein purification. Specifically, one would find it obvious to combine these references because Menegatti teaches improvements over the combined system of Hunter and Cusumano . The combined invention of Hunter and Cusumano utilizes a hydrophilic antibody and Capto resin during the process, and Menegatti states that the 6HP resin was also successful in binding theses HCPs compared to Capto Q, showing significantly lower spectral abundance for 22 of the 37 investigated species. Claim FILLIN "Insert the claim numbers which are under rejection." \d "[ 1 ]" 10 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Hunter (US20160083453A1) and Cusumano (NPL - Practical method development for separation etc ) , in view of a separate embodiment of Hunter (US20160083453A1). The combination of Hunter and Cusumano , as mentioned in prior 103 rejections, teach all of the limitations of claims 1- 6 , 8 -9, 11, 13, and 1 5. They do not teach: Claim 10: The method according to claim 1, wherein the solution comprising the antibody and the antichaotropic salt of step b has a conductivity of from 0.5 to 120 mS/cm. However, a separate embodiment of Hunter, teaches all of the limitations, that the combined invention of Hunter and Cusumano does not teach. In regards to claim 10, Hunter further teaches the method according to claim 1, wherein the solution comprising the antibody and the antichaotropic salt of step b has a conductivity of from 0.5 to 120 mS/cm. {Page 4 paragraph 63, "conductivity from greater than 200 mS/cm to less than 1mS/cm"} It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine separate experimental parameters of Hunter to the already combined invention of Hunter and Cusumano because Hunter further teaches these param e ters may be used in flowthrough mode (compatible with the combined embodiment), under conditions where the multimers bind strongly to the column, while monomeric product passes through the column with little or no binding, making the obviousness dependent on the solution to be filtered. One of ordinary skill in the art prior to the effective filing date of the claimed invention would be motivated to combine because this embodiment may work more efficiently depending on the solution being purified. Given that the applicant claims a broad range of solution and solute components and concentrations, one of reasonable skill in the art would make the determination which embodiment and experimental parameters of Hunter to use, to create the most efficient process. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT CONNOR J ROTONDI whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-2058 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8:00am-4:30pm . 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, FILLIN "SPE Name?" \* MERGEFORMAT Bobby Ramdhanie can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 270-3240 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /CONNOR J ROTONDI/ Examiner, Art Unit 1779 /Bobby Ramdhanie/ Supervisory Patent Examiner, Art Unit 1779