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 .
Information Disclosure Statement
The information disclosure statements (IDSs) were submitted on 11/17/2023 and 06/30/2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections – 35 USC § 112(a)
The following is a quotation of the 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 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 30 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding Claim 30, claim limitation “wherein the method does not utilize high performance liquid chromatography” (emphasis added) lacks the written description requirement. It fails to disclose a specific structure or feature as to “not utilize high performance liquid chromatography” such a way to describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing. (MPEP § 2161.01).
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.
In claims 24 and 27, claim limitation “(iii) adjusting the continuous load volume of the chromatography column to achieve the optimization” renders the claim indefinite, thereby rendering the scope of the claim unascertainable. It is unclear to indicate how and/or at what reference/result the continuous load volume of the chromatography column is adjusted, and/or if the mathematical result to be calculated using Equation 1 is used to adjust the continuous load volume of the chromatography column. Further, it is unclear what the optimization is indicative of, and unclear how and/or at what reference/feature/structure the optimization is achieved.
In claims 30, claim limitation “high performance liquid chromatography” (emphasis added) is relative terminology to render the claim indefinite, thereby rendering the scope of the claim unascertainable. It is unclear to indicate how and/or at what reference the high performance or the high performance liquid is determined. Examiner notes that Background of page 1 in the instant application may present “the standard method to determine protein concentration in a complex feed is to use a high-performance liquid chromatography (HPLC)-based titer assay”.
In claims 34, claim limitation “the system permits processing up to 6 g/L/day of the biologic product” (emphasis added) renders the claim indefinite, thereby rendering the scope of the claim unascertainable. It is unclear to indicate if the system permits process of maintaining the load density to remain within less than 65 g/L of the predetermined, target load density. It is also unclear to indicate and what the “6 g/L/day” is indicative of.
Claims 25-26, 28-34 and 43-44 are also rejected by virtue of each dependency on claim 24 or 27.
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.
The current 35 USC 101 analysis is based on the current guidance (Federal Register vol. 79, No. 241. pp. 74618-74633). The analysis follows several steps. Step 1 determines whether the claim belongs to a valid statutory class. Step 2A prong 1 identifies whether an abstract idea is claimed. Step 2A prong 2 determines whether any abstract idea is integrated into a practical application. If the abstract idea is integrated into a practical application the claim is patent eligible under 35 USC 101. Last, step 2B determines whether the claims contain something significantly more than the abstract idea. In most cases the existence of a practical application predicates the existence of an additional element that is significantly more.
The 35 USC 101 analysis between each element of claims and its combination is presented in the table below
Claim number and elements
Judicial exception (Step 2A Prong one)
Practical application (Step 2A Prong two)/ Significantly more (Step 2B)
Claim 24
Step 1: Yes, statutory class
Step 2A Prong two: No / Step 2B: No
A method for optimizing continuous chromatography in a system of continuous production of a biologic product, comprising
Step2A Prong one: Yes
(i) taking an optical density (OD)
measurement of an eluate from a chromatography column;
“taking an optical density (OD) measurement …” is an insignificant extra-solution activity to collect routine data (i.e., optical density (OD) measurement).
(ii) applying a mathematical formula to the OD measurement, wherein the mathematical formula is
Equation 1:
PNG
media_image1.png
71
264
media_image1.png
Greyscale
abstract idea
math process
“applying a mathematical formula to the OD measurement ~” is a math process performed using mathematical formula.
and (iii) adjusting the continuous load volume of the chromatography column to achieve the optimization.
abstract idea
mental process or mathematical concept
“adjusting the continuous load volume of the chromatography column to achieve the optimization …” is math or mental process based on the collected data.
Claims 24-34 and 43-44 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 24-34 and 43-44 are directed to an abstract idea. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception as addressed below and presented in the above table.
Step 2A: Prong One
Regarding Claim 24, the limitations recited in Claim 24, as drafted, are processes that, under its broadest reasonable interpretation, cover performance of the limitation in the mathematical calculations and/or the mind, as presented in the above table. Nothing in the claim elements precludes the step from practically being performed in the mind and/or the mathematical calculations. For example, “applying a mathematical formula to the OD measurement, wherein the mathematical formula is …” and “adjusting the continuous load volume of the chromatography column to achieve the optimization” in the context of this claim may encompass mathematical calculations and/or inferring the continuous load volume by using mathematical equation 1 based on the collected routine data (i.e., optical density (OD) measurement). (See pages 22-25 of the instant application).
Step 2A: Prong Two
This judicial exception is abstract ideal itself and not integrated into a practical application. In particular, the specification details use of a computer to perform mathematical calculations of “applying a mathematical formula to the OD measurement, wherein the mathematical formula is …” and “adjusting the continuous load volume of the chromatography column to achieve the optimization”. The system is recited at a high-level of generality to merely gather routine data (i.e., optical density (OD) measurement) and to perform a generic computer function related to mathematical calculations of a generic computer component. The limitation of “taking an optical density (OD) measurement of an eluate from a chromatography column” is insignificant extra-solution activity necessary to merely gather data (i.e., optical density (OD) measurement) to be used for performing the abstract idea. See MPEP 2106.05(g). There is no showing of integration into a practical application such as an improvement to the functioning of a computer, or to any other technology or technical field, or use of a particular machine.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The limitation of “taking an optical density (OD) measurement of an eluate from a chromatography column” is an insignificant pre-solution activity to merely gather routine data (the optical density (OD) measurement) to be used for performing the abstract idea. See MPEP 2106.05(g). As discussed above, with respect to integration of the abstract idea into a practical application, using the data processor of the computer to perform “applying a mathematical formula to the OD measurement, wherein the mathematical formula is …” and “adjusting the continuous load volume of the chromatography column to achieve the optimization” amounts to no more than mere instructions to apply the exception using a generic computer component. Mere instructions to apply an exception using a generic computer component cannot provide an inventive concept cannot provide statutory eligibility. Claim 24 is not patent eligible.
Regarding Claims 25-26, 30-34 and 43, the limitations are further directed to an abstract idea, as described in claim 24. In particular, the limitation of “the optimization comprises maintaining load density to remain within a predetermined, target load density or target load density range” in the context of claim 31 may encompass mathematical calculations and/or inferring load density. The limitations of “the predetermined, target load density is less than about 100 g/L”, “the predetermined, target load density is less than about 65 g/L” and “the system permits processing up to 6 g/L/day of the biologic product” in claims 32-34 may encompass mathematical calculations related to the previous mathematical calculations in claim 24. The limitation of “said method is computer implemented” in claim 43 is indicative of field of use in the art and/or high level of generality. For the reasons described above with respect to claim 24-26, 30-34, and 43, the judicial exceptions are not meaningfully integrated into a practical application, or amount to significantly more than the abstract idea.
Claim 27 has similar limitations as of claim 24 above, and it is therefore rejected under the same rationale as of claim 24 above. Claims 28, 29 and 44 has similar limitations respectively as of claims 25, 26 and 43 above, they are not meaningfully integrated into a practical application, or amount to significantly more than the abstract idea. For the reasons described above with respect to claims 27-29 and 44, the judicial exceptions are not meaningfully integrated into a practical application, or amount to significantly more than the abstract idea.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
CHEN et al. (CN 212379272 U) teaches the claimed feature in claims 24 and 27, where a device used for detection of a target protein including a flow cell (10) connected to the outlet of a chromatographic column (20), the flow cell comprising a UV irradiation device (31) and a spectrometer (32) which measure the absorption at the outlet of the column, and determine the target protein concentration in the eluate (the computer-generated translation reads "The protein concentration detection and calculation device (30) detects the concentration of the solution containing the target protein, and calculates the total amount of protein in the solution containing the target protein in real time"), and the device also comprises a protein load control device (40) which is in communication with the detection and calculation device (30), and which controls the load of the chromatography column in accordance with the total amount of protein as calculated by the device (30).
STEFFEN ZOBEL-ROOS et al. ("Process Analytical Approach towards Quality Controlled Process Automation for the Downstream of Protein Mixtures by lnline Concentration Measurements Based on Ultraviolet/Visible Light (UV/VIS) Spectral Analysis", ANTIBODIES, vol. 6, no. 4, 12 December 2017 (2017-12-12), page 24, XP055596772, DOI: 10.3390/antib6040024) teaches controlling a chromatographic separation of protein by determining the protein concentration in the eluate using a UV detector, and applying appropriate equations which allow a control of the process and a better separation of the products in the load (see abstract), where the concentration is determined by using the measured absorbance value and applying the known extinction coefficient (see D2 page 3, equations (1) and (2)).
KIM et al. (US 20220081476 A1) teaches the column chromatography purification method of a biomolecule may be established and optimized rapidly and at low cost, in a manner to develop an optimal column chromatography process within appropriate cost and time ranges on an industrial scale, where, meanwhile, economic feasibility and device-related limitations (e.g., the use of as few kinds of buffers as possible, the necessity of minimum amounts or volumes of the buffers and chromatography materials, the necessity of maintaining a product-containing fraction volume as small as possible, and the necessity of minimum process time and wastewater volume) also need to be optimized in each step of the process, and where the cell concentration in the culture broth was obtained by measuring optical density at 600 nm. 1 mL of the culture broth was diluted with distilled water to have OD.sub.600=0.2 to 0.5, and an optical density (OD.sub.600) was measured.
Sun (US 8350013 B2) teaches optimize buffer conditions for Protein A column chromatography, where a method for reducing turbidity and impurities in an eluate comprising a product, the method comprising: (a) providing a load fluid comprising a product and one or more impurities, wherein the product is an Fc-containing monoclonal antibody; (b) contacting the load fluid with a medium, wherein the medium is a Protein A chromatography column.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BYUNG RO LEE whose telephone number is (571)272-3707. The examiner can normally be reached on Monday-Friday 8:30am-4:00pm.
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, Lee Rodak can be reached on (571) 270-5628. The fax phone number for the organization where this application or proceeding is assigned is 571-273-2555.
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 https://ppair-my.uspto.gov/pair/PrivatePair. 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.
/BYUNG RO LEE/Examiner, Art Unit 2858
/LEE E RODAK/Supervisory Patent Examiner, Art Unit 2858
Prosecution Insights