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 .
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). The subject matter of the claims is not disclosed in the specification. The claimed subject matter should have proper antecedent basis in the specification. Appropriate correction is required.
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 1-3, 7-12, 14, 17-18, 20, 22-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because of the following reasons: The claims are drawn to a method, which has 5 active steps, so it is one of the 4 statutory categories. The claim recites judicial exceptions. Selecting a patient is a mental step, requiring only thinking about the patient in order to select him or her. See MPEP 2106.04(a)(2)(III). Advising the patient is a method of organizing human activity. The sub-grouping includes social activities, teaching, and following rules or instructions. The claim does not integrate the judicial exception into a practical application. See MPEP 2106.04(a)(2)(II)(C). The claim does not rely on or use the judicial exception in a further step or process. See 2106.04(d). There are no steps beyond the two judicial exceptions mentioned above, so there cannot possibly be a step which integrates the exception into a practical application. If the patient is one who continues to take the dosage form, but notably whether or not the patient continues the dosage form or not, and how frequently he/she does take it, are completely independent of any judicial exceptions in the claim. The claim does not add significantly more than the exception. There are no additional steps beyond the two judicial exceptions recited in the claim. “An inventive concept ‘cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself.’ … Instead, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966). MPEP 2106.05, second paragraph.
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 1-3, 7-12, 14, 17-18, 20, 22-25 are rejected under 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. There is no description in the specification of a “method of manufacturing a biological therapy, the method comprising: detecting a level of a molecular attribute of the biological therapy in a formulation at one or more timepoints under storage conditions; determining a rate of change of the molecular attribute under the storage conditions; obtaining data on in vivo safety and/or efficacy of the biological therapy for subjects that have received an administration of the biological therapy; estimating a level of molecular attribute exposure received by the subjects at the time of said administration, based on (i) the rate of change of the molecular attribute during storage of the biological therapy in the formulation and (ii) a duration that the biological therapy in the formulation was under the storage conditions prior to said administration; determining a presence or absence of a correlation between the estimated level of molecular attribute exposure and the safety and/or efficacy data for the biological therapy; and if the correlation is absent, manufacturing production lots of the biological therapy comprising the molecular attribute at or below a specified permissible level of the molecular attribute based on the estimated level of molecule attribute exposure,“ according to claim 1, including the meaning of the terms used in the claim and there is no description of how to carry out the method. Further, there is no description in the specification of claims 2-3, 7-12, 14, 17-18, 20, and 22-25, including the meaning of the terms recited in the claims and no description of how to carry out the claimed method.
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 1-3, 7-12, 14, 17-18, 20, 22-25 are rejected under 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 claim 1, it’s unclear what “manufacturing a biological therapy” means, as “biological therapy” has many, non-overlapping meanings within the art (as an example, a biological therapy may include administration of medications, but the term biolgocial therapy may also include exercise, and further may also include psychological counseling, such as by a psyciatrsti. It’s therefore unclaer what bologicla therapy is manufactured by the invention. The term is further unclear because the preamble states “a method of manufacturing a biological therapy,” but no biological therapy is actually produced by the claimed steps. In claim 3, the language “a level of attribute exposure at end-of-shelf that is less than or equal to 90-100%” is unclear as it’s unclear what level of attribute exposure at end-of-shelf means. Further, it’s unclear if a value being less than 90-100% means being less than 90%, or if it means the value may be less than any member of the range, i.e. 90%, 91%... 100%.” Wherever the term “high” (such as “high molecular weight”) and “low” (such as “low molecrul weight) appears in the claims, it is considered indefinite because the claim and the application does not recite what requisite degree is required to constitute “high” and/or “low.” The term “such as” wherever it appears in the claims is indefinite as it’s unclear if the recitation following this phrase are positive claim limitations or merely exemplary. The recitation “an adverse event time course” in claim 18 is indefinite because it’s not clear what constitutes “an adverse event time course.” Further regarding claim 24, it’s unclear if the recitations following “such as” are part of the claimed invention or are merely exemplary, and further unclear why (“such as…” is in parantheses. It’s further unclear what “a nanoparticle/visible/micron-sized resonance mass” is, as this is not a term of art, and how wone could choose between a resonance mass (which refers to mass) and “Brownian motion” (which refers to motion). As a “particle method” is not a term of art, it’s unclear what a “particle method” is. Further regarding claim 25, it’s unclear in what way a Bayseian estimation is comprised by determining a presence or absence of a correlation between the estimated level of molecular attribute exposure and the safety and/or efficacy data for biological therapies.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-3, 7-12, 14, 17-18, 20, 22-25 are rejected under 35 U.S.C. 103 as being unpatentable over Wurth (Quality by Design Aproaches to Formulation Robustness-An Antibody case Study, Journal of Pharmaceutical Sciences, 105(5), May 2016, 1667-1675; IDS filed 6/13/2023) in view of Goetze (Assessingi monoclonal antibody product quality attribute criticality through clinical studies, mAbs,vol 2(5), 2010, 500-507 (IDS filed 6/13/2023). Wurth teaches a method of early stage identification of critical quality attributes (CQAs), and criteria of critical quality attributes (AC-CQAs) and statistical analysis of real-time data to establish a model for predicting shelf-life of mAb formulations, said method takes into account the variation overtime of said CQAs (see p. 1-2, 8 and material & methods). D4 discloses a method based on risk ranking and filtering for identfying CQAs of formulations of mAbs (see p. 293-294, 298-301). In the D5 the risk ranking and filtering approach is used to set a strategy for attribute testing for ensuring that the CQA target ranges that are set on the basis of their potential impact on efficacy, safety and immunogenicity are met during the whole shelf-life of the mAb formulation (see p. 319-322).
The manufacture method of claim 1 differs from the teaching of Wurth in that it comprises (A) determining a rate of change of a molecular attribute under storage conditions and obtaining data on in vivo safety and/or efficacy of the biological therapy for subjects that have received an administration of the biological therapy; (B) estimating a level of molecular attribute exposure received by the subjects at the time of said administration, based on (B1) the rate of change of the molecular attribute during storage of the biological therapy in the formulation and (B2) a duration that the biological therapy in the formulation was under the storage conditions prior to said administration; (C) determining a presence or absence of a correlation between the estimated level of molecular attribute exposure and the safety and/or efficacy data for the biological therapy, wherein the presence/absence of correlation is used to determine the level of quality attribute in the product.
However, Goetze teaches the importance to assess through clinical studies CQAs of mAbs at an early stage within the context of QbD to be able to estimate the desired levels of CQAs that are required to obtain the desired effect as regards efficacy and safety taking into account the changes in the CQAs overtime and the differences in the time for "in-vivo" clearance of the mAb.
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to provide a provision of an improved methodology for the manufacture of biological therapies by optimizing storage conditions for the efficacy and safety of biological therapies, by determining a rate of change of a molecular attribute under storage conditions and obtaining data on in vivo safety and/or efficacy of the biological therapy for subjects that have received an administration of the biological therapy with the aim to establish a link between in-vivo effect of the therapy and (real) exposure to a particular quality attribute, thus producing a method of comprising: detecting a level of a molecular attribute of the biological therapy in a formulation at one or more timepoints under storage conditions; determining a rate of change of the molecular attribute under the storage conditions; obtaining data on in vivo safety and/or efficacy of the biological therapy for subjects that have received an administration of the biological therapy; estimating a level of molecular attribute exposure received by the subjects at the time of said administration, based on (i) the rate of change of the molecular attribute during storage of the biological therapy in the formulation and (ii) a duration that the biological therapy in the formulation was under the storage conditions prior to said administration; determining a presence or absence of a correlation between the estimated level of molecular attribute exposure and the safety and/or efficacy data for the biological therapy; and if the correlation is absent, manufacturing production lots of the biological therapy comprising the molecular attribute at or below a specified permissible level of the molecular attribute based on the estimated level of molecule attribute exposure, wherein if the correlation is present, the method further comprises setting a specification for levels of the molecular attribute at the time of manufacture that do not exceed a maximum permissible level of the molecular attribute of the biological therapy, wherein said maximum permissible level of the molecular attribute is based on the highest estimated levels of molecular attribute exposure that are not associated with adverse events and/or inhibition of efficacy of the biological therapy, said manufacturing further comprising rejecting production lots of the biological therapy comprising levels of the molecular attribute exceeding the maximum permissible levels, wherein the specified maximum permissible level of the molecular attribute is calculated to produce a level of attribute exposure at end-of-shelf that is less than or equal to 90-100% of the highest estimated level of molecular attribute exposure that is not associated with adverse events and/or an inhibition of efficacy in subjects.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL W DICKINSON whose telephone number is (571)270-3499. The examiner can normally be reached on M-F 9 AM to 7:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL W DICKINSON/Primary Examiner, Art Unit 1618 5/15/2025
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