Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 6/23/2025 has been entered.
Examiner comment
Please note the examiner of record has changed, it is now Joseph Woitach in Art Unit 1687.
Applicants Amendment
Applicants’ amendment filed 6/23/2025 has been received and entered. Claims 1-46 have been canceled and claims 47-51 have been added.
Claims 47-51 are pending and currently under examination.
Priority
This application filed 6/11/2015 is a 371 National stage filing of PCT/IL2013/051009 filed 12/9/2013 which claims benefit to US Provisional application 61/735569 filed 12/11/2012.
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 15–21, 35–46 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn.
Claims 15–21, 35–46 have been cancelled.
Newly added claims 47-51 doe not recite the limitations previously at issue, and now provide simply measuring free energy between two molecules as a means of comparing and ranking molecules.
In response to Applicants comments, in view of the claim amendments and in review of the specification, it is agreed as acknowledged that “Free energy methods are extensively used by various disciplines and the interest in this field is growing - over 3,500 papers using the most popular free energy computation approaches were published in the last decade, with the publication rate increasing ~17% per year.” (citing ref #4: M.R. Shirts, D.L. Mobley, and J.D. Chodera. Alchemical free energy calculations: Ready for prime time? Annual Reports in Computational Chemistry,3:41-59,2007).
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 48, 50 and 51 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.
This rejection is maintained from the previous Office action as applied to the cancelled claims reciting the limitation of “performing … wet-lab experiments". The originally-filed disclosure does not provide literal or figurative support for these limitations.
Response to Arguments
In the reply filed 6/23/2025, Applicant notes generally support for the claims did not provide any substantial arguments against the rejection under § 112(a)/(pre-AIA ) first paragraph. In review of the specification, the basis of using experiments is acknowledged, however it appears inconsistent the present claims which appears to attempt to replace physical experimentation in analyzing molecular states. Experiment appears four times in the specification, for example page 1: “These will be used to predict likely hood of molecular processes, molecular states etc. which are usually determined by experiments.” and appears to support performing calculations instead of experiments. Further, there are no specific guidance or types of wet lab experiments provided such that one would readily appreciate what is to be performed after free energy calculations are performed.
Amendments providing limitations supported by the specification or a more specific analysis and logic for the support of the limitation would address the basis of the rejection.
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 47-51 are rejected under 35 USC § 101 because the claimed invention is directed to non-statutory subject matter.
Claim Analysis
Newly added claims provide for a method of analysis of free energy between two molecules using a computer, and then for a plurality of analyzed interactions and calculated free energy provides the results in a ranked order based on the free energy values. Independent claims 47 and 49 differ in that claim 47 calculates and assesses ‘binding free energy’ while claim 49 calculates ‘chemical action free energy’. It is noted for the analysis under 101, "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea of "identifying one or more molecules from a pool of potential candidate molecules". More specifically, mathematical concepts recited in the claims include "determining a difference in free energy of a molecular process"; "calculating a free energy of a molecular process" and its constituent steps; "calculating a first difference in free energy …"; "calculating a second difference in free energy …"; and "calculating a main difference between said first free energy difference and said second free energy difference". Such steps of evaluating, analyzing or organizing information recited in the claims include "identifying unshared submolecules among said first molecule and said second molecule"; "selecting at least one molecule from said pool of potential candidate molecules". Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas. The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)).
Dependent claims 48 and 51 also recites the additional, non-abstract element of "performing … wet-lab experiments". Adding the generic technology of physical "wet lab" experiments to the abstract idea imposes no meaningful limits on how the abstract idea itself is performed or implemented. Similarly, adding the abstract idea to the step of performing experiments does not impose any meaningful limits on how those experiments are performed. Hence, this step only generally links the abstract idea to the technological environment of chemistry experiments, rather than integrating the abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(h)). None of the dependent claims recite any additional non-abstract elements; they are all directed to further aspects of the information being analyzed, the manner in which that analysis is performed, or the mathematical operations performed on the information.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a process.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of calculating free energy. The claims requires computing free energy of two molecules for binding or chemical reaction (by means known in the art in view of the teachings of the specification). The judicial exception is a set of instructions for analysis of free energy and found to be Mathematical Concepts for broadly requiring mathematical analysis to determine free energy, and also found to be a Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion) since broadly there is no specific requirements of the claims as to how free energy is calculated and could broadly provide for estimation of values represented by the interaction of two molecules.
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element to which the analysis is applied. This judicial exception requires steps recited at high level of generality and are only stored on a non-transitory, and is not found to be a practical application of the judicial exception as broadly set forth. Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are directed to that abstract idea. Claims that are directed to abstract ideas must be examined further to determine whether the additional elements besides the abstract idea render the claims significantly more than the abstract idea. Claims that are directed to abstract ideas and that raise a concern of preemption of those abstract ideas must be examined to determine what elements, if any, they recite besides the abstract idea, and whether these additional elements constitute inventive concepts that are sufficient to render the claims significantly more than the abstract idea (MPEP 2106.05). As explained above, the mere instructions to implement the abstract idea using a computer are, when considered individually, insufficient to constitute an inventive concept that would render the claims significantly more than an abstract idea (see MPEP 2106.05(f)).
For step 2B of the 101 analysis, each of the independent claims recites additional elements and are found to be the steps of using a computer and/or testing what was calculated in a wet lab experiment. As such, the claims do not provide for any additional element to consider under step 2B. The claims additional elements that are not abstract ideas: that the calculations are performed "by computer operations", which uses a "computer model" to model each molecules. The claims do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)). When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment (i.e. computerization of mathematical calculations). See MPEP 2106.05(a) and 2106.05(h). It is noted that in explaining the Alice framework, the Court wrote that "[i]n cases involving software innovations, [the step one] inquiry often turns on whether the claims focus on the specific asserted improvement in computer capabilities or, instead, on a process that qualifies as an abstract idea for which computers are invoked merely as a tool." The Court further noted that "[s]ince Alice, we have found software inventions to be patent-eligible where they have made non-abstract improvements to existing technological processes and computer technology." Moreover, these improvements must be specific -- "[a]n improved result, without more stated in the claim, is not enough to confer eligibility to an otherwise abstract idea . . . [t]o be patent-eligible, the claims must recite a specific means or method that solves a problem in an existing technological process."
For these reasons, the claims, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
One way to overcome a rejection for non-patent-eligible subject matter is to persuasively argue that the claimed subject matter is not directed to a judicial exception. Another way for the applicants to overcome the rejection is to persuasively argue that the claims contain elements in addition to the judicial exception that either individually or as an ordered combination are not well understood, routine, or conventional. Another way for the applicants to overcome the rejection is to persuasively argue that the claims as a whole result in an improvement to a technology. Persuasive evidence for an improvement to a technology could be a comparison of results of the claimed subject matter with results of the prior art, or arguments based on scientific reasoning that the claimed subject matter inherently results an improvement over the prior art. The applicants should show why the claims require the improvement in all embodiments.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 47-51 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Shirts et al. (2007)(of record).
Shirts et al. review free energy methods were first applied to problems in drug discovery in the early 1990’s, and currently that free energy methods have improved and computational power has continued to grow exponentially. Shirts et al teach that computational chemistry are to provide physical insight by modeling details not easily accessible to experiment and to make predictions in order to aid and guide experiment. More specifically, the review teaches that the ability to rapidly and accurately calculate free energy changes in complex biochemical systems would make possible the computational design of new chemical entities, which has the potential to revolutionize a number of fields and that pharmaceutical chemistry would benefit through virtual high throughput screening, computational lead optimization. Clearly, free energy methods are rapidly becoming standard tools for computational chemists, as computational power grows and methods increase in efficiency, and while methods continue to be standardized, and as understanding of error bounds and limitations continues to grow, free energy calculations will contribute more and more substantially to rational design in biological and other molecular systems. As examples, Shirt et al teach two such systems that have been used as benchmarks by multiple groups for ligand binding are the engineered cavity mutants of T4 lysozyme and FKBP-12 binding protein. The T4 lysozyme system has the advantage of binding relatively small molecules, removing some of the sampling issues, and being relatively small.
Given the review and specific examples, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to use free energy calculations to model molecular interactions. Shirt et al. do not specifically indicate to rank compounds after being analyzed, but provide that the use of free energy can be used to screen potential pharmaceutical compounds but one having ordinary skill in the art would have been motivated to analyze a variety of lead compounds and based on the assessment provide molecules to test. There would have been a reasonable expectation of success given the guidance of Shirt et al. and given the state of the art to analyze the free energy and to use the calculations to assess possible pharmaceutical molecules for future experiments.
Thus, the claimed invention as a whole was clearly prima facie obvious.
Conclusion
No claim is allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
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/Joseph Woitach/Primary Examiner, Art Unit 1687