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 .
DETAILED ACTION
Claim Status
1. Claims 1-18 are pending and under consideration.
Priority
2. The instant application has a priority date of September 17, 2021. This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63/245,565, filed September 17, 2021.
Information Disclosure Statement
3. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the Examiner on form PTO-892 or Applicant on PTO-1449 cited the references they have not been considered.
4. The Information disclosure Statement (IDS) filed on 12/19/22 has been considered as to the merits before the First Action.
Specification
5. The use of the term ORBITRAP (i.e. see section 0016), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
6. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See section 0063.
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.
7. Claims 1-18 are 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 pre-AIA the applicant regards as the invention.
A. Claim 1 is vague and indefinite because it is not clear as to what the method will assess. As recited, the method characterizes at least one disulfide bond of a protein of interest. However, the term characterizing is ambiguous as the intended parameter is not clear. The specification appears to define “characterizing in various embodiments”. For examples see section 0075, section 0039 directed to drug development, section 0058 directed to antibody, protein, polypeptide detection, 0060 in protein sequencing, and section 0090 reading on the prevention of disulfide scrambling. Therefore the term “characterizing” is a relative term which renders the claim indefinite. The term “characterizing” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Appropriate correction is required.
B. Regarding claims 3, 8, 9, 12, 13, 15, and 16, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is suggested that the term is omitted from the claims in order to obviate the rejection.
C. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 3, 8, 9, 10, 12, 13, 15, and 16 recite the broad recitation involving units of measurements, and the claim also recites narrow limitations with optionally and/or about in the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
D. Claim 18 contains the trademark/trade name ORBITRAP. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe mass spectrometers and, accordingly, the identification/description is indefinite.
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.
8. Claims 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claims as a whole, the claims are determined to be directed to a law of nature/natural principle and abstract ideas (specific binding complexes formed in nature and mental processes). The claimed invention is directed to a natural phenomenon and/or abstract ideas without significantly more.
The rationale for this determination is explained below:
A claim that focuses on the measurement of disulfide bond modifications must also include additional elements or steps to show that the invention has been practically applied, or added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966. To show integration, the additional elements or steps must relate to the natural principle in a significant way to impose a meaningful limit on the claim scope. The analysis turns on whether the claim has added enough to show a practical application. See id. at 1968.
In other words, the claim cannot cover the natural principle itself such that it is effectively standing alone. A bare statement of a naturally occurring correlation, albeit a newly discovered natural correlation or very narrowly confined correlation, would fail this inquiry. See id. at 1965, 1971.
It is not necessary that every recited element or step integrate or relate to the natural principle as long as it is applied in some practical manner.
However, there must be at least one additional element or step that applies, relies on or uses the natural principle so that the claim amounts to significantly more than the natural principle itself. As recited the claims merely require a nonspecific measurement without a wet step.
Along with integration, the additional steps must be sufficient to ensure that the claim amounts to significantly more than the natural principle itself by including one or more elements or steps that limit the scope of the claim and do more than generally describe the natural principle with generalized instructions to “apply it.” See id. at 1965,
1968. The additional elements or steps must narrow the scope of the claim such that others are not foreclosed from using the natural principle (a basic tool of scientific and technological work) for future innovation.
Elements or steps that are well-understood, purely conventional, and routinely taken by others in order to apply the natural principle, or that only limit the use to a particular technological environment (field-of-use), would not be sufficiently specific. See id. at 1968.
Claim(s) 1 recite(s): “A method for characterizing at least one disulfide bond of a protein of interest, comprising: (a) preparing a peptide digest of a protein of interest, said preparing including: (i) contacting a sample including a protein of interest to cystamine and to at least one denaturation agent to form a denatured protein of interest; (ii) contacting said denatured protein of interest to an alkylation agent to form an alkylated protein of interest; and (iii) contacting said alkylated protein of interest to a digestive enzyme to form a peptide digest; (b) subjecting said peptide digest to analysis using liquid chromatography-mass spectrometry to identify at least one peptide that includes a disulfide bond; and (c) using said at least one identified peptide to characterize at least one disulfide bond of said protein of interest.”
Claim(s) 4 recite(s): “The method of claim 1, further comprising comparing said at least one identified peptide to at least one identified peptide from a control sample including said protein of interest, wherein said control sample is additionally subjected to a protein reduction step.”
The method “characterizes and compares” disulfide in a protein of interest. This “comparison and analysis” reads on mental processes or an abstract idea wherein the detection can be conducted mentally or by a visual signal (without a wet step). Therein, reading on a mental analysis (JE) that is not integrated into a practical application.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because it appears that any presence of a disulfide bond is measured and the measurement does not lead to a tangible result, such as an administration of treatment. In other words, the method only leads to a mental evaluation (i.e. predicting prognosis).
In the instant case the claims are directed to the measurement of naturally occurring proteins/antibodies (disulfide bonds). The disclosure and prior art teaches that adding cystamine to protein/antibodies to prevent disulfide scrambling is known. For example, see Walsh et al. (Chem. Soc. Rev., 2021, 50, 1305—1353, published 12/8/20)
Accordingly, the addition of cysteines through disulfide bonds in proteins is routinely conducted in the prior art.
Further “characterizing” and “comparing/analyzing” data is information regarding a sample or test subject to a control or target data that reads on “An Idea ‘Of Itself’” as when given its broadest reasonable interpretation, such a comparison would read on a mental process that could be performed in the human mind, or by a human using pen and paper. (Determining the presence or a signal could conceivably involve a visual analysis for color indication without any additional hand of man requirement) See July 2015 Update, Quick Reference Guide.
Similar mental processes have been held by the courts to be abstract ideas, e.g., collecting and comparing known information in Classen, or comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC.
The specific information that is being compared the “measurement of cystamine on disulfide bonds in proteins” merely narrows the abstract idea, which does not make the determining/comparison step less abstract and is not sufficient to provide eligibility on its own.
In particular, the “characterizing” step is recited at a high level of generality and is not sufficient to ensure that the claims amount to significantly more than the naturally occurring correlation itself. This is because every application of the correlation would require detecting the cystamine because the “measurement” step does not relate to the natural principle in a significant way to impose a meaningful limit on the claim scope (See claims 1 and 4).
Limitations that are necessary for all practical applications of the natural principle, such that everyone practicing the natural principle would be required to perform those steps or every product embodying that natural principle would be required to include those features, would not be sufficient to confer patent eligibility.
In addition, appending conventional steps, specified at a high level of generality, to a natural principle does not make the claim patent-eligible. Steps that amount to instructions that are well-understood, routine, conventional activity, previously engaged in by those in the field add nothing specific to the natural principle that would render it patent-eligible.
The claims do not include additional elements/steps or a combination of elements/steps that are sufficient to ensure that the claims amount to significantly more than a natural principle itself. This is because (1) the claims would cover every substantial practical application of the correlation and (2) the additional steps recited in the claim were previously taken by those in the field. When the claims are considered as a whole, the steps taken together amount to no more than recognizing the law of nature itself.
The claimed invention is directed to non-statutory subject matter because the claims are drawn to mental analyses that are not integrated into a practical application. Therefore, the claimed invention is not directed to patent eligible subject matter.
Based upon consideration of all of the relevant factors with respect to the claims as a whole, the “characterizing/measuring, comparing and analyzing” steps in claim(s) 1 and 4 is determined to be directed to an abstract idea. The rationale for this determination is explained: Mental determinations of possible effects are not patentable. Simply reciting “characterizing, measuring, comparing, and analyzing” does not provide proper patentable limitations. The judicial exceptions, reading on mental processes have not been integrated into the claimed method.
The active method steps of the present claims; assaying (denaturing/digesting) and determining (mass spectrometry) are conventional, well understood and routine. These steps are the activities that a scientist would have relied upon to achieve the goals of the invention. The steps are interpreted as being drawn to mental steps and/or computer-implemented abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al). In the present claims there are no other active method steps that transform the process into an inventive application of the detected proteins.
The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis from Alice Corp. (also called the Mayo test) for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, Prong 1 determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea enumerated in the 2019 PEG (judicial exceptions) and
Step 2A, Prong 2 determine whether the claim recites additional elements that integrate the exception into a practical application of the exception
If the exception is not integrated into a practical application, then proceed to Step 2B determines whether the claim as a whole, amounts to significantly more than the exception.Analysis of Claims 1 and 4:
I. The present claims are directed to a process so Step 1 is satisfied.
II. The present claims are directed to judicial exceptions? Wherein mental processes are utilized at least in claims 1 and 4 (comparing and characterizing/analyzing proteins). The method is drawn to a natural phenomenon (JE). And this judicial exception includes mental processes - concepts performed in the human mind (including an observation, evaluation, judgment, opinion). Therefore, step 2A Prong 1 and Prong 2 is satisfied.
Claims 1 and 4 are directed to an abstract idea that is not integrated into a practical application (the JE is not integrated into a practical application).
The recited abstract ideas are insufficient to make an otherwise ineligible claim patent eligible without significantly more recited in the claim. The detecting step can be done by merely reviewing the data mentally and mentally making a determination. See Bilski V. Kappos 95 USPQ2d 1001 (2010).
Additionally, see Mayo Collaborative Services v. Prometheus Laboratories Inc. 101 USPQ2d 1961 (2012) at 1965, quoting Gottschalkv. Benson, 409 U.S. 63, 67 [175 USPQ 673] (1972). ("Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.").
Furthermore, the method step of “characterizing” does not actually require an active step but encompasses abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al.).
III. Step 2B, is to determine whether the claim as a whole amount to significantly more than the exception. The active method steps of claims 1 and 4 “denaturing, digesting, and mass spectrometry”. And all of the additional claim elements listed are well-understood, routine, and conventional in this art. The active method steps of the present claims are conventional, well understood and routine.
These steps are the activities that a scientist would have relied upon to achieve the goals of the invention. The steps are interpreted as being drawn to mental steps and/or computer-implemented abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al).
In the present claims there are no other active method steps that transform the process into an inventive application.
In sum, when the relevant factors are analyzed, they weigh against the present claim amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter.
The subject matter which courts have found to be outside of, or exceptions to, the four statutory categories of invention is limited to abstract ideas, laws of nature and physical phenomena. Bilski v. Kappos, 561 U.S. ___, ___, 130 S. Ct. 3218, 3225, 95 USPQ2d 1001, ___ (2010) (citing Diamond v. Chakrabarty, 447 U.S. 303, 309, 206 USPQ 193, 197 (1980)). While this is easily stated, determining whether an applicant is seeking to patent an abstract idea, a law of nature or a physical phenomenon has proven to be challenging.
These three exclusions recognize that subject matter that is not a practical application of an idea, a law of nature or a physical phenomenon is not patentable. See, e.g., Rubber-Tip Pencil Co. v. Howard, 87 U.S. (20 Wall.) 498, 507 (1874) (“idea of itself is not patentable, but a new device by which it may be made practically useful is”);
Mackay Radio & Telegraph Co. v. Radio Corp. of America, 306 U.S. 86, 94, 40 USPQ 199, 202 (1939) (“While a scientific truth, or the mathematical expression of it, is not patentable invention, a novel and useful structure created with the aid of knowledge of scientific truth may be.”).
The courts have also held that a claim may not preempt abstract ideas, laws of nature or physical phenomena; i.e., one may not patent every “substantial practical application” of an abstract idea, law of nature or physical phenomenon.
This is because such a patent would “in practical effect be a patent on the [abstract idea, law of nature or physical phenomenon] itself. ”Gottschalk v. Benson, 409 U.S. 63, 71-72, 175 USPQ 673, 676 (1972).
The concern over preemption was expressed as early as 1852. See Le Roy v. Tatham, 55 U.S. 156, 175 (1852) (“A principle, in the abstract, is a fundamental truth; an original cause; a motive; these cannot be patented, as no one can claim in either of them an exclusive right.”).
Examiners are reminded that 35 U.S.C. 101 is not the sole tool for determining patentability; where a claim encompasses an abstract idea, 35 U.S.C. 112, 35 U.S.C. 102 , and 35 U.S.C. 103 will provide additional tools for ensuring that the claim meets the conditions for patentability. As the Court made clear in Bilski: Accordingly, to the reasons set forth above, claims 1-18 are ineligible. Also, see Alice v. CLS Bank.
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.
9. Claim(s) 1-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Walsh et al. (Chem. Soc. Rev., 2021, 50, 1305—1353, published 12/8/20).
Walsh et al. teaches that antibody–drug conjugates (ADCs) are a class of targeted therapeutics, typically developed for the treatment of cancer.
And harnessing the cell selectivity of monoclonal antibodies (mAbs) and the cytotoxicity of small molecule toxins, malignant cells can be selectively destroyed whilst sparing healthy tissue. Critical to the success of this strategy is a covalent linker between the two therapeutic components, which facilitates the ADC's mechanism of action. This marriage of macromolecular biology and small molecule chemistry is at the heart of the clinical success of ADCs.
Walsh et al. disclose that cysteine residues offer a particularly attractive target for protein bioconjugation due to their low natural abundance and the exceptionally high nucleophilicity of the deprotonated thiolate side chain. For IgG1 modification, naturally occurring cysteine residues can be unmasked by reduction of the four interchain disulfide bonds, revealing up to eight reactive thiol residues. Subsequent reaction with soft electrophiles affords selective bioconjugation at the eight different sites. See figure 5 and section 2.1.
From first generation ADCs that were primarily synthesized via stochastic lysine or cysteine modification, it is clear that significant advances have been made in site-selective antibody modification enabling the widespread synthesis of homogeneous ADCs. Each of these new methodologies has their own advantages and disadvantages. Indeed, there are several instances of contrasting biological results obtained for the same (or highly similar) synthetic strategies with differing antibodies or payloads. Table 1 and Conclusion.
The reference contends that “in addition to the conjugation methodologies, it is paramount that suitable analytical techniques are available to study the reactions and the resulting ADC product. These techniques will also be required to study the in vivo metabolism or biotransformation of these ADCs. Combining techniques such as native mass spectrometry and chromatographic analysis (e.g. HIC or HPLC) will be useful in this regard. It is clear that the technological capability is already in place to achieve this. However, widespread dissemination of the precise methods and set-up parameters is required to further expand their utility”. See page 1342
Walsh et al. teach the components recited in the claims but do not conduct a method wherein each of the steps are presented in a single method. However, combining known reagents in methods previously taught for cystamine bonding is deemed obvious. Absent evidence to the contrary the claimed invention is an obvious design choice of reagents typically employed in the disulfide binding process.
Therefore it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to adjust the reagent combination for antibody-proteins cysteine binding as claimed as a means for optimizing the methods disclosed by Walsh et al.
One skilled in the art would have been motivated to modify the procedures/reagent to maximize stability, efficiency, and accuracy.
10. For reasons aforementioned, no claims are allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lisa Cook whose telephone number is 571-272-0816. The examiner works a flexible schedule but can normally be reached on Monday-Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at telephone number 571-270-3505. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Lisa V. Cook
Patent Examiner
Art Unit 1642
Remsen
571-272-0816
9/30/25
/LISA V COOK/Primary Examiner, Art Unit 1642