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 . Herein, "the previous Office action" refers to the Non-Final Rejection of 03/05/2025.
Status of the Claims
Claims 47, 58, 62, and 73-76 are examined; claims 1-46, 48-57, 59-61 and 63-72 are canceled.
Priority
This Application No. 17/050,942 (10/21/2020) is a 371 of PCT/US2019/029540 (04/27/2019) which claims priority from Application No. 62/664,251 (04/29/2018), Application No. 62/671,965 (05/15/2018) and Application No. 62/812,898 (03/01/2019); as reflected in the filing receipt mailed on 08/09/2021. The claims to the benefit of priority are acknowledged. The effective filing date of claims 47, 58, 62, and 73-76 is 10/21/2020.
Withdrawal / Revision of Objections and/or Rejections
In view of the amendment and remarks from 08/08/2025, the following rejections and/or objections are either maintained or newly applied for claims 47, 58, 62, 75 and 76. They constitute the complete set applied to the instant application.
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, 58, 62, 75 and 76 are rejected under 35 USC § 101 because the claimed invention is directed to non-statutory subject matter. "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)).
This rejection is maintained from the previous Office action. The rationale has been revised to address the newly-presented claim limitations.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a method (claims 47, 58, 62, 75 and 76), which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in the claims include "determining percentage vector genome copies per capsid (Vg%)" by "calculating the Vg%" (claims 47 and 75); and "determining the absorbance of the composition” (claims 58 and 75). Thus, the recited terms corresponds to verbal equivalents of mathematical concepts because they constitute actions executed by a group of mathematical steps in a form of a mathematical algorithm; thus mathematical concepts (MPEP 2106.04(a)(2)). A mathematical concept need not be expressed in mathematical symbols, because "words used in a claim operating on data to solve a problem can serve the same purpose as a formula." In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989).
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, and opinions, include: “formulating the isolated rAAV particles" (claim 47); and “using the Vg% to determine the genome copy dosage of the isolated rAAV particles to produce a pharmaceutical unit dosage” (claim 75). The human mind is sufficiently capable of identifying and evaluating information; therefore the recited steps are interpreted as mental processes. Under the BRI, the recited limitations are mental processes because a human mind could decide what particles to include in the composition and evaluate the Vg% to determine the genome copy dosage and the pharmaceutical unit dosage.
Hence, the claims explicitly recite several 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)). [Step 2A Prong One: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Claims 47, 62, 75, and 76 recites additional elements that are not abstract ideas: "isolating rAAV particles …determining the absorbance of a composition comprising the AAV particles at least at 260 nm and 280 nm" (claim 47); "analyzing the composition on an HPLC system with UV detection" (claim 62); “determining the absorbance of a composition comprising the rAAV particles at least at 260 nm and at 280 nm” (claim 75); “producing a pharmaceutical unit dosage comprising the genome copy dosage of the isolated rAAV particles” (claim 75) and "isolating rAAV particles” (claim 76). Adding the generic technology of rAAV absorbance measurement and formulation to the abstract idea imposes no meaningful limits on how the abstract idea itself is performed or implemented; the calculation is performed in exactly the same way regardless of how the absorbance measurements are obtained, and regardless of how the pharmaceutical composition is subsequently formulated. Similarly, adding the abstract idea to the steps of rAAV particle absorbance measurements does not impose any meaningful limits on how the technology of UV absorbance measurement or rAAV formulation operates. UV absorbance is performed in exactly the same manner regardless of whether a practitioner subsequently performs the claimed abstract idea, or some other data processing algorithm, or no additional data processing at all. The pharmaceutical composition is formulated in exactly the same manner regardless of whether the percentage vector genome copies per capsid was determined using the claimed calculation, or some other manner of determining Vg%.
Steps directed to “producing a pharmaceutical unit dosage comprising rAAV particles” (claim 75) do not integrate the abstract idea into a practical application because the calculation does not appear to have any impact on the production step. There is no indication that the calculation of Vg% causes an impact on the producing step in claim 75. Hence, this step only generally links the abstract idea to the technological environment of rAAV analysis and composition formulation, rather than integrating the abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(h)).
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). [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
As explained above, the claims only generally link the abstract idea to the field of rAAV analysis and formulation. Considered individually, this general link is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2106.05(h)).
Furthermore, the specification states that "spectrophotometry is a common method for measuring concentration of products with known extinction coefficients at specific wavelengths and is widely used to determine the protein content for therapeutic proteins" [0004]; that "types of HPLC are well-known in the art" [0068]; and that HPLC separation and UV spectroscopy can be performed using commercially-available equipment [00161–00163].
It is known in the art that the production of pharmaceutical compositions with recombinant adeno-associated virus particles is well-understood, routine and conventional (Clement et. al. “Manufacturing of recombinant adeno-associated viral vectors for clinical trials” Molecular therapy Methods & clinical development 3 (2016) – pg. 1 para. 1). Thus, these elements were well-understood, routine and conventional practices in the art prior to the time of invention. Hence, these elements, when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(d)).
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; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment (i.e., measuring UV absorbance of rAAV compositions, or formulating rAAV compositions). Additionally, they do not improve the technology by allowing the technology to perform a function that it previously was not capable of performing, because the technology of using UV absorbance measurements to quantify rAAV concentration existed prior to the time of invention (e.g., Debelak, et al., Journal of Chromatography B 2000, on IDS of 2 Jan 2024; Sommer, et al., Molecular Therapy 2003, on IDS of 27 Oct 2020; Xie, et al., Journal of Virological Methods 2004, previously cited in 01/31/2024 Final-Rejection). See MPEP 2106.05(a) and 2106.05(h). Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For these reasons, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept. Regarding instant claims 47, 58, 62, 75 and 76 claimed invention does not constitute significantly more than the abstract idea, so the instant claims are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Response to applicant's 20 May 2025 remarks
The Remarks of 08/08/2025 have been fully considered but are not persuasive for the reasons below. The rejection of claims 47, 58, and 62 under 35 U.S.C. § 101 is maintained.
In the Remarks of 08/08/2025, Applicant argues “Amended claim 47 recites formulating the isolated rAAV particles as an active step of the claimed method. A skilled person understands that formulating rAAV particles is not a mental process, as asserted in the Office Action. Office Action, page 5. Rather, it is a manufacturing process during which the composition comprising isolated rAAV particles produced by the purification processes is transformed into a pharmaceutical composition suitable for administration to a human subject. A skilled person understands that formulating a pharmaceutical composition involves, for example, replacing and/or complementing components of the starting composition with one or more pharmaceutically acceptable excipients, such as a buffering agent, a salt and stabilizing agent. Specification, [00214]” (pg. 6 para. 5). As stated in the previous Office action, the steps directed to “formulating” a pharmaceutical composition read on planning the composition’s ingredients involving decisions on what to include; there is no indication that the formulation is impacted by a manufacturing process in anyway way; therefore there is no evident improvement.
In the Remarks of 08/08/2025, Applicant argues “A skilled artisan reading the specification further readily understands the improvements provided by the method according to instant claim 47 over previously available methods for producing a pharmaceutical composition comprising isolated rAAV particles. The claimed method incorporates a process for determining percentage vector genome copies per capsid (V g%) that is faster and cheaper to perform than the previously available methods for determining the ratio of full to empty capsids in isolated rAAV particles, such as Analytical Ultracentrifugation (AUC) and Transmission Electron Microscopy (TEM). Specification, [00107]. Thus, the method according to claim 47 improves the production of a pharmaceutical composition comprising isolated rAAV particles in terms of cost, time and effort. Specification, [0076]” (pg. 7 para. 2). This argument is unpersuasive because ; under the BRI, a human mind could decide what particles to include in the composition and evaluate the Vg% to determine the genome copy dosage and the pharmaceutical unit dosage; which makes the formulating step read on a mental process. For argument matters, even if the formulating step was considered as an additional element, it still would not resolve the 101 rejection because it merely states “based on the Vg%”; and there is no indication of how the pharmaceutical composition itself is improved by the judicial exception. Rather, the improvement is in the judicial exception itself (i.e. the mathematical relationship between Vg& and absorbance). Any improvement to technology as claimed has to be in the additional element and not in the judicial exception (i.e. abstract idea).
In the Remarks of 08/08/2025, Applicant argues “Amended claim 75 recites producing a pharmaceutical unit dosage comprising rAAV particles as an active step of the claimed method. A skilled person understands that producing a pharmaceutical unit dosage of rAA V particles is not a mental process. Rather, it is a manufacturing process comprising transforming a starting composition comprising isolated rAA V particles into a pharmaceutical composition suitable for administration to a human subject and packaging the pharmaceutical composition in individual, pre-measured doses, ready for administration to a patient” (pg. 7 para. 4). The steps directed to “producing a pharmaceutical unit dosage comprising rAAV particles” do not integrate the abstract idea into a practical application because the calculation does not appear to have any impact on the producing step. There is no indication that the calculation of Vg% causes an impact on the producing step in claim 75. Hence, this step only generally links the abstract idea to the technological environment of rAAV analysis and composition formulation, rather than integrating the abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(h)).
In the Remarks of 08/08/2025, Applicant argues “A skilled artisan reading the specification further readily understands the improvements provided by the method according to instant claim 75 over previously available methods for producing a pharmaceutical unit dosage comprising rAA V particles. The claimed method incorporates a process for determining percentage vector genome copies per capsid (V g%) that is faster and cheaper to perform than the previously available methods for determining the ratio of full to empty capsids in isolated rAA V particles, such as Analytical Ultracentrifugation (AUC) and Transmission Electron Microscopy (TEM). Specification, [00107]. Thus, the method according to claim 75 improves the production of a pharmaceutical unit dosage comprising isolated rAAV particles with respect to cost, time and effort. Specification, [0076]. Furthermore, the method according to claim 75 improves the safety and effectiveness of gene therapy by more precisely determining the genome copy dosage of viral particles administered to patients” (pg. 7 para. 5). While the examiner acknowledges that the claims have been amended to recite further elements other than the abstract idea. First, the pharmaceutical composition is formulated in exactly the same manner regardless of whether the percentage vector genome copies per capsid was determined using the claimed calculation, or some other manner of determining Vg%. Second, the calculation does not appear to have any impact on the producing step. There is no indication that the calculation of Vg% causes an impact on the producing step.
In the Remarks of 08/08/2025, Applicant argues “Applicant respectfully submits that the pending claims are patent eligible under 35 U.S.C. § 101 because they are directed to an improved manufacturing process for producing a pharmaceutical composition or pharmaceutical unit dosage comprising recombinant AA V particles wherein the manufacturing process comprises a specific application of mathematical algorithms. See, e.g., XY, LLC v. Trans Ova Genetics, LC, 968 F. 3d 1323 (Fed. Cir. 2020) ("[A]n invention is not rendered ineligible for patent simply because it involves an abstract concept. Indeed, "applications" of abstract concepts to a new and useful end ... remain eligible for patent protection") (internal citations omitted)” (pg. 8 para. 2). The examiner would like to clarify that, in the case of XY, they make a classification, which is improved and then sort the particles based on that classification. Therefore, the improvement in flow cytometry is realized by actually sorting the particles where sorting the particles is an element in addition to the abstract ideas. That is different than the instant claims that are still rejected, which 1) some of the claims (47, 58, and 62) do not actually require the producing step and 2) even if they did, generically recites to make the particles without any indication of what particles are selected in order to realize that improvement.
Finally, the amendments to independent claims 47 and 75 does not render the rejection under 35 U.S.C. § 101 moot as it has been explained in detail in this action .Furthermore, in this instant application, the amendments support existing claim rejections for claims 47, 58, 62, 75 and 76, in which the recited limitations are all addressed, see Claim Rejections above.
Conclusion
Claims 73-74 appear to be free of the art because the limitations directed to an improved manufacturing process for producing a pharmaceutical composition disclosing detailed information about using the Vg% calculation appear to be free from the prior art. The art cited in the previous Office action does not teach or suggest an improved manufacturing process for producing a pharmaceutical composition disclosing detailed information about using the Vg%.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCINI A FONSECA LOPEZ whose telephone number is (571)270-0899. The examiner can normally be reached Monday - Friday 8AM - 5PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached at (571) 272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685