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 .
Election/Restrictions
Applicant's reply to the Restriction Requirement, dated May 18, 2026, has been received. By way of this submission, Applicant has elected the species of at least about 5% increase in a percentage of the plurality of cells expressing the one or more chimeric receptors over 48 hours, as compared to control cells; interferon gamma as a species of cytokine, PD-1 as the species of immune checkpoint inhibitor, CD69 at the species of cell activation marker, and Her2 as the species of antigen.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-14, 29-30, 32-34, and 44 are pending in the application and under examination before the Office.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at page 22. 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.
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 1-14, 29-30, 32-34, and 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. The claims recite a natural phenomenon, a method of detecting cellular synapse formation. This judicial exception is not integrated into a practical application because the claimed data gathering steps do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because measuring activation of said first cell is a well-understood, routine, conventional activity in laboratory technique, and therefore insufficient to amount to an inventive concept.
The Supreme Court has explained that the judicial exceptions reflect the Court’s view that abstract ideas, laws of nature, and natural phenomena are "the basic tools of scientific and technological work", and are thus excluded from patentability because "monopolization of those tools through the grant of a patent might tend to impede innovation more than it would tend to promote it." Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 216, 110 USPQ2d 1976, 1980 (2014) (citing Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589, 106 USPQ2d 1972, 1979 (2013)); Diamond v. Chakrabarty, 447 U.S. 303, 309, 206 USPQ 193, 197 (1980); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978); Gottschalk v. Benson, 409 U.S. 63, 67-68, 175 USPQ 673, 675 (1972). See also Bilski v. Kappos, 561 U.S. 593, 601, 95 USPQ2d 1001, 1005-06 (2010) ("The Court’s precedents provide three specific exceptions to § 101's broad patent-eligibility principles: ‘laws of nature, physical phenomena, and abstract ideas’") (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)) and Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012)).
The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it." See, e.g., Benson, supra, at 71–72. Essentially, appending conventional steps, specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible.
In Prometheus, the Court found that "[i]f a law of nature is not patentable, the neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Additionally, "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law". Flook, 437 U. S., at 590.
The Court also summarized their holding by stating "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
The first step under this guidance is determining if the claim is directed to one of the four statutory categories (process, machine, manufacture, or composition of matter). In this case, the claims are a method (process). The second step is determining if the claims recite or involve judicial exception(s), such as laws of nature, natural phenomena, natural products, or an abstract idea. In this case, the claims are drawn to methods of assessing a plurality of cells for use in a cell therapy. This is a natural correlation/observation of a natural phenomenon, the levels of certain activities and suitability of said cells for a therapy, which is a judicial exception. Thus, it must be determined if the claim as a whole recites something significantly more than the judicial exceptions.
The claimed method recites two assessing steps; an assessing of activity and an assessing of suitability which relies upon the first assessing of activity. The assessing of an activity is merely data gathering, observing the activity of the cells by any conventional means known in the art. For example, determining the levels of biomarkers is a similar type of data gathering. Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. The second step of assessing suitability amounts to no more than applying the exception and drawing a conclusion from it, which is a purely mental step, and also does not add significantly more to the claim to create an inventive concept.
The remaining claims further characterize the exception itself, e.g., particular biomarkers to measure in the assessing step. These specifics are also a) directed to the data gathering step and b) routine choices when practicing the well-established assays for detecting cell activity.
Therefore, claims 1-14, 29-30, 32-34, and 44 are patent ineligible.
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 3-6 and 9-12 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims recite preferential nested ranges of narrow and broader range within the same claim. For example, claim 3 recites ranges of "at least about 50%, 60%, 70%, 80%, or 90% viability". Use of a narrow numerical range that falls within a broader range in the same claim may render the claim indefinite when the boundaries of the claim are not discernible. Description of examples and preferences is properly set forth in the specification rather than in a single claim. A narrower range or preferred embodiment may also be set forth in another independent claim or in a dependent claim. If stated in a single claim, examples and preferences lead to confusion over the intended scope of the claim. MPEP 2173.05(c)(I).
For the purpose of claim construction, the most permissive of the ranges is used to compare the claims to the prior art.
Claim 44 is 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.
Claim 44 recites the limitations of a first antigen and a second antigen. There is insufficient antecedent basis for these limitations, as claim 1 only recites "an antigen".
For the purpose of claim construction, a teaching that recites any one antigen of those recited is taken to read on the claim.
Claim 8 is 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.
Claim 8 recites the limitation of "a Cas endonuclease or a modification thereof". It is not clear what is mean by a "modification" of a Cas9 endonuclease. The specification does not offer any definition as to what this modification may be, nor what sorts of modified Cas9 endonucleases are within the scope of the claims.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 29 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 29 broadens parent claim 1 by adding additional types of activity that may be performed when performing the method of claim 1, specifically, chemotaxis and metabolism. These types of activity are not recited in claim 1, and as such, claim 29 broadens the scope of the method of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 9-14, 29-30, 32-34, and 44 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Hauskins (WO2019027850A1).
Hauskins teaches a method for assessing a cell composition, comprising incubating a population of cells under conditions to stimulate a chimeric antigen receptor (CAR)-dependent activity in cells in the input composition, said input composition containing T cells expressing a chimeric antigen receptor (CAR) containing an extracellular antigen-binding domain that specifically binds or recognizes an antigen, and assessing one or more phenotype or activity of one or more cells (para. 0062). Hauskins also teaches that the conditions to stimulate a CAR-dependent activity includes the presence of a binding molecule that specifically binds to the antigen-binding domain of the CAR (para. 0063).
Hauskins further teaches that the activity to be assessed may be activation, exhaustion or differentiation state, and that the phenotype for exhaustion may be assessed by measuring surface expression of PD-1, and the phenotype for activation may be assessed by measuring surface expression of CD25 (para. 0067), which is pertinent to claims 32-34. Hauskins also teaches that the activation marker may be CD69 (para. 0039).
Hauskins further teaches that the binding of the antigen to the chimeric receptor may result in increased exhaustion (para. 0376), which is pertinent to claim 13.
Hauskins further teaches that the activation marker may be interferon-gamma (para. 0360), which is pertinent to claim 30.
Hauskins further teaches assessing cell viability in this manner (para. 0096).
Hauskins further teaches assessing expression of the chimeric receptor in this manner (para. 0072). Hauskins also teaches that this method is useful for selecting or enriching, from a population of cells, cells expressing an antigen receptor containing an antigen-binding domain specifically recognized by the binding molecule (i.e., increasing the percentage of cells expressing the chimeric receptor) (para. 0060-0061).
Hauskins further teaches that contacting the cells with the antigen stimulates proliferation of the cells (para. 0113).
Hauskins further teaches that the antigen may be Her2 (para. 0007), which is pertinent to claim 44.
Hauskins further teaches comparing the phenotype of the cells to those of control cells (para. 0071), and that expansion (i.e., proliferation), enrichment, stimulation, and/or activation may be a 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1-fold, 2-fold, 3-fold, 5-fold, 10-fold, 100-fold increase, as compared to a control (para. 0317).
Hauskins further teaches that this method is useful to identify cell compositions that may have desirable features when administered in vivo, such as a maintained or extended persistence, viability, or activity (para. 0375).
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.
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 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Hauskins as applied to claim 1 above, and further in view of Budde (PLoS One. 2013 Dec 17;8(12):e82742).
The teachings of Hauskins have been described supra. However, Hauskins does not teach an increase in the plurality of cells expressing both a chimeric receptor and a Cas endonuclease.
Budde teaches a cell that co-expresses a CAR and a Cas9 endonuclease (Figure 1). Budde further teaches that cells expressing the CAR also expressed the Cas9 protein, as visualized by activation of a prodrug (Figure 6).
Budde further teaches that the inducible Cas9 is useful as a "suicide switch" to improve the safety of CAR-T cell therapy (page e82742, right column, second paragraph).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Hauskins and Budde to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Hauskins and Budde are concerned with CAR-T cell engineering. As Budde teaches, cells that can express both a CAR and a Cas9 protein were known in the art, and this combination is useful as a safety measure for CAR-T cell therapy. The methods of Hauskins are useful for enriching cells that express a CAR (i.e., increasing the percentage of cells expressing a chimeric receptor). The cells of Budde express both the CAR and the Cas9, as visualized by the Cas9 activity of the cells in response to a prodrug, and since both the CAR and the Cas9 are located on the same vector. The method of Hauskins, when performed on the cells of Budde, would naturally also increase the percentage of cells that express Cas9. One of ordinary skill could perform the method of Hauskins on the cells of Budde to arrive at the claimed invention. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 7:00 to 3:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER JOHANSEN/Examiner, Art Unit 1644
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