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 .
The amended claims filed 12/23/2025 are under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-35) in the reply filed on 12/23/2025 is acknowledged.
It is noted the claims of non-elected Groups II and III have been cancelled.
Priority
The present application is a 371 national stage entry of PCT/US2021/058741 (filed 11/10/2020), which claims benefit of:
US provisional application 63/112,035 (filed 11/10/2020); and
US provisional application 63/112,359 (filed 11/11/2020).
Priority to the ‘359 provisional application is not recognized as it was filed after the PCT application.
The priority to 11/20/2020 is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout 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 § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or on a submitted IDS, they have not been considered.
Specification
The disclosure is objected to because of the following informalities: the priority claim under the “CROSS REFERENCE” heading does not reflect that this application is a 371 national stage entry.
Appropriate correction is required.
The use of terms, such as Libtayo®, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear 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.
Claim Objections
Claim 28 is objected to because of the following informalities: the claim lacks a conjunction between the terms “(TMB)” and “copy”. Appropriate correction is required.
Claim 30 is objected to because of the following informalities: the claim recites “selecting a treatment for the cancer to the subject based on the copy number of chromosome 9 or the portion thereof in (b)” rather than “selecting a treatment for the cancer based on the results of the assay of (b)”. Appropriate correction is required.
Claim 34 is objected to because of the following informalities: the claim recites “the therapy” in lines 2 and 4 presumably in reference to a “checkpoint inhibitor therapy”. It is suggested a single term be consistently used when referring to a particular claim element. Appropriate correction is required.
Claim Interpretation
Regarding any claim language that is “optional” or “optionally” included within the claim, it is noted claim scope is not limited by claim language that makes optional but does not require the elements. MPEP 2111.04.
In claim 1, the “performing an assay” step broadly encompasses using or assaying any part of the “biological sample” and is not limited to the “cells” or the “cell free material derived from the cancer in the subject”.
Claim 3 broadly encompasses “performing an assay to assess a copy number of chromosome 9” because the claim does not specify the “performing an assay” is done to specifically assess a copy number of a portion of chromosome 9.
Claim 5 broadly encompassing “performing an assay to assess a copy number of chromosome 9” because the claim does not specify the “performing an assay” is done to specifically assess a copy number of a portion of chromosome 9.
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 30, 31, 33 and 34 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
The claims are drawn to a method, one of the four statutory classes.
The claim(s) recite(s) “selecting a treatment for the cancer to the subject based on the copy number of chromosome 9 or the portion thereof in (b)”. The step is an abstract as it may be performed purely in the mind by consideration a limited amount data regarding the copy number of chromosome 9 or the portion thereof.
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claimed limitations add insignificant extra-solution activity to the judicial exceptions as obtaining a biological sample and performing an assay are mere data gathering steps.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims encompass the use of suitable methods and materials known in the art (p. 3), including any biopsy technique known in the art to obtain a biological sample (p. 26) and any method capable of determining a DNA copy number can be used and the skilled artisan is aware of and capable of using a number of different platforms for assessing whole genome copy number changes (p. 29).
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, 2, 3, 5, 6, 7, 8, 9, 11, 12, 16, 17, 18, 20, 27, 28, 30, 31, 33 and 34 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.
Claims 1, 2, 3, 5, 6, 7, 8, 9, 11, 12, 16, 17, 18, 20, 27 and 28 broadly encompass “administering a treatment for the cancer to the subject based on the assessment of step (b)”. The claim broadly encompasses administering any treatment for any cancer based on any assessment of a copy number of chromosome 9 or a portion thereof in any biological sample.
The instant specification only describing administering or selecting a treatment in the context of head and neck tumor samples (p. 75-78, in particular 76). The only treatment evaluated was pembrolizumab or nivolumab (p. 76). The only portions of chromosome 9 with copy number variations that were significantly correlated with the patient’s response was the loss of band 9p24, in particular the loss of genes PD-L1, PD-L2 and/or JAK2 (p. 76).
The specification reasonably demonstrates possession of treating a head and neck cancer patient with pembrolizumab or nivolumab based on a loss of band 9p24, in particular the loss of genes PD-L1, PD-L2 and/or JAK2 (p. 76).
This limited species does not demonstrate possession of treating any other type of cancer based on the loss of any portion of chromosome 9. For example, an analysis of band 9p21 by applicant demonstrated it was not significantly correlated with patients response (p. 76). Thus, one would not have found applicant to be in possession of treating a subject based on the use of the copy number of all of chromosome 9 or band 9p21. Similarly, the only genes within the 9p24 band identified as being significant is PD-L1, PD-L2 and/or JAK2. One would not have reasonably expected applicant to be in possession of using any other genes within the 9p24 band along because applicant did not identify them in the specification as being significantly correlated with the response despite assessing “certain genes” (p. 76).
Claims 30, 31, 33 and 34 recite “selecting a treatment for the cancer to the subject based on the copy number of chromosome 9 or a portion thereof in (b)”. The instant specification does not demonstrate possession of the full scope of this step for the reasons outlined above. Based on the guidance in the specification as detailed above, one would not know how to select any and all treatments for a cancer based on the copy number of chromosome 9 or a portion thereof. For example, there is no guidance as to when an EGFR inhibitor should be selected based on the copy number of chromosome 9 or a portion thereof or when radiation therapy should be selected based on the copy number of chromosome 9 or a portion thereof.
Regarding claim 34, the claim depends from claim 33, which requires selecting a treatment comprising a checkpoint inhibitor. Claim 34 encompasses administering chemotherapy. The instant specification does not support “selecting” a treatment comprising a checkpoint inhibitor based on the copy number of chromosome 9 or a portion thereof and administering the patient any treatment other than the checkpoint inhibitor.
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, 2, 3, 5, 6, 7, 8, 9, 11, 12, 16, 17, 18, 20, 27, 28, 31 and 33 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.
Regarding claim 1, the claim recites “derived from the cancer” starting in line 2. It is unclear if the phrase only modifies the “cell free materials” element.
Claims 2, 3, 5, 6, 7, 8, 9, 11, 12, 16, 17, 18, 20, 27 and 28 depend from claim 1 and are rejected for the same reason.
Regarding claim 1, the claim recites “the assessment” in line 6. The recitation lacks proper antecedent basis as no “assessment” is actually made. The claim is also incomplete because while the step of “performing an assay” is done with the intention “to assess a copy number of chromosome 9 or a portion thereof in the biological sample”, the claim does not require an active method step of “assessing” or “making an assessment of the copy number of chromosome 9”.
Claims 2, 3, 5, 6, 7, 8, 9, 11, 12, 16, 17, 18, 20, 27 and 28 depend from claim 1 and are rejected for the same reason.
Regarding claim 2, the claim recites “the assessment” in line 1. The recitation lacks proper antecedent basis as no “assessment” is actually made. The claim is also incomplete because while the step of “performing an assay” is done with the intention “to assess a copy number of chromosome 9 or a portion thereof in the biological sample”, the claim does not require an active method step of “assessing” or “making an assessment of the copy number of chromosome 9”.
Regarding claim 6, the claim recites “PD-L1”, which lacks proper antecedent basis in claim 5. Claim 5 uses “CD274” rather than PD-L1.
Regarding claim 7, the claim recites “the assessment” in line 4. The recitation lacks proper antecedent basis as no “assessment” is actually made. The claim is also incomplete because while the step of “performing an assay” is done with the intention “to assess a copy number of chromosome 9 or a portion thereof in the biological sample”, the claim does not require an active method step of “assessing” or “making an assessment of the copy number of chromosome 9”.
Regarding claim 28, the claim recites “e.g.”, which is equivalent to "for example", and it 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).
Regarding claim 31, the claim recites “useful combination” in line 3. It is unclear what distinguishes a “useful” combination from a combination. The claim does not specify any context for evaluating whether a combination is “useful” or not.
Regarding claim 33, the claim recites “e.g.”, which is equivalent to "for example", and it 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).
Claim Rejections - 35 USC § 112
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.
Claims 8, 9, 16 and 17 are 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 8 sets forth a property of a “loss of copy number of chromosome”. The claim does not recite any additional steps or further limit any element of claim 7. Claim 8 fails to limit the scope of the active method steps of claim 7.
Claim 9 sets forth a property of an “absence of loss of copy number of chromosome”. The claim does not recite any additional steps or further limit any element of claim 7. Claim 9 fails to limit the scope of the active method steps of claim 7.
Claim 16 depends from claim 7, which are requires the administered treatment to include “an immunotherapy”. Claim 16 specifies the administered treatment for the cancer is a treatment that is “different from the immunotherapy”. The plain language of claim 16 is interpreted as requiring administering any treatment that is not “an immunotherapy”, and thus does not require all the elements of claim 16. The claim does not specify the administering “further comprises administering” an treatment that is not an immunotherapy or one that is different than the immunotherapy.
Claim 17 depends from claim 16 and encompasses administering only a chemotherapy. Thus, claim 17 does not require all the elements of claim 7 from which it indirectly depends.
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.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-3, 5-9, 11-12, 18, 20, 27, 28, 30-31, 33 and 34 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Hacohen (WO 2016/100975 A1).
Regarding claims 1, 3, 5, 6, 7, 18 and 20, Hacohen teaches “obtaining a biological sample comprising cells” in the form of a tumor sample (para. 8).
Hacohen teaches “performing an assay” by determining genetic alterations associated with cytolytic activity in the tumor (para. 8), where the genetic alteration is the copy number gain of chromosomal band 9p24.2-p23 (containing PDL1, PDL2) (para. 11). Alternatively, Hacohen teaches determining a genetic alternation in the form of an amplification of a gene selected from PDL-1/CD274 and PDL-2/CD273 (para. 18).
Hacohen teaches administering an immunotherapeutic agent to the subject if genetic alterations that are associated with induction or suppression to cytolytic activity are found in the tumor (para. 8), i.e. the administering of the immunotherapeutic agent is “based on” the results of the determined genetic alteration of the chromosomal band 9p24.2-p23, PDL-1/CD274 and/or PDL-2/CD273.
Regarding claim 2, Hacohen teaches using an array based platform for copy number determinations (para. 411).
Regarding claim 7, Hacohen further teaches predicting a patient will benefit from the immunotherapeutic agent based on a mutation (para. 106), such as copy numbers (para. 91).
Regarding claim 8, the claim does not require any additional active method steps or elements and merely sets forth a property of a “loss of copy number”. This property does not need to be recognized by the prior art (MPEP 2112.II).
Thus, Hacohen anticipates claim 8 for the same reason it anticipates claim 7.
Regarding claim 9, the claim does not require any additional active method steps or elements and merely sets forth a property of a “an absence of loss of copy number”. This property does not need to be recognized by the prior art (MPEP 2112.II).
Thus, Hacohen anticipates claim 9 for the same reason it anticipates claim 7.
Regarding claims 11 and 12, Hacohen teaches the immunotherapeutic agent comprises at least one checkpoint inhibitor (para. 26). Hacohen teaches the checkpoint inhibitor may be an anti-PD1 antibody such as nivolumab (para. 26).
Regarding claims 27 and 28, Hacohen teaches the cancer is head and neck cancer (para. 11).
Regarding claims 30 and 31, Hacohen teaches “obtaining a biological sample comprising cells” in the form of a tumor sample (para. 27).
Hacohen teaches “performing an assay” by determining genetic alterations associated with cytolytic activity in the tumor (para. 27), where the genetic alteration is the copy number gain of chromosomal band 9p24.2-p23 (containing PDL1, PDL2) (para. 30).
Hacohen teaches “selecting a treatment for the cancer” of a subject by selecting the subject for immunotherapy if the genetic alteration associated with induction of cytolytic activity, tumor resistance to cytolytic activity and/or suppression of cytolytic activity is detected in the tumor (para. 27).
Regarding claim 33, Hacohen teaches the immunotherapy comprises administration of a checkpoint inhibitor (para. 28).
Regarding claim 34, Hacohen teaches administering the selected immunotherapy (para. 8).
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.
Claim(s) 16-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hacohen (WO 2016/100975 A1).
Regarding claims 16-17, Hacohen teaches “obtaining a biological sample comprising cells” in the form of a tumor sample (para. 8).
Hacohen teaches “performing an assay” by determining genetic alterations associated with cytolytic activity in the tumor (para. 8), where the genetic alteration is the copy number gain of chromosomal band 9p24.2-p23 (containing PDL1, PDL2) (para. 11). Alternatively, Hacohen teaches determining a genetic alternation in the form of an amplification of a gene selected from PDL-1/CD274 and PDL-2/CD273 (para. 18).
Hacohen teaches administering an immunotherapeutic agent to the subject if genetic alterations that are associated with induction or suppression to cytolytic activity are found in the tumor (para. 8), i.e. the administering of the immunotherapeutic agent is “based on” the results of the determined genetic alteration of the chromosomal band 9p24.2-p23, PDL-1/CD274 and/or PDL-2/CD273.
Hacohen does not teach the subject has a loss of copy number of chromosome 9 or the portion thereof, and administering a treatment that is different from the immunotherapy.
Hacohen teaches treating patients with a gain of chromosomal band 9p24.2-p23 as noted above with an immunotherapeutic agent because the patient is likely to benefit (para. 91 and 106). However, it would have been prima facie obvious to the ordinary artisan that a patient without a gain of gain of chromosomal band 9p24.2-p23 or a loss of chromosomal band 9p24.2-p23, would not benefit from an immunotherapeutic agent. It would have been prima facie obvious to have treated those patients with a combination , such a combination including a chemotherapeutic agent (para. 64).
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Conclusion
No claims allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682