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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1 and 3-7) in the reply filed on 06/18/2026 is acknowledged.
Claim 2 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/18/2026.
Priority
The present application is a National Stage entry of International application PCT/US2023/012830 filed 02/10/2023, which claims the benefit of Provisional US application 63309078 filed 02/11/2022.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 08/09/2024, in the matter of Application N° 18/837,265. Said documents have been entered on the record. The Examiner further acknowledges the following:
Claims 1-7 are pending.
Claim 2 is withdrawn from consideration as directed to non-elected inventions.
Claims 1 and 3-7 are presented for examination and rejected as set forth below.
Claim Objections
Claims 3-7 are objected to because of the following informalities: Claims 3-7 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim. For example, claim 7 could depend from claims 1, 3, 4, 5, or 6, which is improper (i.e., although because claim 2 is withdrawn, claim 3 is considered to depend from claim 1). A multiple dependent claim shall not serve as a basis for any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits (i.e., there is a presumption of the dependent claims 3-7, such that each individually depend from claim 1). Appropriate correction is required.
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 and 3-7 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.
Claim 1 (see also claim 2) recites exemplary language such as “e.g.” (i.e., for example) that is indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP 2173.05(d). For examination purposes, the examples provided by the exemplary language are not considered limitations of the claim, and the broadest reasonable interpretation is used.
All claims that depend from claim 1 are additionally rejected.
Claims 4-7 recite “exomes” in which there is insufficient antecedent basis provided, and also exome is a term of the Art that is considered a part of DNA that makes proteins. The Examiner will examine the claims such that this term is a misspelled version of “exosomes” and/or focus on the “exosomes” of claim 4 that are defined as “exomes”.
Claim 4 recites “derived” which is indefinite because it is unclear how far one can deviate from the listed parent compounds/mixtures (i.e., the term “derived” itself does not provide structure, and a PHOSITA could understand this term to mean synthetic chemical derivatization of the instant synthetic and/or natural exosomes, in which there are an indefinite number of ways to derivatize) and yet still remain within the metes and bounds of the invention claimed. For example, it is unclear in what context the term “derived” modifies the exosome, where “derived” could optionally mean originate, chemically-modified, or some other method of procurement that may affect the nature of exosomes (and a suitable explanation of “derived” was not identified in the Specification). Therefore, derived is presumed to mean “originate” or some similar term in the examination of the claims. However, it is difficult to envision “synthetic” exosomes merely originating from a patient without some synthetic chemical processing step.
Claim 7 is indefinite because the phrase discussion Human Papilloma Virus (HPV) of “the HPV-negative cancers behave more like HPV-positive cancers” is subjective and open to indefinite interpretation (i.e., it is unclear the specific behavioral traits which define an HPV-negative cancer vs. an HPV-positive cancer, that is consistent across all HPV-negative and HPV-positive cancer types, which is a group that is inherently heterogenous). Thus, this phrase is disregarded, and the claim is interpreted only within the framework of the active step, describing “HPV-associated exomes are in contact with HPV-negative cancer cells”. Further note that the breadth of HPV-negative cancer cells is broad, in consideration of all known cancer subtypes, that have no association with HPV.
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.
Claims 1 and 3-7 are rejected under 35 U.S.C. 103 as being unpatentable over Hofmann (Int. J. Mol. Sci. 2020).
Applicant’s claims are directed to a method of preventing treatment resistance in non-HPV-associated cancer comprising administering a pharmaceutical composition comprising HPV- associated DNA (e.g., HPV-associated exosomes), wherein the pharmaceutical composition comprising HPV-associated DNA (e.g., HPV-associated exosomes) carry HPV DNA to a subject having, suspected of having, being treated for, having previously been treated for, or diagnosed with cancer. Note the “optional” phrase of instant claim 5 (i.e., “surgical drain harboring HPV oncogene DNA”) is not considered required language of the claim, because it is optional, and is not addressed in the action. Furthermore, the phrase “harvested from a biological fluid” of instant claim 5 is not considered to impart any structural weight for the instant “HPV-associated exomes” (i.e., exosomes, see claim 4 and the 112b rejection above) because it merely describes the origin of the exomes/exosomes.
Hofmann teaches methods of treatment of exosomes incorporating viral DNA (abstract), whereby exosomes reveal enhanced therapeutic activity compared to liposome vesicles (pg 5, ‘section 8’). Hoffmann further teaches the therapeutic effect of TEX on cancers in general, including general mechanisms involving immune suppression (Figure 3).
Regarding claims 1 and 3: Hofmann teaches a method of administering HPV tumor-derived exosomes (TEX) (pg 5, Table 1) (which contain HPV-associated DNA, as understood by the Abstract’s description of exosome contents, which contains DNA of the exosome source) for application in improving outcomes in cancer patients with various cancers, including HNSCC (Head and Neck Squamous Cell Carcinoma) (pg 7, ‘section 4’). Hoffman does not limit the beneficial aspect of TEX to only HPV-associated cancer, because the mechanism of Figure 3 (see below) applies to HNSCC generally (abstract) (which, for example, is characterized as either HPV(+) or HPV(-) (reads on instant claim 3), as shown on pg 7, ‘section 4’), melanoma, colorectal, and/or lung cancer (pg 15, ‘section 8’).
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The method outcome (i.e., of the active step of applying the pharmaceutical composition of instant claim 1) of the prevention of treatment resistance is an expected outcome, because Hofmann teaches that exosomes as therapeutic vesicles that are useful for recurrent HNSCC and/or can prevent chemoresistance (pg 15, ‘section 8’).
Regarding claim 4: Hofmann teaches that HPV is readily prevalent in the oropharynx in evaluation of HNSCC (pg 7, ‘section 4’). Furthermore, human papillomavirus is associated with oropharyngeal cancer (pg 19, reference 63). Thus, extracting the HPV(+) and HPV(-) exosomes such as those found in Table 1, from HPV-positive oropharyngeal cancer patients (pg 2-3, ‘section 2’, and pg 7, 8, and 11) is obvious.
Regarding claim 5: Hofmann teaches exosomes are found in biological fluids (pg 15, ‘section 8’). Thus, extracting the HPV(+) and HPV(-) exosomes such as those found in Table 1, from a biological fluid is obvious. Furthermore, Hofmann teaches exosomes isolated from plasma of patients (pg 2-3, ‘section 2’, and pg 7, 8, and 11). The “optional” phrase of instant claim 5 (i.e., “surgical drain harboring HPV oncogene DNA”) is not considered required language of the claim, because it is optional, and is not addressed in the action.
Regarding claims 6-7: The active steps of the method are described above (i.e., “in contact”). The method outcome of the uptake of an HPV-associated exosome by an HPV-negative head and neck cancer is an expected outcome, based on the mechanism of exosomes on cancers (i.e., contact then leads to immune suppressive and tumor progressive downstream effects that would change the “behavior” of the cancer progression, which requires being “taken up”) that Hofmann provides in Figure 3 (pg 9). The indefiniteness of the “behave” term of claim 7 is addressed in the 112(b) section. Note that exosomes have immune suppression and tumor progressive effects, according to Figure 3 (pg 9).
Thus, the instant method claimed appears to be little more than the rearrangement of known process steps according to their known utility taught from within a single prior art reference, teaching the desirability of selecting the process steps, and obvious thereby, that the process of the instant invention is obvious. It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Thus, the combination of art-known process steps (i.e., administering HPV-associated exosomes) according to their disclosed beneficial properties (i.e., immune suppressant and/or tumor progressive in specific cancers) with the resultant product nothing more than one would expect from the disclosed process steps (i.e., favorable treatment of cancer, including preventing treatment resistance, and/or alteration of tumor environment).
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAJAN PRAGANI whose telephone number is (703)756-5319. The examiner can normally be reached 7a-5p EST (M-Th).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached on 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/R.P./Examiner, Art Unit 1614 08/06/2026
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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