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 .
Claim Status
Currently, claims 2-11, 13-14 are pending in the instant application. Claims 1 and 12 have been canceled. Claims 7-10 are withdrawn and claim 14 has been added. This action is written in response to applicant' s correspondence submitted 07/28/2025. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is FINAL.
Claims 2-6, 11, and 14 are under examination.
Withdrawn Rejections
The rejection of claims 2-6, 11, and 13 under 35 USC 102(a)(1) anticipated by Yelensky is withdrawn in view of the amendment to the claims.
The rejection of claims 2-6, 11 and 13 under 35 USC 102(a)(1) anticipated by Rajasagi is withdrawn in view of the amendment to the claims.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
Claim 14 is 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.
The claims are drawn to a method of preparing a subject specific immunogenic composition comprising at least one tumor specific neoantigen that is identified by identifying a match between a sequence and a sequence in a database when they have in common a string of at 8 amino acids to thereby identify a tumor specific neoantigen encoded by a tumor specific frameshift mutation in genes of a subject having cancer. Thus the claims require identifying a tumor specific neoantigen and preparing a specific immunogenic compositions comprising the tumor specific neoantigen.
The specification shows 5 peptides of SEQ ID NO 333 and one peptide of SEQ ID NO 584. The specification asserts that the vaccine contains these peptides, are personalized based on the patient’s tumor genome. The specification teaches the peptides are shipped for vaccination (sese pg. 28). The instant specification does not provide adequate written description of the claimed genus of immunogenic compositions comprising tumor specific neoantigens. The legal standard for sufficiency of a patent’s written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the Applicant had possession at the time of invention the genus of subject specific immunogenic compositions comprising at least one tumor specific neoantigen.
The post filing date art demonstrates the lack of effective immunogenic compositions based on predicted neoantigens. Liu (Signal Transduction and Targeted Therapy, (2024) 9: 175, pp 1-42) teaches certain types of cancer lack effect neoantigens. Liu teaches discovery and validation of neoantigens is time consuming and expression of antigens varies among individuals (see pg. 10). Liu further teaches only a few bioinformatically predicted neoantigens/peptides are recognized by T cells leading to controversy regarding the reliability of the predictions (see neoantigen identification and validation, pg 18). As Liu demonstrates predicted neoantigens need to be screened and validated to be used for immunogenic compositions. Liu further demonstrates that due to individual variability of antigens and the interferences of the immune microenvironment, the efficacy of cancer vaccines targeting enoatniges exhibits inconsistencies (see pg. 22). Here the specification does not provide any assay to determine which of the predicted neoantigens would be a successful immunogenic composition. The specification does not describe a representative number of immunogenic compositions or describe as assay to predictably determine which of the predicted neoantigens would be a reliable immune compositions.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, 1.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicant was in possession of the genus.
The specification does not provide adequate written description of the claimed invention. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the Applicant had possession at the time of invention of the claimed invention, the genus of subject specific immunogenic compositions comprising at least one tumor specific neoantigen comprising a frameshift mutation in genes by identifying a match with a database consisting SEQ ID NO 1-1989,
The Federal Circuit addressed the application of the written description requirement to DNA-related inventions in University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). The court stated that “[a] written description of an invention involving a chemical genus, like a description of a chemical species, requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials.” Id. At 1567, 43 USPQ2d at 1405. The court concluded that “naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.” Id.
The Federal Circuit clarified that a molecule can be adequately described without disclosing its complete structure. See Enzo Biochem, Inc. V. Gen-Probe Inc., 296 F.3d 1316, 63 USPQ2d 1609 (Fed. Cir. 2002). The Enzo court adopted the standard that the written description requirement can be met by “show[ing] that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics ....i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. “ Id. At 1324, 63 USPQ2d at 1613. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. The court in In re Alonso (Fed. Cir. 2008) citing In re Enzo, Enzo, 323 F.3d at 969 stated that For purposes of satisfying the written description requirement, it is not enough merely to disclose a method of making and identifying compounds capable of being used to practice the claimed invention.
It is noted that AbbVie v. Janssen Biotech and Centocor Biologics (Fed. Cir. 2014) confirms a strong Post-Ariad Written Description requirement - especially with regard to genus- species claim situations. In the decision, Judge Lourie focuses particularly on the alleged infringing antibodies and notes that: [While] AbbVie patents need not describe the allegedly infringing [compound] in exact terms . . . [t]he patents must at least describe some species representative of antibodies that are structurally similar to [the accused compound]. Because the patent document lacked any such structural description, the court confirmed that the corresponding claims were invalid under 112(a). In discussing the case, Judge Lourie was clear that one problem here is that the invention was described in terms of its function rather than its structure. Lourie writes: Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed or through disclosure of a functional characteristic of the claimed genus coupled with a known or disclosed non-functional characteristic (structure) that correlates to the function.
In this case, the specification does not describe the genus of subject specific immunogenic compositions comprising tumor specific neoantigens identified by sequence comparison to a database consisting of SEQ ID NO 1-1989 that satisfies either the Lilly or Enzo standards. The specification does not provide a number of examples sufficient so to describe the entire scope of the claims, the predictability of the scope of the claims. The specification merely identifies how to identify compound capable of neoantigen. The specification provides an example of 6 peptides however there is no indication that these 6 peptides are immunogenic compositions. The specification does not provide a description on how to prepare these compositions. Thus, the specification does not provide an adequate written description of the genus. The instant disclosure does not adequately describe the scope of the claimed genus, which encompasses a substantial variety of subgenera. Since the disclosure fails to provide sufficient relevant identifying characteristics, and because the genus is highly variant, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
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 2-6, 14 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. This rejection was previously presented and has been amended to address the amendment to the claims.
Claim 2 recites “when they have in common a string of at least 8”. This recitation renders the claim indefinite. Sequences in common is not an art recognized term to describe the relationship between two nucleic acid sequences. Is it not clear whether in common includes consists, comprises or shares some unstated level of complementarity or identity, or includes some unstated portion of SEQ ID NO 1-147. Does in common mean same sequence, are conservative replacement, same type of amino acid or some percent identify to the amino acid or sequence. Because “in common” has not been clearly defined in the specification and because there is no art recognized definition for this term as it relates to nucleic acid sequences, one of skill in the art cannot determine the metes and bounds of the claimed subject matter.
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 2-6, 11, and 13-14 rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims are directed to abstract idea and law of nature. This judicial exception is not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter. This rejection was previously presented and has been rewritten to address the amendment to the claims.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? Yes, all of the claims are directed to a process and a system.
Step 2A. Is the claim directed to a law of nature, a natural phenomenon or an abstract idea (judicially recognized exception) and does the claim recite additional elements that integrate the judicial exception into a practical application?
Yes, the claims are directed to law of nature/natural phenomenon. Claim 2 recites identifying at least one neoantigen and step (c) recites to thereby identify a tumor specific neoantigen encoded by a tumor-specific frameshift mutation. Claim 11 recites identifying a tumor specific neoantigen and a tumor specific frameshift mutation. Claim 13 recites identifying at least one neoantigen and step (b) recites to thereby identify a tumor specific neoantigen encoded by a tumor-specific frameshift mutation. The relationship of the neoantigen being tumor specific and the frameshift mutation being tumor specific is a natural phenomenon. The recited relationship is a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of natural processes.
The claims also recite the judicial exception of an abstract idea that is in the grouping of mathematical concepts, such as relationships, formula, calculations and/or mental processes. Claim 1 recites the abstract idea of a mental process. Claim 2 recites the step of “comparing” one sequence to a set of sequences in a database, “identifying” a match between sequences to identifying a tumor specific neoantigen encoded by a tumor specific frameshift mutation. Claim 6 recites “comparing”. Claim 11 recites a first and a second database “configured to store information”, a process “configured to perform instructions… to identifying” a match by comparing sequences from the first and second database. Claim 13 recite “identifying at least one neoantigen”, “determining” the presence of absence of a match between a set of sequences…”identifies a tumor specific neoantigen encoded by a tumor specific frameshift mutation”. Neither the specification or the claims set forth limiting definition for identifying, configuring, comparing, determining or identifying and the claims do not set forth how determining is accomplished. The broadest reasonable interpretation of the determining. comparing and identifying step is a step that can be accomplished mentally by evaluating data and critical thinking process wherein one mentally reads information in a database or report regarding expression levels then draws a mental conclusion. Such “determining”, “comparing” and “identifying “thereby encompasses process that may be performed mentally and this is an abstract idea. The step of configuring is encompassed by a mathematical concept and steps able to be performed in the mind.
Additionally with regard to claim 11, the systems includes a processor configured to perform instructions for identifying a match between two databases.
The recitation of database and processor does not negate the mental nature of the limitations because the claim merely uses the processor and database as a tool to perform the mental process.
Having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
The claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
While claim 11 recites a computer the additional elements of using a process and unidentified instructions to identify a match between two databases do not reflect an improvement in the functioning of a computer. The system includes a processes and instructions, generic hardware that nearly every computer will include.
As mentioned above, a claim limitation can integrate a judicial exception by applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. When evaluating this consideration one must the following:
(i) the particularity or generality of the treatment or prophylaxis limitation;
(ii) whether the limitations have more than a nominal or insignificant relationship to the exception; and
(iii) whether the limitations are merely extra solution activity or field of use.
The steps of “identifying” a neoantigen for preparing a subject specific immunogenic composition is not particular i.e., specifically identified so that it does not encompass all applications of the judicial exception. The step of “preparing” a neoantigen is not specific, there is no specific immunogenic composition that is claimed and encompasses all application of the judicial exception. In other words the claims broadly encompass any and all immunogenic compositions and further does not require administering the therapy to the subject. The recitation of a database is a general link between the abstract idea and generic computer. The database can be any kind of file and storing information in files is what every computer does and there is not any additional elements that use the judicial exception with a particular machine. Here the recitation of a database that consists of sequences and use of a computer is generic. The recitation of a database consisting of SEQ ID NO 1-147 is no more than mere instructions to apply the judicial exception on a computer. These limitations can be viewed as nothing more than an attempt to generally link the use of the judicial exception to a technological environment of a computer.
In addition to the judicial exceptions the claims recite identifying a plurality of neoantigens (claim 4), length of neoantigen (claim 5), comparison of subject genome to normal tissue sample (claim 6), and preparing a subject specific immunogenic composition (claim 14). These additional steps/elements are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception and further limit the judicial exception. Preparing a subject specific immunogenic composition is not specific and generically recites any tumor specific neoantigen.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? No.
Herein the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than well-understood, routine, and conventional activities in the art and do not add something “significantly more” so as to render the claims patent-eligible. The step of preparing a subject specific immunogenic composition merely instructs a scientist to use well established, routine and conventional methods to prepare a composition. As address in the instant specification methods of sequence analysis including preparing immunogenic compositions is well known in the art (see pg. 24).
The step of performing complete, targeted, or partial genome, exome, or transcriptome sequence of at least one tumor sample obtained from a subject constitutes a data gathering step required to apply the law of nature/natural phenomenon and abstract idea. The sequences to be detected are part of the judicial exception and thereby the naming of the sequences does not add something “significantly more” to the recited judicial exceptions.
The additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide inventive concept necessary to render the claims patient eligible. There is no combination of elements in these steps that distinguishes it from well-understood, routine and conventional data gathering activity engaged in by scientists prior to applicant’s invention and at the time the application was filed. Many cited prior art references in this record demonstrate that these techniques were conventional at the time of the invention. The dependent claims further limit the abstract idea and do not provide significantly more to the claims outside of the judicial exception. Additionally the system encompasses a processor and instructions that amount to no more than mere instructions to apply the exceptions using a generic computer components. Mere instructions to apply an exception using a generic computer component cannot provide an inventive concept. None of the recitations of the computer processor offer a meaningful limitation beyond generally linking the system to a particular technological environment, that is implementation via computers. The additional elements in the claims other than the abstract idea per se amounts to no more than a recitation of generic computer structure that serves to perform generic computer functions, the instruction to apply the abstract idea using some unspecified, generic computer is not enough to transform the abstract idea into patent eligible invention. Newly added claim 14 amounts to no more than instruction to apply the abstract idea of identifying a neoantigen. Claim 14 does not recite any specific neoantigens and specific immunogenic compositions and encompasses applying the judicial exception.
Response to Amendment
The response traverses the rejection on page 7 of the remarks mailed 07/28/2025. The response asserts the claims have been amended that the invention is significantly more than identifying a naturally occurring frame shift mutation sequence. The response asserts that the invention utilizes a set of databases that are based on a proprietary set of predicted novel open reading frame peptides and therefore provides a novel and inventive tool that simplifies identification of subject specific, tumor associated antigens for preparing of subject specific immunogenic compositions. The response asserts that the invention is significantly more than the identification of naturally occurring sequences. The response asserts that the specific database of predicted pNOps to identify suitable neoantigens on which to base a novel treatment of the subjects tumor. This response has been reviewed but not found persuasive. The database is not considered significantly more than the judicial exception. The database is an additional element but is it not enough to make the claim significantly more than the judicial exception. While the database consists of specific predicted pNOPs, reciting a database is a mere instruction to apply the abstract idea on a generic computer. Here the database is being applied to the step of comparing the sequences to identify a match, both the comparing and identify steps are abstract ideas and the use of a database is mere instruction to apply the judicial exception. Additionally the database is a file and storing information in files is what a computer does and does not provide significantly more that the judicial exceptions. For these reasons and reasons of record the rejection is maintained.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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