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 .
DETAILED ACTION
Information Disclosure Statement
The IDS filed 3/31/2022 has been considered by the Examiner.
Priority
Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to EP19197306.4 filed 9/13/2019.
Status of Claims
Claims 1-4, 9, 12-24, 26, 27, and 30-38 are under examination.
Claims 5-8, 25, 28 and 29 are cancelled.
Claim Objections
Claims 33-35 drawn to a computer system are objected to because they are recited as depending from claim 31. However claim 31 is drawn to a method and not a computer system. Claims 33-35 will be interpreted as depending from the computer system of claim 32. Appropriate correction is required.
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 1-4, 9, 12-24, 26, 27, and 30-38 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 1-4, 9, 12-24, 26, 27, and 30-31 are drawn to a method, so a process.
Claims 32-35 are drawn to a computer system, so a machine.
Claims 36-38 are drawn to a computer readable medium, so a manufacture.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s):
1. comparing proteinaceous expression products of individual’s non-malignant cells with proteinaceous expression products of said individual’s malignant cells and identifying a set of expression products that are expression products of the malignant cells but not of the non-malignant cells.
This step reads on an information comparison method that can be performed by the human mind and is therefore an abstract idea.
2. identifying at least one malignant cell-derived peptide as having 1) an amino acid sequence which is presented in a proteinaceous expression product but not in any expression product of the non-malignant cells.
This step reads on a process of comparing and analyzing amino acid sequence data that can be performed by the human mind and is therefore an abstract idea.
3. identifying at least one malignant cell-derived peptide as having 1) a high likelihood of being a natural product of antigen processing and an effective binder of at least one MHC molecule when compared to the likelihood of other peptides.
This step reads on analysis of likelihood numerical data which can be performed by the human mind and is therefore an abstract idea.
Step 2A Prong Two: Consideration of Practical Application
The claims do not recite additional elements that integrate the abstract idea into a practical application.
Claim 27 recites a method of therapeutically treating an individual by administering an amount of a personalized immunogenic. However the claim does not recite a particular treatment which integrates the judicial exception of identifying at least one malignant cell-derived peptide. The peptide is not and steps of admixing (claim 24) do not amount to a specific treatment and the claims do not recite what disease is being treated.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
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.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
1. mass spectrometry of peptides eluted from MHC complexes which have been incubated, as in claim 16.
2. admixing a peptide within an immunological adjuvant, as in claims 24 and 26.
3. administering in a boost regime by injection, as in claims 30-31.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because mass spectrometry of peptides, admixing peptides with an immunological adjuvant and administering an injectable treatment by a boost remine, such as a vaccine, are routine, conventional and well understood. The limitations directed to mass spectrometry and treatment of the sample describe a well known method by which the initial peptide data is gathered, which is also pre-solution activity as described in MPEP 2106.05(g). Creating a vaccine based on a peptide is also well known, routine and conventional. Li et al. (Vaccines, vol. 2 2014 pgs. 515-536) evidence teach vaccines made from peptides for induction of immune response.
Other elements of the method include routine computer technology (claims 32-35) including an interface, storage and non-transitory computer readable medium (claims 36-37) which is a recitation of generic computer structure that serves to perform generic computer functions that are well-understood, routine, and conventional activities previously known to the pertinent industry. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112-2nd paragraph
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 1-4, 9, 12-24, 26, 27, and 30-38 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 pre-AIA the applicant regards as the invention.
Claims 1 and 36 recite “a high likelihood,” when compared to the likelihood of other peptides having amino acid sequences present in a proteinaceous expression product in the set. This limitation reciting a “high likelihood” is indefinite because it is a term of degree. The term “high likelihood” does not set forth a metes and bounds for what would be considered “high” even when compared to other peptides having amino acid sequences present in a proteinaceous expression product in the set. How much of a difference to expect in the comparison so as to determine a “high” likelihood is not set forth.
Claim 13 recites “the top 50 likelihood,” such as the top 40, 30, and 25 likelihoods. This limitation is indefinite because the claims do not set forth what “the top 50” likelihoods are the top off, i.e. there claims do not recite how many likelihoods are to be determined and in a potential situation with less than 25 likelihoods determined, there would be no “top likelihood” at all. Clarification is required.
Claims 20 recites “preferably human cells” in step (a) and claim 21 recites “preferably human cells” in step (I). It is unclear what conditions need to be met in order for the condition of “preferably” to be met. It is unclear as to whether the limitation of “human cells” further limits the claims.
Claim 36 (page 12, one line from bottom) recites “likelihood in step b” wherein the claim does not recite a step b. The limitation is therefore unclear.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
10. Claims 1-4, 9, 12-24, 26, 27, and 30-38 are rejected under 35 U.S.C. 103(a) as being unpatentable over Yelensky et al. (US 2017/0199961)
Yelensky et al. teach identifying neoantigens (i.e. proteinaceous expression products) from a tumor of a subject likely to be expressed on a cell surface. Yelensky teach identifying peptides from a neoantigen wherein the neoantigen peptide has alterations relative to the corresponding wild-type peptide (par. 0092 and par. 0044). Yelensky et al. therefore suggest that the neoantigen peptide is compared to the wild-type peptide (i.e. comparing proteinaceous expression products of non-malignant cells with proteinaceous expression products of malignant cells and identifying expression products that are products of malignant cells by not non-malignant cells), as in claim 1, step (a).
Yelensky et al. teach that a neoantigen has a least one alteration that makes it distinct from corresponding wild-type parental antigen, e.g. via mutation in a tumor cell, and can include a polypeptide sequence (i.e. identifying at least one malignant cell derived peptide as having 1) an amino acid sequence corresponding to the proteinaceous expression product but not int eh expression product of the non-malignant cell), as in claim 1.
Yelensky et al. teach inputting sets neoantigen peptide sequences into a model to generate a likelihood that each of the neoantigens is presented by MHC alleles on the tumor cell surface of the subject (i.e. 2) a high likelihood of being a natural product of antigen processing and an effective binder of the at least one MHC molecule), as in claim 1, step (b).
Yelensky et al. do not specifically teach the limitation of identifying high likelihood of binding “when compared to the likelihood of other peptides having amino acid sequences present in a proteinaceous expression product in the set,” as recited in claim 1, step (b).
However, Yelensky teach (par. 0006) that less than 5% of peptides that are predicted to be present using gene expression and MHC binding affinity can be found on the tumor surface MHC, which suggests that non-binding peptide sequences from tumor samples have also been studied.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have compared the binding of identified peptides that have a distinct amino acid present in the malignant set, as taught by Yelensky et al. with the binding of other peptides eluted from tumor samples, as also taught by Yelensky et al. One would be motivated to compare the binding of peptides to MHC in order to develop vaccines that associate with MHC classes of molecules (par. 0219). The combination of teachings of Yelensky would be combination of known elements that would achieve the predictable result of comparing binding of peptides to select the best binders as being those with a “high” likelihood of being a natural product and effective binder.
Regarding claims 2-4, 9, 12-24, 26, 27, and 30-38
Yelensky et al. teach that the neoantigen can include nucleic acid sequence (par. 0040) and that peptides with mutations can be identified by sequencing DNA (par. 0216 and 0183) which suggest identification of DNA sequences of expressed genes from malignant and non-malignant cells, as in claim 2.
Yelensky et al. teach mRNA quantification of tumor cells by mass spectrometry (par. 0039-0040) and general mRNA quantification which suggest non-malignant cells (par. 0321), as in claim 3.
Yelensky et al. teach expression the peptides from mRNA or DNA (par. 0216), as in claim 4.
Yelensky et al. teach peptides from neoantigens compared to the wild-type (par. 0044, 0092) and inputting peptide sequences into presentation model to generate likelihood of presentation by MHC alleles (par. 0092) wherein the peptide presentation models are trained on mass spectrometry (i.e. fragmentation) tumor cell data (par. 0040), as in claim 9, step I.
Yelensky et al. teach a model deep learning presentation model (par. 0093)(i.e. artificial neural network) that predicts peptide presentation on T-cell epitope data (par. 0473); the model presents numerical likelihoods that peptide sequences from the tumor cell are presented by MHC alleles on the tumor cell surface (Yelensky claim 55), as in claim 9, step II.
Yelensky et al. teach generating a numerical likelihood (par. 0097) followed by ranking which suggests that a likelihood of binding would need to be over 50%, as in claims 12-13.
Yelensky et al. teach a dependency score that indicates the likelihood of the MHC allele presenting the corresponding neoantigen (par. 100, 102, and 105-0106)(i.e. for each amino acid, score for the stability of binding between the peptide and MHC molecule), as in claim 14.
Yelensky et al. teach stability prediction of a half-life of 1 hours for the HLA allele (par. 0309 and par. 0324)(i.e. a decay constant for binding), as in claim 15.
Yelensky et al. teach training peptide sequences identified through mass spectrometry on isolated peptides eluted from MHC alleles (par. 0108, 0150) and derived from fresh or frozen samples (par. 0173, 297) suggesting incubation times vary
between samples stored and defined physiological conditions, as in claims 16 and 18-19.
Yelensky et al. teach predicting peptide-MHC binding stability (par. 0122 and 0144), as in claims 17 and 18-19.
Yelensky et al. teach tissue lysates (par. 0295 and 297) and incubating resultant peptides at -20C prior to mass spectrometry analysis (par. 0297), as in claim 20.
Yelensky et al. teach fresh tumor samples which suggests cell lysates prepared at > 4C, as in claim 21, step I.
Yelensky et al. teach predicting stability of neoantigen encoded peptide-MHC complex (par. 0144), as in claim 21, step II.
Yelensky et al. teach cell lines expressing MHC class I or class II alleles, as in claims 22 and 34.
Yelensky et al. teach MHC allele family of molecules being HLA-A, HLA-B HLA-C (par. 0144), as in claim 23.
Yelensky et al. teach identifying peptide mutations by sequencing DNA or RNA protein in tumor cells versus normal cells (par. 0183) and admixing with adjuvants to form a vaccine (par. 0022)(i.e. immunological adjuvant), as in claim 24 and 26.
Yelensky et al. teach treating a subject with a tumor by obtaining a tumor vaccine comprising the set of neoantigens and administering the tumor vaccine to the subject (par. 0128), as in claim 27.
Yelensky et al. teach boosting dosages (par. 0248)(i.e. burst dosage regimes), a in claim 30.
Yelensky et al. teach injections (par. 0244 and 0249), as in claim 31.
Yelensky et al. teach a computerized method for determining a likelihood of a peptide being presented by a MHC molecule.
Yelensky et al. teach a computer for inputting sequences (par. 0057), a storage (par. 0508, 0509), and modules (par. 0510) including modules (i.e. executable code) for training and prediction of the method of claim 1, as in claims 32, 33, 35 and 38.
Claim 36-37 substantially recite the same limitations as instant claims 1-4 and are therefore also taught by Yelensky et al.
E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
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/Anna Skibinsky/
Primary Examiner, AU 1635