DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of group III, claim 13 in the reply filed on 6/10/25, is acknowledged. Claim 13 has been amended to be directed to a method of personalized vaccine design. Claims 19-25 have been added. Claims 19-24 are part of the elected group, now directed to a method of personalized vaccine design. Claim 25 is directed to a personalized vaccine, which is part of non-elected group I and is withdrawn from consideration. Claims 6-12 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to non-elected group II.
Claims 13 and 19-24 are being acted upon.
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the specification, for example, on page 10, as well as in the drawings, disclose sequences encompassed by the definition in CFR 1.831(b).
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
The use trademarks has been noted in this application (e.g. PYTHONTM or DJANGOTM). Each letter of the trademarks should be capitalized wherever it appears and be accompanied by the generic terminology. Although the use of trademarks is 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 trademarks.
The disclosure is objected to because it contains embedded hyperlinks and/or other form of browser-executable code on pg. 5, for example. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP §608.01.
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 13 and 19-24 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 13 is indefinite in the recitation of an “individual/population’s” nucleic acid sequences. It is not clear if the limitation intends to encompass an individual or a population’s nucleic acid sequences, or does the claim refer to an individual population? Claim 13 is also indefinite in the recitation of said individual/population’s nucleic acid sequences “(viral sequences of interest)”. Specifically, it is not clear whether the parenthetical recitation of viral sequences of interest is merely exemplary, or a required claim element. Additionally, it is not clear what is meant by, for example, an individuals “viral sequences”. Do the claims require that the individual is infected with a virus? Is it viral sequences that an individual is susceptible to? The scope of the claimed nucleic acid sequences is unclear and indefinite.
Claim 13 is also indefinite since it recites the steps A) and B) of inputting nucleic acid sequences, translation, sequence alignment and consensus amino acid sequence building, and then recites a step C) of “predicting epitopes”. However, the clam does not specificity which sequence is used for epitope prediction in step C). Is it a consensus sequence built form step B)? Is it any of the nucleic acids sequences translated in step B)? Could it be a different sequence than used in steps A) and B)?
Claim 13 is also indefinite in the recitation of predicting epitopes by NetMHCpan epitope prediction and “ic50 ranking”. Is the ic50 ranking meant to reference a feature of the MetMCHpan algorithm? Does it refer to a separate epitope prediction method? If it is a separate methodology, it is unclear how it relates to the rest of the claim, since the remainder of the claim only requires sorting NetMHCpan results and makes no further mention of ic50 ranking.
Claim 13 is also indefinite in that it lacks antecedent basis for the recitation of “the iNEtMHCpan” in the penultimate line.
The recitation of “c-score” in claim 13 is unclear and indefinite. How is the score calculated and what does it pertain to?
Claims 21 and 23 are indefinite in the recitation that a predicted immune epitope has a peptide affinity for HLA “predicted by excluding protein portions presenting documented immune escape mutations”. The claim depends from claim 13, which recites a step of predicting epitopes by NetMHCpan and ic50 ranking. Does the step of excluding portions occur in the NetMHCpan prediction algorithm? Is it a separate prediction step? Does the claim intend that the prediction epitopes are sorted by excluding protein portions? The metes and bounds of the claims cannot be established.
The same issue exists for claim 22, i.e. it is not clear how the limitation applies to claim 13, from which it depends. The claim depends from claim 13, which recites a step of predicting epitopes by NetMHCpan and ic50 ranking. Is the further step of predicting epitopes which are least likely to mutate into peptides with decreased affinity part of NetMHCpan. Is it performed before or after NetMHCpan prediction, or is it part of the sorting process? Claim 22 is also indefinite in the recitation of a “candidate vaccine’s HLA”. It is not clear what a candidate vaccine HLA would be. Is it a feature of the vaccine itself for example a vaccine comprising an HLA molecule? Or does it refer to a vaccine candidate’s HLA type, for example.
Claim 24 is indefinite since it is not clear if the recited step is part of the epitope prediction, or a parameter used for sorting? For example, is it definite the basis for sorting escape mutants as recited in claim 13? The scope of the claimed method is unclear and indefinite.
Claim 20 is indefinite in the recitation of “HIV/AIDS”. It is unclear whether this would encompass HIV or AIDS, or whether the claim requires HIV and AIDS.
Claim 19 contains the trademark/trade name PYTHON®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. Furthermore, if a trademark or trade name appears in a claim and is not intended as a limitation in the claim, the question of why it is in the claim should be addressed. If its presence in the claim causes confusion as to the scope of the claim, then the claim should be rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. The use of PYTHON® in the present claim renders the claim indefinite, since it appears to describe a particular product, i.e. a platform that is used in the claimed method.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 21-24 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification and the claims as originally filed do not provide support for the invention as now claimed, specifically:
A) A method wherein a predicted immune epitope has a peptide affinity for HLA, predicted by excluding protein portions presenting documented immune escape mutations (Claims 21 and 23)
B) A method wherein the step of predicting epitopes includes predicting epitopes which are least likely to mutate into peptides with decreased affinity for a candidate vaccine’s HLA (Claim 22).
C) A method further comprising a step of calculating an affinity of potential escape mutants based on an amplitude of an affinity of theoretical mutants (Claim 24).
It is noted that applicant has not cited any support for the new limitation in the specification. A review of the specification fails to reveal support for the new limitations.
Regarding A), the specification discloses sorting NetMHCpan results according to “escape mutations”, and also disclosed a filtration step that can occur between NetMHCpan epitope prediction and sorting, wherein candidate epitopes are filtered based on absence of escape mutations (see the drawings, for example). However, this is not the same as the present claims, which encompass a predicted immune epitope that is predicted by “excluding protein portions presenting documented immune escape mutations”. For example, claim 21 is not limited to a filtration step, but is directed to a prediction step. Furthermore, sorting or filtering based on escape mutations or absence of escape mutations is not the same as “excluding protein portions” presenting “documented immune escape mutations”.
Regarding B), at page 31, the specification discloses in Fig. 1 a filtration step that occurs before sorting epitopes predicted from NetMHCpan results, wherein candidate epitopes are filtered based on absence of escape mutations and/or being located in a structurally conserved region of the virus. However, the specification does not disclose a step of “predicting epitopes which are least likely to mutate into peptides with decreased affinity for a candidate vaccine’s HLA”.
Regarding C), at page 3 and in Fig. 1, the specification discloses an affinity robustness step wherein HLA binding affinities of potential mutant versions of predicted epitopes are simulated to estimate the impact of these mutations on HLA affinity. However, this has a different scope than claim 24. For example, claim 24 does not even apply the recited step to an epitope predicted in the claimed method. Furthermore, the specification does not disclose calculating an affinity of potential escape mutants “based on an amplitude of affinity of theoretical mutants”.
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 13 and 19-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a an abstract idea without significantly more. The claim(s) recite(s) steps of nucleic acid translation, sequence alignment, consensus amino acid sequence building, predicting epitopes and sorting epitope prediction results. These judicial exceptions are not integrated into a practical application because they are abstract ideas (mental processes). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
The present claim is directed to a statutory category, i.e. a process, see step 1 of the eligibility analysis MPEP 2106. The next step (step 2A) involves determining whether the claim is directed to a judicial exception. Regarding prong one of step 2A, the recitation of nucleic acid translation, sequence alignment, consensus amino acid sequence building, predicting epitopes and sorting epitope prediction results are mental processes that are performed in the human mind. Although the claims recite that the step are performed by a computer, it is noted that the courts do no distinguish between claims that recite mental process performed by humans and claims that recite mental processes performed by a computer. See MPEP 2106. Claims can recite a mental process even if they are claimed as being performed on a computer, and in the instant case, the claims merely are directed to using a computer as a tool to perform mental processes. For example, a step of translating nucleic acid sequences could be performed in the human mind using the known codons corresponding to each amino acid. Likewise, the step of consensus amino acid sequence building could be performed in the human mind by comparing and aligning different sequences. Similarly, sorting a list of epitopes based on whether they are evolutionarily considered, or have escape mutations could be performed in the human mind by observation and evaluation and are mental processes and abstract ideas. Thus, prong one of step 2A, is yes, the claims recite an abstract idea, i.e. a mental process. Regarding prong two of step 2A, the claims do not recite any additional elements that integrate the judicial exception into a practical application, such as elements that improve the functioning of a computer or other technology, or applying the judicial exception to effect a particular treatment or prophylaxis of disease.
The next step in the analysis is step 2B which analyzes whether a claim amounts to significantly more than the judicial exception. However, any additional limitations in the present claims amount to simply appending well understood routine, conventional activity at a high level of generality. For example, the limitation of a computing device or server is recited at a high level of generality. Nothing in the claims effects a transformation or reduction of a particular article to a different state. Any additional steps, such as predicting NetMHCpan epitopes, represent well understood, routine and conventional activities already known in the industry. See for example, Backert, 2015, Luo, 2015, Wauquier, 2019, and Du, 2017, which teach that NetMHCpan is a well-known algorithm for epitope predication. Furthermore, the limitations of the dependent claims amount to mere data gathering and represent insignificant extra-solution activity.
When the claim is considered as a whole, the steps taken together amount to no more than recognizing the abstract idea itself. Essentially, appending conventional steps specified at a high level of generality to abstract ideas cannot make ideas patent-eligible. Therefore, the claims do not recite any additional elements that amount to significantly more than the judicial exception, and the present claims are not eligible subject matter under 35 U.S.C. 101.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644