DETAILED ACTION
This communication is in response to the after final amendment filed 02/05/26 in which claims 1, 6, 15-17 were amended, and claims 18-20 were newly presented. Claims 1-20 are currently pending.
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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/5/26 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicant’s amendments to claim 1 overcomes the 101 rejection of claim 1 and its dependent claims. Claim 9 remains rejected.
Applicant’s arguments with respect to the art rejections of claim 1 have been fully considered but are moot in light of the new reference used to teach the amended features.
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.
Claim 9 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more, and are analyzed under the Mayo/Prometheus framework as follows.
9. A data processing apparatus [Step 1: apparatus (machine) is a statutory category of invention; Step 2A prong 2/Step 2B: mere instruction to apply exception using generic computer components under MPEP 2106.05(f)] which is configured for generating and storing encrypted fragment data with the method according to claim 1, [see claim 1 analysis above] comprising
a fragmenting device which is configured for [Step 2A prong 2/Step 2B: mere instruction to apply exception using generic computer components under MPEP 2106.05(f)] forming the sequence fragments such that the sections of the series of sequence elements overlap and each sequence element is included in at least two sequence fragments, [Step 2A prong 1: Mental process capable of being performed manually or with the aid of pen and paper using observations, evaluations, judgments, and opinions under MPEP 2106.04(a)(2)(III)]
a coding device which is configured for [Step 2A prong 2/Step 2B: mere instruction to apply exception using generic computer components under MPEP 2106.05(f)] generating the plurality of encrypted fragment data, and [Step 2A prong 1: Mental process capable of being performed manually or with the aid of pen and paper under MPEP 2106.04(a)(2)(III) and/or a mathematical calculation involving a hash function under MPEP 2106.04(a)(2)(I)]
a storage device which is configured for [Step 2A prong 2/Step 2B: mere instruction to apply exception using generic computer components under MPEP 2106.05(f)] storing the encrypted fragment data [Step 2A prong 2: insignificant extra-solution activity under MPEP 2106.05(g); Step 2B: storing information in memory is well understood routine and conventional under MPEP 2106.05(d)].
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.
Claim 9 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Titus, Alexander J., et al. "SIG-DB: Leveraging homomorphic encryption to securely interrogate privately held genomic databases." PLOS Computational Biology 14.9 (2018): e1006454 (“Titus”).
Regarding claim 9, Titus discloses [a] data processing apparatus which is configured for generating and storing encrypted fragment data with the method according to claim 1, comprising
a fragmenting device (p. 12 SIG-DB algorithm testing (“Our algorithm testing was conducted on an NVIDIA Titan X GPU with 64 GB of memory.”)) which is configured for forming the sequence fragments such that the sections of the series of sequence elements overlap and each sequence element is included in at least two sequence fragments, (see Fig. 1 (“In SIG-DB, the k-mers are created using a sliding window of 1 character, as illustrated, with a sequence of length n resulting in `n-k' k-mers.”))
a coding device (p. 12 SIG-DB algorithm testing (“Our algorithm testing was conducted on an NVIDIA Titan X GPU with 64 GB of memory.”)) which is configured for generating the plurality of encrypted fragment data, and (p. 12 (“The initial implementation of SIG-DB uses 48 parallel processes to encrypt the LSH…”))
a storage device which is configured for storing the encrypted fragment data (p. 12 SIG-DB algorithm testing (“Our algorithm testing was conducted on an NVIDIA Titan X GPU with 64 GB of memory.”)).
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 non-obviousness.
Claims 1, 2, 4-8, 10-13, and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Titus in view of MacCarthy (US 2014/0289536 A1; published Sep. 25, 2014).
Regarding claim 1, Titus discloses [a] computer-implemented method for processing genetic data which comprise a series of sequence elements which represent, in each case, a biomolecule, (Abstract (“We present an algorithm for the Secure Interrogation of Genomic DataBases (SIG-DB). The SIG-DB algorithm enables databases of genomic sequences to be searched with an encrypted query sequence without revealing the query sequence to the Database Owner or any of the database sequences to the querier.”)) comprising the steps
forming sequence fragments, wherein each sequence fragment comprises a section of the series of sequence elements with a fragment length of at least two sequence elements, (p. 3 (“There are two major components of the SIG-DB protocol. First, the genomic sequences are converted to a storage efficient data structure. To do so, we chose to use k-mers [sequence fragments]… . The use of k-mers is an established method of breaking up genetic sequences without appreciative data loss; the size of the k-mer can be optimized for a specific application.”); see Fig. 1 (the k-mers fragments are TATCAGA, ATCAGAT, and TCAGATA))
applying a coding function to each of the sequence fragments in order to generate a plurality of encrypted fragment data items, each being associated with one of the sequence fragments, and (p. 3 (“There are two major components of the SIG-DB protocol. First, the genomic sequences are converted to a storage efficient data structure. To do so, we chose to use k-mers and locality sensitive hashing (LSH) [coding function] ...LSHs are also space efficient data structures that store information as either a 1 or 0 and, unlike Bloom filters, force the data to a preset vector size that is smaller than the original data dimensions. For example, the sequence `TATCAGA' would represent a 1 in a separate location within the LSH than `ATCAGAT' (see Fig 1).”)).
Titus does not expressly disclose wherein the coding function is a non-invertible and collision-resistant cryptographic hash function (but see MacCarthy ¶ 119 (“Various system implementations and embodiments, including but not limited to system implementations or embodiments transforming genomic data with cryptographic hash functions, can enable applications that can allow individuals, entities or groups to share genomic data, compare the similarity of genomic data (304), calculate the percent identical genomic data (306), and determine the relatedness or return other measures of the evolutionary or genetic relationship among two or more samples or individuals.”) (cryptographic hash functions are non-invertible and collision resistant)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Titus to incorporate the teachings of MacCarthy to use a cryptographic has function to encode the k-mers, at least because doing so would allow individuals to compare the similarity of genomic data among other things.
Titus further discloses storing the encrypted fragment data in a non-transitory medium to enable secure searching without decryption, (p. 3 (LSH fragments are stored in database of database owner)) wherein
the step of forming the sequence fragments takes place such that the sections of the series of sequence elements overlap and each sequence element is included in at least two sequence fragments (see Fig. 1 (“In SIG-DB, the k-mers are created using a sliding window of 1 character, as illustrated, with a sequence of length n resulting in `n-k' k-mers.”)).
Regarding claim 2, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein
the fragment length of each sequence fragment at least 3 (see Fig. 1 (the k-mers fragments are TATCAGA, ATCAGAT, and TCAGATA)).
Regarding claim 4, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein
all the sequence fragments have the same length (see Fig. 1 (the k-mers fragments are TATCAGA, ATCAGAT, and TCAGATA)).
Regarding claim 5, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein
the sequence fragments form a plurality of fragment groups of sequence fragments, (see Table 1 (k-mer sequences of length 8, 16, and 32)) wherein
the sequence fragments in each fragment group each have the same length, (see Table 1 (all the sequences of a particular K-mer size have the same length))
the sequence fragments of different fragment groups have different lengths, and (see Table 1 (sequences of different K-mer sizes have different lengths))
the forming the sequence fragments takes place such that in each fragment group the sections of the series of sequence elements overlap and each sequence element is included in at least two sequence fragments (see Fig. 1 (K-mer window size is according to the desired length and each successive k-mer sequence overlaps with the next one)).
Regarding claim 6, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein
the encrypted fragment data include hash values (p. 3 (“There are two major components of the SIG-DB protocol. First, the genomic sequences are converted to a storage efficient data structure. To do so, we chose to use k-mers and locality sensitive hashing (LSH) [coding function] ...LSHs are also space efficient data structures that store information as either a 1 or 0 and, unlike Bloom filters, force the data to a preset vector size that is smaller than the original data dimensions. For example, the sequence `TATCAGA' would represent a 1 in a separate location within the LSH than `ATCAGAT' (see Fig 1).”)).
Titus does not expressly disclose genomic sequences includes hash values with a length that amounts to at least 128 bits (but see MacCarthy ¶ 97 (“The method of transforming genomic data input with a cryptographic hash function can further include simultaneously compressing input plaintext sequence information. Implementation incorporating MD5 as a cryptographic hash function can take an arbitrarily long genome sequence (e.g., >>128 bits) and transform that sequence into a 128 bit string.”)).
The rationale for combining Titus with MacCarthy is the same as set forth above.
Regarding claim 7, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein the step of forming the sequence fragments before the application of the coding function comprises
addition, in each case, of a stochastically selected character string to each of the sequence fragments (p. 5 (“Uniformly distributed, random mutations were introduced to query sequences in silico n 5% increments, ranging from 0%-100%.”)).
Regarding claim 8, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein
genetic data from a plurality of individuals are processed, wherein the genetic data of each individual comprise a series of sequence elements which represent, in each case, a biomolecule (p. 3 (“The SIG-DB algorithm is intended for use between two parties: a Querier and a Database Owner who is willing-but-unable to share his genomic data without having a way to protect it. For example, these parties may be businesses wanting to keep their proprietary information protected while collaborating, hospitals collaborating on research while considering HIPAA requirements, or an investigator and a genomic data company.”)).
Regarding claim 10, Titus discloses [a] computer program product which is stored on a non-transitory computer-readable storage medium which when executed by a processor, causes the processor to (p. 12 SIG-DB algorithm testing (“Our algorithm testing was conducted on an NVIDIA Titan X GPU with 64 GB of memory.”)) form the sequence fragments and generate the plurality of encrypted fragment data in a method according to claim 1 (see claim 1 analysis above).
Regarding claim 11, Titus discloses [a] non-transitory computer-readable storage medium on which a computer program product is stored which when executed by a processor cause the processor to (p. 12 SIG-DB algorithm testing (“Our algorithm testing was conducted on an NVIDIA Titan X GPU with 64 GB of memory.”)) form the sequence fragments and generate the plurality of encrypted fragment data in a method according to claim 1 (see claim 1 analysis above).
Regarding claim 12, Titus discloses [a] system comprising: a database stored in a non-transitory memory and configured to store a plurality of searchable, encrypted fragment data which have been generated with a method according to claim 1 (p. 3 (“The SIG-DB algorithm is intended for use between two parties: a Querier and a Database Owner who is willing-but-unable to share his genomic data without having a way to protect it. For example, these parties may be businesses wanting to keep their proprietary information protected while collaborating, hospitals collaborating on research while considering HIPAA requirements, or an investigator and a genomic data company.”)) wherein the system further comprises a processor configured to access and process the encrypted fragment data (p. 12 SIG-DB algorithm testing (“Our algorithm testing was conducted on an NVIDIA Titan X GPU with 64 GB of memory.”)).
Regarding claim 13, Titus discloses [a] method for querying a database containing encrypted fragment data (p. 1 (“We present an algorithm for the Secure Interrogation of Genomic DataBases (SIG-DB). The SIG-DB algorithm enables databases of genomic sequences to be searched with an encrypted query sequence without revealing the query sequence to the Database Owner or any of the database sequences to the Querier.”)) which have been generated and stored with a method according to claim 1, (see claim 1 analysis above) comprising the steps
specifying a search sequence comprising a predetermined series of sequence elements which represent, in each case, a biomolecule, (p. 11 Query preparation (“To build the LSH with the appropriate false positive rate and minimize computational burden, the maximum length of a sequence in the database must be obtained from the Database Owner to serve as a proxy for the number of unique k-mers possible. From this implementation, the LSH is constructed to have a 5:1 ratio of available space to filled locations. For testing purposes, sequences with maximum length of 20,000 base pairs were used, thus LSHs were initialized to have 100,000 available hash locations. For sequences longer than 20,000 base pairs, the first 20,000 bases were used, and sequences shorter than 20,000 base pairs were used in their entirety. Sequence k-mers were hashed into the LSH using the Python hash function.”))
applying the coding function, with which the encrypted fragment data have been generated, on the search sequence for generating an encrypted search sequence, and (p. 11 Query preparation (“Homomorphic encryption was implemented with the Python package phe[19], implementing the Paillier additive homomorphic encryption system (PHE)[12]. Under this system, a public key/private key pair is generated and each element of an LSH is encrypted using the public key. The Paillier cryptosystem is based on integer factorization, and as such our default key size (DEFAULT_SIZE = 3072) is chosen to give a minimum of 128 bits of security.”))
searching for the encrypted search sequence in the stored encrypted fragment data (p. 11 Database searching (“An LSH is created for each database entry using the LSH Constructor, provided by the Querier. The Database Owner executes the comparison between each DB entry LSH and the encrypted Query LSH using the comparison executable provided by the Querier. For each comparison, an encrypted intersection score is calculated by the sum of all the encrypted Query LSH hash locations corresponding to a filled hash entry in the DB entry's LSH. The magnitude of the DB entry LSH is calculated as the sum of hashes in the LSH. The pair {encrypted intersection score, DB entry LSH magnitude} for each entry in the database are then returned to the Querier for evaluation.”)).
Regarding claim 15, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein
the encrypted fragment data are stored in a database (p. 3 (“The SIG-DB algorithm is intended for use between two parties: a Querier and a Database Owner who is willing-but-unable to share his genomic data without having a way to protect it.”)).
Regarding claim 16, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein
a predetermined series of sequence elements comprises a section of genetic material (see Fig. 1 (nucleotide sequence)).
Regarding claim 17, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein
the genetic data represent a nucleotide sequence or an amino acid sequence (see Fig. 1 (nucleotide sequence)).
Regarding claim 18, Titus discloses the invention of claim 9 as discussed above. Titus does not expressly disclose wherein the encrypted fragment data comprise hash values with a length that amounts to at least 128 bits (but see MacCarthy ¶ 97 (“The method of transforming genomic data input with a cryptographic hash function can further include simultaneously compressing input plaintext sequence information. Implementation incorporating MD5 as a cryptographic hash function can take an arbitrarily long genome sequence (e.g., >>128 bits) and transform that sequence into a 128 bit string.”)).
The rationale for combining Titus with MacCarthy is the same as set forth above.
Claims 19 and 20 are apparatus and method claims corresponding to claim 18 and, therefore, are similarly rejected.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Titus and MacCarthy as applied to claim 1 above, and further in view of Zhang, Qingpeng, et al. "These are not the k-mers you are looking for: efficient online k-mer counting using a probabilistic data structure." PloS one 9.7 (2014): e101271 (“Zhang”).
Regarding claim 3, Titus, in view of MacCarthy, discloses the invention of claim 1 as discussed above. Titus further discloses wherein the step of forming the sequence fragments comprises
specifying the fragment length and a start element in the genetic data, and (Fig. 1 (“In SIG-DB, the k-mers are created using a sliding window of 1 character, as illustrated, with a sequence of length n resulting in `n-k' k-mers.”))
providing the sequence fragments, in each case, using the sections of the series of sequence elements with a predetermined fragment length beginning at the start element and at all the subsequent sequence elements (see Fig. 2 (“SIG-DB protocol for (1) hashing sequence into locality sensitive hash (LSH), (2) encrypting and passing LSH,…”)).
Titus does not expressly disclose specifying a start element in the genetic data (but see Zhang 11 Future Conditions (“It is possible to reduce the required memory by dividing k-mer space into multiple partitions and counting k-mers separately for each partition. Partitioning k-mer space into M partitions results in a linear decrease in the number of k-mers under consideration, thus reducing the occupancy by a constant factor M and correspondingly reducing the collision rate. Partitioning k-mer space is a generalization of the systematic prefix filtering approach, where one might first count all k-mers starting with AA, then AC, then AG, AT, CA, etc., which is equivalent to partitioning k-mer space into 16 equal-sized partitions. These partitions can be calculated independently, either across multiple machines or iteratively on a single machine, and the results stored for later comparison or analysis.”)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Titus to incorporate the teachings of Zhang to partition the input sequence and initiate windowing at specific elements, at least because doing so would reduce the memory requirements so that the generated K-mers can be efficiently stored for later comparison or analysis. Zhang 11 (“It is possible to reduce the required memory by dividing k-mer space into multiple partitions and counting k-mers separately for each partition.”).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Titus and MacCarthy as applied to claim 13 above, and further in view of Glick (US 2009/0270277 A1; published Oct. 29, 2009).
Regarding claim 14, Titus, in view of MacCarthy, discloses the invention of claim 13 as discussed above. Titus teaches assessing a similarity between the query and entries in the database in scenarios with a query sequence longer than the database sequences, see p. 12, but Titus does not expressly disclose wherein
the specifying of the search sequence comprises a shortening of an initial search sequence to a search sequence length that is equal to the fragment length of the sequence fragments from which the encrypted fragment data have been generated (but see Glick ¶ 39 (“With a query longer than K bases, the constituent K-mers are examined in increasing order of their frequency of appearance in the subject DNA sequence. For example, a search for the 12-mer AAAACCCCGGGG using K=4 might involve calculating the positions for CCCC, then comparing each CCCC position against the list of positions for GGGG, then comparing each CCCCGGGG position against the list of positions for AAAA, which in this case would be the most common of the three 4-mers. This strategy of starting with the rarest K-mer can significantly accelerate searches because some K-mers are found less frequently than others and therefore result in fewer comparisons. In chromosome 1, the most common 4-mer (AAAA) appears 56 times more often than the rarest 4-mer (CGCG), and the most common 6-mer (TTTTTT) appears 929 times more often than the rarest 6-mer (CGTACG).”)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Titus to incorporate the teachings of Glick to start with the rarest K-mer as the query sequence when the initial query sequence is longer than the longest K-mer used to build the hash sequences in the owner database, at least because doing so would significantly accelerate searching. See Glick ¶ 39.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHAHID KHAN whose telephone number is (571)270-0419. The examiner can normally be reached M-F, 9-5 est.
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/SHAHID K KHAN/Primary Examiner, Art Unit 2146