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 .
Priority
The instant application, filed December 20th, 2023, is a 371 filing of PCT/EP2022/067140, filed June 23rd, 2022, and claims foreign priority benefit to application SE20150815-5, filed June 23rd, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of Claims/Application
The preliminary amendment of December 20th, 2023 is acknowledged. Claims 1-18, filed on December 20th, 2023, are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 20th, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Claim 1, 10, and 18 require the SEQ ID NO: 1 recitation for the amino acid sequence N-terminal-GLGHN.
Claim 7, 12, 16, and 17 require the colon (“:”) after SEQ ID NO. It should be amended to “(SEQ ID NO: 1)”.
In the specification, there are instances where GLGHN is missing a “SEQ ID NO:”. See for example, page 5, lines 18, 23, and 31. Also, page 5, line 2, “SEQ ID NO 1” is missing a colon between “NO” and “1.”
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 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions (i.e. a law of nature, natural phenomenon, and/or an abstract idea) without significantly more. Abstract ideas include mathematical concepts, mental processes, and certain methods of organizing human activity. The rationale for this determination is explained below:
Claims 1-6 are directed towards a method of diagnosing a disease comprising of providing a sample previously isolated from a subject and analyzing the sample for presence of a peptide comprising the amino acid sequence N-terminal-GLGHN in the sample. The claims are directed to a natural phenomenon and an abstract idea (“Step 2A prong 1”) and the judicial exception are not integrated into practical application (Step 2A prong 2”). The natural phenomenon is the presence of the N-terminal-GLGHN in the sample of a subject and the abstract idea is a mental process/human activity to analyze the sample for the presence of the N-terminal-GLGHN peptide in the sample to determine if the subject has the disease.
The claims do not include additional elements that are sufficient to amount to significantly more than just the judicial exception. A claim that focuses on the judicial exceptions can be shown to recite something “significantly more” by reciting a meaningful limitation beyond judicial exceptions. However, in the instant application, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (when considered both individually and as an ordered combination) are limited to well-understood, routine and conventional limitations of measuring the presence of a peptide in a sample of a subject. In this instant application, the peptide is N-terminal-GLGHN in the sample of a subject (“Step 2B”). Well understood, routine and conventional limitation are not enough to qualify for the claimed method as reciting something “significantly more” than the judicial exception (see Part I.B.1. of the interim guidance).
MPEP 2106.05(d)(II) provides a non-limiting list of laboratory techniques recognized by the courts as well understood, routine and/or conventional activity:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Further Applicant’s specification but not in the claims, recites ELISA is well-known in the art of diagnostics (page 9, line 32) using an antibody that would recognize the peptide in a sample.
Further prior art teaches ELISA as a form of diagnostics for a biglycan peptide for diseases. Genovese (Genovese F, Barascuk N, Larsen L, Larsen MR, Nawrocki A, Li Y, Zheng Q, Wang J, Veidal SS, Leeming DJ, Karsdal MA. Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases. Fibrogenesis Tissue Repair. 2013 May 1;6(1):9. doi: 10.1186/1755-1536-6-9. PMID: 23635022; PMCID: PMC3651402) teaches a monoclonal antibody to an amino acid sequence in the biglycan peptide (page 1, abstract and page 2, column 2, “selection of monoclonal antibody for assay development…”) which is used as a diagnostic ELISA assay for a biglycan neo-epitope fragment present in pathological diseases such as fibrosis and rheumatoid arthritis.
Therefore, the claims “simply inform” the natural phenomenon to one performing routine method steps and do not amount to “significantly more” than the judicial exception.
Claim 16 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim recites the peptide N-terminal-GLGHN having a length of from 5 to 20 residues which is a product of nature as recited in MPEP 2106.04(b)(II). Further, the nature based product does not exhibit markedly different characteristics from the naturally occurring counterpart in its natural state (See MPEP 2106.04(c)). In this case, the peptide N-terminal-GLGHN that varies from 5 to 20 residues are not different from the full length sequence of the biglycan that the claimed invention is reciting. Genovese teaches the full biglycan peptide sequence that is conserved in humans and horses
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(page 1, figure 1b and column 2, “The BGM peptide was shown to be unique to biglycan with 100% homology across different species (Homo sapiens, Mus musculus, Rattus norvegicus, Canis lupus familiaris, Equus caballus, Bos Taurus, Ovis aries)”). Therefore, the claimed invention is not markedly different from its natural state.
Furthermore, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are recited (Step 1: Yes, Step 2A: Yes, Step 2B: No).
Claim 12 is rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. As described in claims 1-6, claim 12 recites the method of treating a disease by repeatedly obtaining a sample from the subject and analyzing the sample for the presence of the N-terminal-GLGHN peptide in the samples and “if the level of the peptide in the subject in the sample is above a predetermined level, determining the subject should be treated, where the treatment is resting the subject”. Claim 12 is directed to a natural phenomenon and an abstract idea because the claims recite natural phenomenon (measuring the N-terminal-GLGHN peptide) and an abstract idea (“analyzing the presence of the N-terminal-GLGHN peptide in a sample” and “if the level of the peptide in the subject in the sample is above a predetermined level, determining the subject should be treated, where the treatment is resting the subject” (“Step 2A prong one”) and the judicial exception(s) is/are not integrated into a practical application (“Step 2A prong two”). The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (when considered both individually and as an ordered combination) are limited to well-understood, routine and conventional limitations of measuring the presence of a peptide in a sample of a subject. In this instant application, the peptide is N-terminal-GLGHN in the sample of a subject (“Step 2B”). Well understood, routine and conventional limitation are not enough to qualify for the claimed method as reciting something “significantly more” than the judicial exception (see Part I.B.1. of the interim guidance).
MPEP 2106.05(d)(II) provides a non-limiting list of laboratory techniques recognized by the courts as well understood, routine and/or conventional activity:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017).
Therefore, the claim “simply informs” the natural phenomenon to one performing routine method steps and do not amount to “significantly more” than the judicial exception.
Further, claim 12 recites treatment “if” the subject has a certain level of N-terminal-GLGHN. Claim 12 is readable on subjects who do not receive any treatment “if” they do not meet a certain threshold. Therefore, subjects who do not receive the treatment receive a diagnostic method that is not integrated into a practical application. See MPEP 2111.04(II) for contingent limitations in claims.
Further, the recited step of providing a treatment is “resting the subject” fails to integrate the claim or to add significantly more (Step 2b). This amounts to no more than a suggestion to apply the judicial exceptions of claim 12. See MPEP §2106.05(f).(1). The recitation of claim limitations that attempt to cover any solution to an identified problem with no restriction on how the result is accomplished and no description of the mechanism for accomplishing the result, does not integrate a judicial exception into a practical application or provide significantly more because this type of recitation is equivalent to the words "apply it". See Electric Power Group, LLC v. Alstom, S.A., 830 F.3d 1350, 1356, 119 USPQ2d 1739, 1743-44 (Fed. Cir. 2016); Intellectual Ventures I v. Symantec, 838 F.3d 1307, 1327, 120 USPQ2d 1353, 1366 (Fed. Cir. 2016); Internet Patents Corp. v. Active Network, Inc., 790 F.3d 1343, 1348, 115 USPQ2d 1414, 1417 (Fed. Cir. 2015).
Claim 17 rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim 17 does not fall within at least one of the four categories of patent eligible subject matter because the statement “use of” of an invention without any meaningful steps for that use does not qualify as a process, machine, manufacture or composition of matter. (Step 1 of Subject Eligibility Analysis: NO) (See MPEP 2106.03 (I) and (II)). As explained by the courts, these “four categories together describe the exclusive reach of patentable subject matter. If a claim covers material not found in any of the four statutory categories, that claim falls outside the plainly expressed scope of § 101 even if the subject matter is otherwise new and useful.” In re Nuijten, 500 F.3d 1346, 1354, 84 USPQ2d 1495, 1500 (Fed. Cr. 2007)
Claim 17 also rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, first paragraph. Specifically, because the claimed invention does not set forth any steps involved in the method/ process of using the peptide for production of an antibody, it is unclear what method/ process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
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.
Claims 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 8,623,611 B2, issued January 7th, 2014 (herein referred to as “Pierce”) and in further view of Kram (Kram V, Shainer R, Jani P, Meester JAN, Loeys B, Young MF. Biglycan in the Skeleton. J Histochem Cytochem. 2020 Nov;68(11):747-762. doi: 10.1369/0022155420937371. Epub 2020 Jul 6. PMID: 32623936; PMCID: PMC7649967) and Martig (Martig S, Chen W, Lee PV, Whitton RC. Bone fatigue and its implications for injuries in racehorses. Equine Vet J. 2014 Jul;46(4):408-15. doi: 10.1111/evj.12241. Epub 2014 Apr 1. PMID: 24528139), Koczula (Koczula KM, Gallotta A. Lateral flow assays. Essays Biochem. 2016 Jun 30;60(1):111-20. doi: 10.1042/EBC20150012. PMID: 27365041; PMCID: PMC4986465), UC Davis (Anonymous. “What Is Equine Footing Science?” UC Davis School of Veterinary Medicine, 11 Jan. 2017, web.archive.org/web/20200812151455/ceh.vetmed.ucdavis.edu/what-equine-footing-science. Accessed 10 June 2026).
Regarding instant claim 1, 2, 4, 5, 6, 16, and 17, Pierce teaches a method of diagnosing glycoprotein biomarkers for cancer such as colorectal cancer (page 23, column 1, line 61-67, column 2, line 1-2). Pierce teaches that one of the biomarkers is the N-terminal-GLGHN amino acid sequence (page 45, Table 5, see figure 1 of this office action).
Pierce further discloses the method of diagnosing comprising obtaining a sample of a subject and analyzing the presence of the peptide in the sample. The sample can include saliva (page 23, column 2, line 7-14, “ In one embodiment, the diagnostic method involves detecting the presence of a cancer-specific glycoform of a glycoprotein in a biological sample obtained from the subject, wherein the cancer-specific glycoform comprises glycan that is indicative of the presence of cancer or a precancerous condition. The biological sample can include, without limitation a biological fluid, such as blood, serum or plasma, or it can be a tissue or organ sample” and page 35, column 25, line 17-28 “ Biological samples that can be tested in the diagnostic method of the invention include, without limitation, organs, tissues (including biopsies), fecal matter, bone marrow, lymph tissue, biological fluids, and bodily discharges obtained from a human or veterinary subject. Biological fluids may include, without being limited to, blood (including components of blood such as serum or plasma), urine, bile, spinal fluid, lymph fluid, ascites fluid, pancreatic ductal fluid, sputum, pleural fluid, tears, saliva, mucus, breast milk and bodily discharges (such as vaginal discharge, nasal discharge, and nipple aspirate)”).
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Figure 1. Pierce, page 45, Table 5, showing the sequence of N-terminal-GLGHN (SEQ ID NO: 168)
Regarding instant claims 7, 8, 9, 10, 11, and 17, Pierce discloses antibodies that binds epitopes that includes portions of the glycan moiety (page 28, column 11, line 23-25).
Regarding instant claims 13-15, Pierce teaches diagnostic methods to measure the peptide using the antibody specific for the peptide with “immunoprecipitation, immunohistochemistry, immunocytochemistry, ELISA, and immunoblotting (i.e. Western blotting). The glycoprotein biomarker can be conveniently detected using a detectably labelled antibody specific for the protein (a protein antibody). Optionally, the method may further include comparing the amount of biomarker to the amount of biomarker in a reference sample, or to a reference level, to determine whether the amount of the biomarker is indicative of the presence of cancer or a precancerous condition (page 34, column 24, line 33-44). However, Pierce does not teach lateral flow devices to measure the peptide.
Koczula teaches the lateral flow assays that use antibodies to detect peptides in saliva samples (page 1, Introduction, paragraph 1, “Lateral flow assay is a paper-based platform for the detection and quantification of analytes in complex mixtures. […] “A variety of biological samples can be tested using LFAs, including […] saliva”). Koczula further teaches that the LFAs are cheap to produce, easy to use, and rapid detection of the peptides or analytes of interest (page 1, abstract, “Lateral flow assays (LFAs) are the technology behind low-cost, simple, rapid and portable detection devices popular in biomedicine, agriculture, food and environmental sciences” and page 1, paragraph 2, “LFAs are very good candidates as they are cheap to produce, easy to use and, importantly, widely accepted by users and regulatory authorities” ). Therefore, it would have been obvious to the person of ordinary skill in the art to design a lateral flow device to detect the peptide with the antibody as taught by Pierce to allow rapid testing without requiring lab equipment.
Regarding instant claim 3 and 12, Pierce recites that biglycans are involved in the development and maintenance of bone (page 49, column 54, line 28-36, “OGN along with DCN and BGN are members of a group of small leucine-rich repeat proteoglycans (SLRPs) that are important during skeletal development. BGN and DCN are also involved in the development and maintenance of bone”). While Pierce does not teach the presence of the biglycan in bone fractures, Kram teaches that the biglycan has a role in the healing process of bone fractures, as it is elevated in the healing callus 14 days post-fracture (page 752, column 2, paragraph 2, “Biglycan has been shown to have a role in the healing process, as its expression is highly elevated in the healing callus 14 days post-fracture”). While, Pierce does not teach the disease is selected from the group consisting of bone sclerosis, chip fractures of the joint, avulsion fractures, bone bruise, and osteoarthritis as recited in claims 3 and 12. Pierce teaches that the biglycan is involved in maintenance of bone development and diagnostic methods to determine the presence of the peptide, while Kram provides evidence that biglycan is increased after bone fracture. Therefore, a person of ordinary skill in the art would have been motivated to use the biglycan peptide fragment as a diagnostic measure to determine bone fractures in a subject using Pierce and Kram’s teachings.
However, Pierce and Kram does not teach that the treatment is “resting the subject” as recited in claim 12. Martig teaches that musculoskeletal injuries are common in racehorses and that bone adaptation from increased load and training can cause chronic damage accumulation and material fatigue of the bone (abstract). Martig further discloses that resting periods are needed to allow the bone repair in the subject (page 1, abstract, “If remodelling inhibition at the extremes of training is unavoidable then the duration of exposure to high-speed work needs to be limited and appropriate rest periods instituted”). Therefore, a person of ordinary skill in the art would have been able to measure the peptide fragment N-terminal-GLGHN as taught by Pierce and that it is present in bone fractures as taught by Kram in horses that may have bone injuries and then implemented rest periods to allow bone repair as taught by Martig.
Regarding instant claim 18, Pierce, Kram and Martig do not teach the method of determining the footing for a horse arena by obtaining a sample from a horse that has been exercising on the footing and analyzing the sample for the presence of the N-terminal GLGHN peptide. UC Davis teaches that the surface variations of the footing can affect horses’ limps and impact on the bone and joint of the horse (page 1-2, surface variations, “Limp loading is also affected by the surface on which the horse performs” and “ too hard – bone, joint, hoof injuries”). UC Davis further teaches that the surface characteristics are affected by material composition, structure and maintenance (page 3, paragraph 2) and that determining the arena footing will minimize the risk for injury while optimizing horse performance (page 4, paragraph 1). Therefore, it would have been obvious to the person of ordinary skill in the art to combine determining the footing for a horse arena to optimize horse performance while reducing risk of bone injury as taught by UC Davis. A person of ordinary skill in the art would have been able to combine diagnostic assays for the N-terminal-GLGHN peptide that is part of the biglycan and is present in bone injuries in horses as taught by Pierce and Kram to optimize arena footing for horse to reduce bone injury risk as taught by UC Davis.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lam Thuy Vi Tran Ho whose telephone number is (571)272-9135. The examiner can normally be reached Monday-Friday 7:30-3.
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/LAM THUY VI TRAN HO/Examiner, Art Unit 1647 /L.T./Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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