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 .
This is the First Office Action on the Merits of US18/564,639 filed on 01/30/2024 which is a 371 of PCT/KR2022/007649 filed on 05/30/2022 which claims foreign priority KOREA, REPUBLIC OF 10-2021-0069822 filed on 05/31/2021. The Filing Receipt filed on 04/26/2024 is controlling. Please note that no English language translation of the foreign priority document is of record.
Claims 1-9 are pending and under examination.
Information Disclosure Statement
The IDS statements filed on 08/06/2025 and 11/28/2023 have 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:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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.
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.
Claims 2 and 8 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.
The term “represented by” in claims 2 and 8 is a relative term which renders the claim indefinite. The term “represented by” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, it is unclear whether represented by intends to mean “consisting of”, comprising, or having a homologous or similar amino acid sequence.
The following is a quotation of the first paragraph 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.
Written Description
Claims 1-9 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 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.
Claims 1-9 are drawn to a method of preventing or treating a vascular disease comprising: administering a composition comprising HAPLN1 as an active ingredient to a subject. Dependent claims 2 and 8 specify that the HAPLN1 is a protein fragment having an amino acid sequence represented by SEQ ID NO: 1 to the subject. Further, dependent claims 3-5 recite functional properties of the composition comprising the HAPLN1, including inhibiting and alleviating damage in elastic lamina of a vascular wall, ameliorating loss of transgelin, and suppressing phosphorylation of NF-kB or focal adhesion kinase (FAK) in vascular smooth muscle cells.
Thus, the claims require the critically essential element of a genus of HAPLN1 amino acid sequence structures having the required functional properties of being able to prevent vascular diseases in a subject and inhibiting and alleviating damage in elastic lamina of a vascular wall, ameliorating loss of transgelin, and suppressing phosphorylation of NF-kB or focal adhesion kinase (FAK) in vascular smooth muscle cells.
Consistent with the dependent claim 2 and 8, and consistent with the instant specification, the genus of HAPLN1 encompasses protein fragments having any amino acid sequence represented by SEQ ID NO: 1. However, the specification has not provided a representative set of HAPLN1 sequence structure species having the required functional properties to represent the vast number of sequence structures encompassed by the broad genus.
The instant specification shows results from only one HAPLN1 species. Such species consists of human recombinant HAPLN1 consisting of instant SEQ ID NO: 1. See FIG 1-8.
The Court of Appeals for the Federal Circuit has held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as be structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXlS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these.
When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph. In the instant case, the unpredictability of the art is evidenced in the state of the prior art of Milwid et al (WO 2011-126833 published 10/13/2011; IDS ref). Milwid et al disclose that the term HAPLN1 polypeptide refers to a polypeptide that shares certain structural and/or functional characteristics with HAPLN1. (See para 0051.) Table 2 shows a reference HAPLN1 polypeptide sequence which is reference SEQ ID NO:23. Thus, while Milwid et al provide evidence for the vast number of structural species encompassed by the present claim language, they do not provide a sufficient correlation as to whether such species also comprise the required functional properties of the present claims. (See paragraph bridging pages 21-22.)
One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). For example, adequate written description requires more than a mere statement that a compound is part of the invention and reference to a potential method of isolating a compound. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
Scope of Enablement
Claims 1-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating a vascular disease described in Figures 1-8 by administering a pharmaceutical composition comprising the HAPLN1 consisting of the sequence of SEQ ID NO: 1, does not reasonably provide enablement for preventing such disease or treating such by administering any HAPLN1 protein fragment having an amino acid sequence represented by SEQ ID NO: 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The nature of the invention and breadth of claims: The invention is drawn to preventing and treating a vascular disease by administering a fragment of the amino acid sequence of the HAPLN1 protein. The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The claims are broad to preventing any vascular disease using any fragment of the HAPLN1 protein represented by instant SEQ ID NO: 1.
The unpredictability of the art and the state of the prior art: The art teaches pharmaceutical composition comprising SEQ ID NO: 1 as the active ingredient are effective in methods of treating some vascular conditions. For example, Milwid et al teach administering "an HAPLN1 polypeptide is characterized in that, when it is administered to subjects with diseases with inflammatory diseases, one or more features of their inflammatory disease is attenuated" (see paragraph 0053 of Milwid et al US 2013/0052198). Also, Milwid et al (WO 2011-126833 published 10/13/2011; IDS ref). disclose that the term HAPLN1 polypeptide refers to a polypeptide that shares certain structural and/or functional characteristics with HAPLN1. (See para 0051.) Table 2 shows a reference HAPLN1 polypeptide sequence which is reference SEQ ID NO:23. Thus, while Milwid et al provide evidence for the vast number of structural species encompassed by the present claim language, they do not provide a sufficient correlation as to whether such species also comprise the required functional properties of the present claims. (See paragraph bridging pages 21-22.)
Guidance in the Specification and Existence of Working Example: The specification shows a method of treating certain vascular disease conditions described in Figures 1-8 by administering a pharmaceutical composition comprising the HAPLN1 consisting of the sequence of SEQ ID NO: 1. No guidance is provided for any variants of SEQ ID NO:1.
Level of Skill in the Art: The level of skill in the art is deemed to be high, at the level of an MD OR PhD research scientist.
Quantity of Experimentation is Undue: The quantity of experimentation in this area is extremely large since there is significant number of parameters which would have to be studied to enable the skilled artisan to practice the claimed invention as broadly as claimed. This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
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 nonobviousness.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Milwid et al (WO 2011-126833 published 10/13/2011).
Regarding claim 1, Milwid et al discloses a method of treating a vascular disease, comprising: administering a pharmaceutical composition comprising HAPLN1 as an active ingredient to a subject. Milwid et al disclose that the term HAPLN1 polypeptide refers to a polypeptide that shares certain structural and/or functional characteristics with HAPLN1. (See para 0051.) Table 2 shows a reference HAPLN1 polypeptide sequence which is reference SEQ ID NO:23. Milwid et al discloses treating vascular diseases including inflammatory diseases, myocardial infarction, atherosclerosis, and arteritis. (See para 0021 and Table 3). Milwid et al disclose the pharmaceutical comprises HAPLN1 as an active ingredient. (See ref claims 1, 6, 11, 16, 34, and 50-55, Table 3, and paragraphs 0094, 0095, and 00117.)
Regarding claim 2, Milwid et al discloses that the HAPLN1 is a protein fragment having an amino acid sequence represented by SEQ ID NO: 1. Table 2 shows a reference HAPLN1 polypeptide sequence which is reference SEQ ID NO:23
Regarding claim 3, Milwid et al anticipates claim 1. The claim limitation of dependent claim 3 is construed to recite the inherent property of the composition comprising HAPLN1 which inhibits and alleviates damage in elastic lamina of a vascular wall.
Regarding claim 4, Milwid et al anticipates claim 1. The claim limitation of dependent claim 4 is construed to recite the inherent property of the composition comprising HAPLN1 which inhibits ameliorates loss of transgelin.
Regarding claim 5, Milwid et al anticipates claim 1. The claim limitation of dependent claim 4 is construed to recite the inherent property of the composition comprising HAPLN1 which suppresses phosphorylation of NF-KB or focal adhesion kinase (FAK) in vascular smooth muscle cells (VSMCs).
Regarding claim 6, Milwid et al discloses that the vascular disease is one or more selected from the group consisting of arteriosclerosis, hypertension, aneurysm, hemorrhage, cerebral infarction due to vascular wall obstruction, cerebral hemorrhage, ischemic heart disease, myocardial infarction, and peripheral vascular disease.
Regarding base claim 7, Milwid et al discloses a method alleviating an inflammatory disease including a vascular disease, comprising: administering composition formulated as a food composition (such as in tablet form for oral administration) a health functional food composition administering a comprising hyaluronan and proteoglycan link protein 1 (HAPLN1) as an active ingredient to a subject. Note the instant specification discloses that a health functional food composition may be a tablet, a capsule, or a powder. (See para 60.)
Regarding claim 8, Milwid et al discloses that the HAPLN1 is a protein fragment having an amino acid sequence represented by SEQ IDNO: 1. Table 2 shows a reference HAPLN1 polypeptide sequence which is reference SEQ ID NO:23
Regarding claim 9, Milwid et al discloses that the vascular disease is one or more selected from the group consisting of arteriosclerosis, hypertension, aneurysm, hemorrhage, cerebral infarction due to vascular wall obstruction, cerebral hemorrhage, ischemic heart disease, myocardial infarction, and peripheral vascular disease. (See Table 3).
Thus, Milwid et al recite all the limitations of present claims as presently written.
The level of skill in the art was high before the effective filing date of the presently claimed invention.
In view of Milwid et al, one of ordinary skill in the art would have been motivated to administer HAPLN1 to a subject for the rationale of treating an inflammatory disease which encompasses vascular disease such as explicitly suggested as shown in Table 3.
It would have been obvious for one of ordinary skill in the art to do such because Milwid et al expressly suggests to do such.
In view of the high skill level in the art it is considered that one of ordinary skill in the art would have been motivated to follow the teachings of Milwid et al to arrive at the presently claimed invention.
Conclusion
No claim is allowed.
Related prior art which may be applied in a future office action if appropriate:
Milwid et al (US 2013/0052198). Milwid et al teach administering "an HAPLN1 polypeptide is characterized in that, when it is administered to subjects with diseases with inflammatory diseases, one or more features of their inflammatory disease is attenuated" (see paragraph 0053).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CATHERINE S HIBBERT/ Primary Examiner, Art Unit 1658
Prosecution Insights