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 .
Claim Status
Claims 1-6 and 8-9 are pending and presently considered.
Election/Restriction
The claims are reasonably understood to be directed and limited to the following subject matter:
Claims 1-6 are understood to be drawn to a method of treating or preventing ulcerative colitis comprising the single active, method step of administering (via any route) a composition comprising a protein consisting of either SEQ ID NO: 1 or SEQ ID NO: 2 (at an unspecified concentration).
Claims 8-9 are understood to be drawn to products, and reasonably inferred to be directed to polynucleotides (e.g., in the form of a gene or recombinant vector) encoding either instant SEQ ID NO: 1 or SEQ ID O: 3.
Accordingly, an election/restriction requirement has not been set forth on record at this time. However, Applicant is directed to MPEP §§ 818, 818.02(a), 819, and 821.
Priority
The priority claim to PCT/KR2022/015344 (filed 10/12/2022) is acknowledged.
Examiner notes that no certified translation of the Foreign Application KR10-2021-0151300 (filed 11/05/2021) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Information Disclosure Statement
The IDS filed 2/09/2024 is acknowledged and presently considered.
Specification
The disclosure is objected to because of the following informalities:
The instant disclosure is objected to for not complying with 37 C.F.R. 1.821 as detailed in MPEP §§ 2421–2424. Specifically, the instant application does not comply with 37 C.F.R. 1.821(b)-(e). The instant disclosure contain references or disclosures of amino acid sequences that should be accompanied by a sequence listing and identified using "SEQ ID NOs” as prescribed (see, MPEP §§ 2421–2424). Specifically, the instant application discloses sequences at least at ¶[59] of the Specification filed 2/09/2024.
Appropriate correction is required.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claims 1 and 8-9 are representative of the pending claim scope. Applicable claim interpretations are set forth below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Consisting of” excludes any elements, step, or ingredient not specified (see, e.g., MPEP § 2111.03(II)). When the phrase "consists of" appears in a clause of the body of a claim, rather than immediately following the preamble, the "consisting of" phrase limits only the element set forth in that clause; other elements are not excluded from the claim as a whole (see, e.g., MPEP § 2111.03(II)).
For purposes of examination, claim 1 is understood to be drawn to a method of treating or preventing ulcerative colitis comprising the single, active method step of administering (via any route) a composition comprising a protein consisting of either SEQ ID NO: 1 or SEQ ID NO: 2 (at an unspecified concentration). The usage of “consisting of” is understood to limit the claim scope to the exact, two sequences of SEQ ID NO: 1 and SEQ ID NO: 2, wherein N- or C-terminal extensions are excluded.
Claim 1 recites that the protein is “recombinant”, which is understood to be a product-by-process limitation nested within a method claim. The proper analysis of product-by-process language nested within a method of treatment has been directly addressed by the Federal Circuit in Biogen MA Inc. v. EMD Serono, Inc. (976 F.3d 1326, 2020 U.S.P.Q.2d 11129 (Fed. Cir. 2020); hereafter “Biogen”). The Court in Biogen specifically identified that
...a source limitation alone cannot confer novelty unless the product itself is novel.
(see, e.g., Biogen at 1332);
The nesting of the product-by-process limitation within a method of treatment claim does not change the proper construction of the product-by-process limitation itself.
(see, e.g., Biogen at 1334); and
There is no logical reason why the nesting of a product-by-process limitation within a method of treatment claim should change how novelty of that limitation is evaluated.
(see, e.g., Biogen at 1334).
The Court explained that not applying product-by-process analysis to method claims
....could have the absurd result that a recombinant composition could be non-novel, the method of administration could be non-novel, but the method of administration of the composition defined by the process of its manufacture would be novel as a matter of law.
(see, e.g., Biogen at 1334).
Accordingly, the product-by-process language at claim 1 is properly interpreted under MPEP § 2113. Critically, “even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself” (see, e.g., MPEP § 2113). Accordingly, the nested product-by-process limitations pertaining to the source of a material used within the method of the independent claim are presently understood to be fully satisfied by any prior art pharmaceutical product satisfying the structure implied by the product-by-process language at instant claim 1. Here, at most, the structure implied by the product-by-process language of instant claim 1 includes any peptide “consisting of SEQ ID NO: 1 or SEQ ID NO: 3”. Therefore, any prior art teaching the process and pharmaceutical product of claim 1, having the exact structure claimed is understood to fully satisfy the product-by-process limitations set forth at instant claim 1.
Within the “wherein” clauses at dependent claims 2-5, the recitation “compared with a case in which the recombinant protein is not administered” is not reasonably interpreted as an active method step requiring performance of a control case in a subject, but instead the “wherein” clause is understood in context to recite the intended and expected outcomes that follow the performance of the active method steps at claim 1. This is reasonable because the alternative interpretation of the phrase “a case in which the recombinant protein is not administered” would require potentially unethical lack of treatment of a subject (e.g., a human) or otherwise identification and clarification of the metes and bounds of a control case, which does not exclude a control case using natural MFG-E8 that comprises but does not consist of SEQ ID NO: 1 or 3. Notably, the Specification does not identify that MFG-E8 treatment was statistically different than treatment with NP-011 (see, e.g., Spec. filed 2/09/2024 at Table 3 at ¶[88], noting that all determinations of statistical significance were made relative to the “UC” sample rather than the closest existing prior art sample). Accordingly, the “wherein” statements at claims 2-5 are understood to be recitations of intended and expected results explaining what performance of the active method step at claim 1 is intended and expected to achieve.
Regarding the “wherein” clauses at dependent claims 2-5 stating:
…wherein the recombinant protein reduces, compared with a case in which the recombinant protein is not administered, degrees of crypt damage, an inflammation severity, and an inflammation extent in a mucosa of a large intestinal tissue that is a target for treatment or prevention;
…wherein the recombinant protein reduces, compared with a case in which the recombinant protein is not administered, degrees of erosion and epithelial hyperplasia in a mucosa of a large intestinal tissue that is a target for treatment or prevention;
…wherein the recombinant protein reduces, compared with a case in which the recombinant protein is not administered, a concentration of interleukin-6 (IL-6) in blood of a target for treatment or prevention; and
…wherein the recombinant protein reduces, compared with a case in which the recombinant protein is not administered, degrees of weight loss and colon length shrinkage caused by ulcerative colitis of a target for treatment or prevention;
These “wherein” clauses do not appear to correspond to any “hand-of-man” active method steps, or defined functional limitations of record corresponding to specific structures or steps. Rather, these “wherein” clauses appear to only recite intended and expected results fully satisfied by the positively recited active method steps set forth at instant claim 1 (i.e., the step of “administering a composition comprising” a peptide consisting of SEQ ID NO: 1 or SEQ ID NO: 3 to a subject). Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Accordingly, the “wherein” clauses at claims 2-5 are understood to merely recite intended or expected results fully satisfied by the positively recited steps and/or structures set forth in the body of the claim 1. Therefore, the “wherein” clauses of claims 2-5 are understood to be necessarily fully satisfied by any prior art embodiments that satisfy the steps of instant claim 1. If Applicant disagrees, Applicant should clearly and unambiguously identify how the “wherein” clauses further limit the active method steps performed relative to claim 1 with respect to the “hand-of-man” steps performed, patient population, composition administered, dosage, dosage frequency, dosing regimen, formulation, etc., etc.
At claim 1, the phrase “as an active ingredient” is a recitation of an intended result, but is non-limiting per MPEP § 2112.01(II) and In re Spada, which explains that "Products of identical chemical composition can not have mutually exclusive properties” and “A chemical composition and its properties are inseparable”, therefore, “if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” Therefore, if present, the compound will necessarily act “as an active ingredient”.
At claim 6, the phrase “is formulated for” requires active formulation of a composition comprising peptides consisting of SEQ ID NO: 1 or 3 suitable for the intended administration route, but does not require administration by the recited route. This distinction is important because if the composition is suitable for use in “intralesional administration”, then it is necessarily “formulated for intralesional administration” as required by claim 6; however, if such formulation is also suitable for oral administration and administered orally, then the limitations of both claim 1 and 6 are satisfied because claim 6 does not actually recite and require intralesional administration to be performed.
For purposes of examination, claims 8-9 are understood to be drawn to products, and reasonably inferred to be directed to polynucleotides (e.g., in the form of a gene or recombinant vector) encoding either instant SEQ ID NO: 1 or SEQ ID O: 3.
Additional claim interpretations are discussed below.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 currently recites “administering a composition comprising recombinant protein based on milk fat globule-EGF Factor 8 (MFG-E8) protein, consisting of an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3, as an active ingredient, to a subject”.
First, this phrase is grammatically incorrect and should contain the article “a” between “comprising” and “recombinant” to yield “a composition comprising a recombinant protein…”.
Second, the usage of the phrase “based on milk fat globule-EGF Factor 8 (MFG-E8) protein” is superfluous. The phrase is non-limiting and non-clarifying in view of subsequent limitation requiring that the protein “consist[s] of …. SEQ ID NO: 1 or SEQ ID NO: 3”. Superfluous language should be removed to minimize confusion and to clarify claim scope.
Third, the phrase “as an active ingredient” is superfluous and non-limiting because, per MPEP § 2112.01(II) and In re Spada, "[p]roducts of identical chemical composition can not have mutually exclusive properties” and “A chemical composition and its properties are inseparable”, therefore, “if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” Accordingly, if present, a protein consisting of SEQ ID NO: 1 or SEQ ID NO: 3 will necessarily and inherently act “as an active ingredient”. Superfluous language should be removed to minimize confusion and to clarify claim scope.
Appropriate correction is required.
Claim Rejections
Claim Rejections - 35 USC § 112(b)
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 2-3 and 5 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 2 refers to “degrees of crypt damage, an inflammation severity, and an inflammation extent in a mucosa of a large intestinal tissue”, which renders the claim scope indefinite. The phrase at claim 2 is understood to recite relative terms regarding a subjective and undisclosed histological scoring metric (“degrees”) that is not defined on record, which renders the claim indefinite. The phrase 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, but would instead be aware that histological scoring for “assessing grade severity…are complex and/or subjective” even post-filing (see, e.g., Villanacci1 at title, abs, passim). Accordingly, the metes and bounds of what does or does not constitute “degrees” is unclear and therefore the boundaries of infringement are unknown. For purposes of applying prior art, the “wherein” statement at claim 2 is understood to a recitation of intended and expected results fully satisfied by the performance of the positively recited active method step set forth within the body of independent claim 12.
Claim 3 refers to “degrees of erosion and epithelial hyperplasia in a mucosa of a large intestinal tissue”, which renders the claim scope indefinite. The phrase at claim 3 is understood to recite relative terms regarding a subjective and undisclosed histological scoring metric (“degrees”) that is not defined on record, which renders the claim indefinite. The phrase 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, but would instead be aware that histological scoring for “assessing grade severity…are complex and/or subjective” even post-filing (see, e.g., Villanacci at title, abs, passim). Accordingly, the metes and bounds of what does or does not constitute “degrees” is unclear and therefore the boundaries of infringement are unknown. For purposes of applying prior art, the “wherein” statement at claim 3 is understood to a recitation of intended and expected results fully satisfied by the performance of the positively recited active method step set forth within the body of independent claim 13.
Claim 5 refers to “degrees of weight loss and colon length shrinkage caused by ulcerative colitis”, which renders the claim scope indefinite. The phrase at claim 3 is understood to recite relative terms regarding a subjective and undisclosed histological scoring metric (“degrees. . . caused by ulcerative colitis”) that is not defined on record, which renders the claim indefinite. The phrase 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, but would instead be aware that histological scoring for “assessing grade severity…are complex and/or subjective” even post-filing (see, e.g., Villanacci at title, abs, passim). Accordingly, the metes and bounds of what does or does not constitute “degrees” is unclear and therefore the boundaries of infringement are unknown as “degrees” of weight loss may include BMI reduction or loss of pounds, and identification of causation is not defined on record (i.e., claim 5 requires “degrees…. caused by ulcerative colitis”, and therefore excludes “degrees” caused by life-style choices, comorbidities, etc.) For purposes of applying prior art, the “wherein” statement at claim 5 is understood to a recitation of intended and expected results fully satisfied by the performance of the positively recited active method step set forth within the body of independent claim 14.
Accordingly, claims 2-3 and 5 are rejected as indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2-5 and 8-9 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 2-5 depend from instant claim 1, and only differ from claim 1 by the recitation of a “wherein” clause that appears to only recite intended and expected results of a positively recited active method step within the body of claim 1 (i.e., administration of a composition comprising a peptide consisting of SEQ ID NOs: 1 or 2 to a subject). Accordingly, such “wherein” are not functional limitations corresponding to specific structural limitations of record, but instead the clauses merely recite hoped-for and desired results without describing any additional steps or altered parameters required to achieve such steps. Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Accordingly, claims 2-5 are rejected as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends.
Claims 8-9 are product claims that depend from method claims. Per MPEP § 608.01(n)(III),
The fact that the independent and dependent claims are in different statutory classes does not, in itself, render the latter improper . . . . On the other hand, if claim 1 recites a method …. a claim to the product set forth in claim 1 would not be a proper dependent claim if the product can be made by a method other than that recited in the base method claim, and thus, does not include the limitations of the base claim.
Here, claims 8-9 (product claims) depend from claim 1 (a method claim), and claim 1 requires that the products “consist[] of an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3”. However, claims 8-9 are not limited to those sequences, but instead are directed to polynucleotides “encoding the recombinant protein”. This is broader than claim 1 because a polynucleotide “encoding the recombinant protein” of claim 1 includes entire human genes encoding full-length MFG-E8 proteins (compare instant SEQ ID NO: 1 with US 7,718,851 B2 at title, abs, claims 1 and 9, col 12 at lines 34-40, and SEQ ID NO: 8, wherein US’851 at SEQ ID NO: 8 is a polynucleotide and gene encoding instant SEQ ID NO: 1, and wherein US’851 identifies and claims methods of utilizing the sequence in a gene and expression vector; compare instant SEQ ID NO: 3 with US2018/0334486A1 at sequence at Fig. 2 and claims 1 and 3-4, wherein US’486 claims and discloses genes and recombinant vectors comprising SEQ ID NO: 1). Accordingly, the scope of claims 8-9 more broadly encompass genes and vectors that “encode” SEQ ID NO: 1 or SEQ ID NO: 3, but are not limited to sequences “consisting of” SEQ ID NO: 1 and SEQ ID NO: 3. Therefore, claims 8-9 are rejected as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 8-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the naturally-occurring gene of human MFG-E8 without significantly more.
Claim 8 recites “a gene encoding the recombinant protein according to claim 1” (i.e., gene encoding instant SEQ ID NO: 1 or SEQ ID NO: 3), and claim 9 differs from this by further reciting a “recombinant vector comprising a gene encoding the recombinant protein according to claim 1”.
Instant SEQ ID NO: 1 and 3 correspond to naturally occurring peptides encoded by the human genome. Specifically, instant SEQ ID NO: 1 corresponds to a naturally occurring human gene, as evidenced by GenBank: EAX02025.15 (compare instant SEQ ID NO: 1 with EAX02025.1, showing 100% identity); and instant SEQ ID NO: 3 corresponds to a naturally occurring human gene, as evidenced by NCBI Reference Sequence: XP_016877695.16 (compare instant SEQ ID NO: 3 with XP_016877695.1, showing 100% identity).
The term “recombinant” is product-by-process language and does not structurally differentiate the claimed products relative to the naturally occurring substances.
Regarding claim 8, the naturally occurring gene naturally encodes instant SEQ ID NOs: 1 and 3, and therefore claim 8 is directed to a naturally occurring product without significantly more.
Regarding claim 9, the relevant issue is whether or not the requirement for a “recombinant vector” is “significantly more” than the naturally occurring gene. “To be patent eligible, a claim that is directed to a judicial exception must include additional features to ensure that the claim describes a process or product that applies the exception in a meaningful way, such that it is more than a drafting effort designed to monopolize the exception” (79 FR 74624 col I). Here, the phrase “recombinant vector” does not recite or require any specific structure, but instead refers to a general and routine concept in the art, namely that genes may be inserted into vectors for routine assays, study, and development. Therefore, in the absence of any particular structural limitation, the mere recitation of “recombinant vector” does not meaningfully differentiate the claim scope relative to the naturally occurring gene because such language “consists of well understood, routine, conventional activity already engaged in by the scientific community” (see, e.g., 79 FR 74627 at Example 5 at col III at 1st full ¶; see also Mayo, 101 USPQ2d 1961 at 1968; see also Mayo, 132 S. Ct. at 1294, explaining that eligibility does not “depend simply on the draftsman’s art”; see also Myriad, 133 S. Ct. at 2116-19, clarifying that not every change to a product will result in a marked difference, and that the mere recitation of particular words (e.g., “isolated”) in the claims does not automatically confer eligibility).
Summary
“To be patent eligible, a claim that is directed to a judicial exception must include additional features to ensure that the claim describes a process or product that applies the exception in a meaningful way, such that it is more than a drafting effort designed to monopolize the exception” (79 FR 74624 col I), and the Courts have made clear that to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature coupled with an instructions equivalent to saying "apply it" (see Mayo, 101 USPQ2d 1961 at 1965).
In sum, when the relevant considerations are analyzed, they weigh against a significant difference. Accordingly, claims 8-9 do not qualify as eligible subject matter.
Claim Rejections - 35 USC § 112(a), Scope of Enablement
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 1-6 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 the treatment of ulcerative colitis, does not reasonably provide enablement for preventing ulcerative colitis as recited by the preamble of claim 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.
The applicable legal standards for enablement are discussed at MPEP § 2164 and the specific legal standards relevant to determinations regarding the scope of enablement are set forth at MPEP § 2164.08. MPEP § 2164 identifies the following relevant factors for determining “undue” experimentation: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.” The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims and nature of the invention: Claims 1-6 are directed to methods of “preventing” ulcerative colitis” in any subject by administering (via any route of administration) a composition comprising a peptide consisting of either SEQ ID NO: 1 or SEQ ID NO: 3, at an unspecified concentration. Therefore, the claim scope includes “preventing” ulcerative colitis.
The amount of direction or guidance presented and the existence of working examples: The originally filed disclosure discloses zero guidance regarding the prevention of ulcerative colitis. Zero evidence of record suggests or otherwise establishes that ulcerative colitis can be “prevented” using the claimed methods.
The state of prior art: The lack of guidance and working examples is pertinent because the prior art and post-filed art establishes that no means of preventing ulcerative colitis is known in the art. For example, Curtis7 identifies that “There is no known way to prevent ulcerative colitis” (see, e.g., Curtis at 2) circa 2026. Notably, the lack of prevention post-filing evidences that no enabled means of preventing ulcerative colitis existed in the prior art.
Relative skill of those in the art, and the predictability or unpredictability of the art: Although the relative skill in the art is high, the general predictability of the art regarding the complete prevention of ulcerative colitis is very low because whole organism medical treatments are subject to high variability based upon subject parameters (e.g., age, weight, gender, and state of health), route of administration, dosage, therapeutic windows, etc. Furthermore, as evidenced by Curtis, discussed above, an artisan would readily appreciate that prevention of Ulcerative Colitis prior to 2026 was not possible because the art of 2026 literally identifies that “There is no known way to prevent ulcerative colitis” (see, e.g., Curtis at 2).
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of treating ulcerative colitis were known in the art at the time of the invention, it was not routine or recognized as possible in the art to prevent ulcerative colitis as claimed. Accordingly, in the complete absence of any supporting evidence or biochemical mechanisms supporting “prevention”, one of skill in the art would not reasonable conclude that prevention of ulcerative colitis was possible prior to 2026. Therefore, at the time of filing, an artisan would have reasonably doubted that such activity was possible to achieve in the absence of credible and substantial guidance. No such credible and substantial guidance has been set forth on record. Accordingly, a substantial and undue amount of experimentation would be required to practice the prevention of ulcerative colitis as instantly claimed, based upon the limited teachings and evidence of record, and such prevention may not be possible.
Conclusion: Therefore, in view of the lack of guidance and working examples, high degree of unpredictability, and failure to address the concerns present in the art, an artisan would be unduly burdened with experimentation in order to practice the full scope of the instantly claimed invention.
Accordingly, claims 1-6 are rejected. Applicant is advised that this rejection could be resolved by amending/redrafting claim 1 to remove “or preventing”.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 8-9 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 7,718,851 B2.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. This rejection pertains to SEQ ID NO: 1.
Regarding instant claims 8-9, for purposes of the instant rejection, claims 8-9 are understood to be directed to a gene encoding SEQ ID NO: 1 or a vector encoding SEQ ID NO: 1, respectively. The primary reference teaches and discloses the expression of human milk proteins in transgenic plants (see, e.g., US’851 at title, abs, claims 1 and 9). This is pertinent because US’851 discloses and claims sequences encoding instant SEQ ID NO: 1, namely US’851 discloses SEQ ID NO: 8 (compare US’851 at SEQ ID NO: 8 and col. 27 at lines 54-58 with instant SEQ ID NO: 1, noting that upon translation, SEQ ID NO: 8 of US’831 shares 100% sequence identity with instant SEQ ID NO: 1). Critically, US’831 teaches and claims methods utilizing vectors (chimeric genes) suitable for transforming plant cells that include SEQ ID NO: 8 (see, e.g., US’831 at claims 1 and 9, col 12 at lines 34-55 and col. 13 at lines 10-26). Accordingly, an artisan would at once envisage recombinant vectors sufficient to transform plant cells in order to practice the claimed invention.
Accordingly, claims 8-9 are anticipated by the prior art.
Claims 8-9 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US2018/0334486A1.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. This rejection pertains to SEQ ID NO: 3.
Regarding instant claims 8-9, for purposes of the instant rejection, claims 8-9 are understood to be directed to a gene encoding SEQ ID NO: 3 or a vector encoding SEQ ID NO: 3, respectively. US’486 teaches, discloses and explicitly claims “a gene encoding the recombinant protein of claim 1” (see, e.g., US’486 at claim 3) and a “recombinant vector comprising the recombinant protein-encoding gene of claim 3” (see, e.g., US’486 at claim 3), wherein claim 1 recites the protein of SEQ ID NO: 1, which fully comprises and shares 100% sequence identity with instant SEQ ID NO: 3 (compare US’486 at claim 1, SEQ ID NO: 1, Figs. 1-2 with instant SEQ ID NO: 3). Accordingly, genes and vectors comprising genes encoding instant SEQ ID NO: 3 were already known and claimed in the prior art.
Accordingly, claims 8-9 are anticipated by the prior art.
Claims 8-9 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by KR20200046869A8 as evidenced by Machine Translation9.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. This rejection pertains to SEQ ID NO: 1.
Regarding instant claims 8-9, for purposes of the instant rejection, claims 8-9 are understood to be directed to a gene encoding SEQ ID NO: 1 or a vector encoding SEQ ID NO: 1, respectively. KR’869 directly recites and claims “a gene encoding a recombinant protein” of claim 1 and a “recombinant vector comprising a gene encoding a recombinant protein” of claim 1, wherein claim 1 refers to a recombinant protein having the sequence of SEQ ID NO: 1 (see, e.g., KR’869 at claims 1, 6, 7, and SEQ ID NO: 1; see Translation at claims 1, 6, 7, and SEQ ID NO: 1).
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SEQ ID NO: 1 and instant SEQ ID NO: 1 are 100% identical 202-mer sequences. Accordingly, instant claims 8-9 have the same scope and structure as the prior art structure of KR’869.
Accordingly, claims 8-9 are anticipated.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang10 in view of KR20200046869A11 as evidenced by Machine Translation12.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. This rejection pertains to SEQ ID NO: 1.
Regarding claims 1-6 and methods of treating ulcerative colitis, Zhang teaches and discloses that the usage of recombinant human MFG-E8 (rhMFG-E8) to reduce inflammation and treat ulcerative colitis via daily subcutaneous injections of rhMFG-E8 at 60 or 120 µg/lg/day was already known in the prior art, and had been shown to attenuate colitis in a dose-dependent manner (see, e.g., Zhang at title, abs, 480 at col I at 1st ¶, Table 1 at 481, 482-483 at § Results, Fig. 1 on 483, 486 at col I-II, 489 at col I at final ¶ to col II at 3rd ¶). In addition, Zhang teaches and discloses that such treatment predictably ameliorates ulcerative colitis by decreasing weight loss, decreasing colitis severity scores, and colon shrinkage compared with vehicle controls (see, e.g., Zhang at title, 489 at col I at final ¶ to col II at 3rd ¶). In sum, Zhang teaches and discloses methods of administering rhMFG-E8 (i.e., a 364-mer peptide) to subjects to successfully treat colitis.
Zhang differs from instant claims 1-6 as follows: Zhang does not disclose a method of performing the same exact treatment for ulcerative colitis, but wherein a truncated 202-mer peptide (i.e., instant SEQ ID NO: 1) is substituted in place of full-length rhMFG-E8. Therefore, the relevant issue is whether or not it would have been obvious to utilize a truncated form of MGF-E8 in the prior art methods of treating ulcerative colitis.
The truncated form of instant SEQ ID NO: 1 was already known in the prior art: KR’869 discloses an MFG-E8 based protein (see, e.g., KR’869 at abs), and specifically claims and discloses SEQ ID NO: 1 (see, e.g., KR’869 at claims 1, 6, 7, and SEQ ID NO: 1; see Translation at claims 1, 6, 7, and SEQ ID NO: 1).
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SEQ ID NO: 1 and instant SEQ ID NO: 1 are 100% identical 202-mer sequences. Accordingly, the truncated sequence is not a point of novelty.
The prior art teaches that truncated SEQ ID NO: 1 was based upon MGF-E8 and discloses that the sequence was active and capable of treating an inflammation-based disease successfully (see, e.g., KR’869 at abs, Background, claims; see, e.g., Translation at claims 1-7, page 3 at 1st ¶ discussing inflammation). KR’869 identifies that the truncated form of MFG-E8 was functional, and could be formulated for multiple administration routes, and additional claims genes and recombinant vectors encoding the truncated peptide (compare Translation at claims 4-7 with instant claims 6 and 8-9).
Accordingly, the basic question is whether or not an artisan would simply substitute the truncated from of MFG-E8 taught by KR’869 in place of full-length rhMFG-E8 in the method of treating ulcerative colitis as taught by Zhang, with a reasonable expectation of successfully achieving the results taught and disclosed by Zhang. Here, because KR’869 teaches that the truncated peptide was functional and could be successfully utilized to treat other inflammation-related diseases, an artisan would reasonably expect that the truncated peptide would work successfully as an equivalent to full-length rhMFG-E8. Furthermore, shorter peptides would be cheaper to manufacture.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the simple substitution of one known, functional MFG-E8 based protein (e.g., SEQ ID NO: 1 of KR’869) for another known, functional MFG-E8 based protein (e.g., rhMFG-E8) in the method of treating ulcerative colitis as taught and disclosed by Zhang, wherein such substitution would be reasonably predicted to yield successful treatment of inflammation and ulcerative colitis (see, e.g., MPEP §§ 2143(I)(B), (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well within the ordinary skill in the art to substitute one functional MFG-E8 based protein for another into known methods.
Accordingly, claims 1-6 and 8-9 are rejected.
Claims 1-6 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang13 in view of KR20200046869A14 as evidenced by Machine Translation15 as applied to claims 1-6 and 8-9, above, and in further view of GenBank: EAX02025.116 and NCBI Reference Sequence: XP_016877695.117.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. This rejection pertains to SEQ ID NO: 3.
The teachings of Zhang in view of KR’869 as evidenced by Translation as applied to claims 1-6 and 8-9 have been discussed above, and those discussions are incorporated into the instant rejection.
The teachings of Zhang in view of KR’869 as evidenced by Translation differ from claims 1-6 and 8-9 as practiced with instant SEQ ID NO: 3 as follows: Zhang and KR’869 do not teach practicing the method of treating ulcerative colitis using a truncated MFG-E8 based protein of SEQ ID NO: 1 having an M53L mutation (i.e., to arrive at instant SEQ ID NO: 3).
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(alignment shows instant SEQ ID NO: 1 and 3, aligned).
Human MFG-E8 proteins were known to naturally exhibit a M53L mutation: Instant SEQ ID NO: 1 and 3 correspond to naturally occurring peptides encoded by the human genome. Specifically, instant SEQ ID NO: 1 corresponds to a naturally occurring human gene, as evidenced by GenBank: EAX02025.1 (compare instant SEQ ID NO: 1 with EAX02025.1, showing 100% identity); and instant SEQ ID NO: 3 corresponds to a naturally occurring human gene, as evidenced by NCBI Reference Sequence: XP_016877695.1 (compare instant SEQ ID NO: 3 with XP_016877695.1, showing 100% identity). These naturally occurring MFG-E8 proteins differ at position M53L, and M53L is not disclosed as associated with diseases states or abrogated functionality. Accordingly, the M53L mutation was known in the prior art, but would not be expected or predicted to alter functionality of an MFG-E8 protein.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the simple substitution of one known, functional MFG-E8 based protein (e.g., SEQ ID NO: 1 of KR’869) for another known, functional MFG-E8 based protein (e.g., rhMFG-E8) in the method of treating ulcerative colitis as taught and disclosed by Zhang, wherein such substitution would be reasonably predicted to yield successful treatment of inflammation and ulcerative colitis, and wherein in view of EAX02025.1 and XP_016877695.1, an artisan would readily appreciate that such MFG-E8 based proteins could optionally include M53L mutations without abrogating or substantially altering the activity of the MFG-E8 based proteins (see, e.g., MPEP §§ 2143(I)(B), (G); see also KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 417, noting that “If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability”).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well within the ordinary skill in the art to substitute one functional MFG-E8 based protein for another into known methods.
Accordingly, claims 1-6 and 8-9 are rejected.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Examiner notes that the prior art provides substantial guidance regarding expected and predicted applications of MFG-E8 based proteins (e.g., compare instant SEQ ID NO: 1 with sequence 85 from patent US 9238080; or with sequence 1 from patent US 9669070; or with sequence 85 from patent US 9718892; or with sequence 85 from patent US 10407512; or with sequence 6 from patent US 5972337; or with sequence 78 from patent US 7084249; or with sequence 2 from patent US 7781414; or with sequence 7 from patent US 7704964; or with sequence 16 from patent US 9453050, all showing 100% sequence identity with instant SEQ ID NO: 1). This is not exhaustive.
KR1020180128033B1 (May 7, 2020) as evidenced by Translation of KR’03318 is understood to pertain to methods of administering instant SEQ ID NO: 1 to subjects for “preventing or treating myocardial infarction” (see, e.g., KR’033 at front page, abs, title, claims; see Translation of KR’033 at title, abs, claims).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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, Lianko G. Garyu can be reached at (571) 270-7367. 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.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 Villanacci et al., Inflammatory Bowel Diseases: Does One Histological Score Fit All? Diagnostics (Basel). 2023 Jun 19;13(12):2112. doi: 10.3390/diagnostics13122112. PMID: 37371007; PMCID: PMC10296999; hereafter “Villanacci”.
2 Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”.
3 Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”.
4 Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”.
5 GenBank: EAX02025.1, milk fat globule-EGF factor 8 protein, isoform CRA_a [Homo sapiens], NCBI GenPept Database, PRI 23-March-2015, 2 pages; also available at https://www.ncbi.nlm.nih.gov/protein/EAX02025.1 (last visited 5/22/2026)
6 NCBI Gen Pept Reference Sequence: XP_016877695.1, lactadherin isoform X2 [Homo sapiens], NCBI GenPept Database, PRI 17-AUG-2020, 2 pages; also available at https://www.ncbi.nlm.nih.gov/protein/1034590670?sat=48&satkey=130977113 (last visited 5/22/2026); hereafter “XP_016877695.1”.
7 Curtis, How to Prevent Ulcerative Colitis, Health.com, 13 pages (Jan. 7, 2026), also available at https://www.health.com/ulcerative-colitis-prevention-8633457 (last visited 5/22/2026); hereafter “Curtis”.
8 Cited in IDS filed 2/09/2024 as Cite No. 1.
9 Machine Translation of KR20200046869A, Translated by MOIP of Korea on 5/22/2026, 16 pages
10 Zhang et al., Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice. Lab Invest. 2015 May;95(5):480-90. doi: 10.1038/labinvest.2015.32. Epub 2015 Mar 9. PMID: 25751740.
11 Cited in IDS filed 2/09/2024 as Cite No. 1.
12 Machine Translation of KR20200046869A, Translated by MOIP of Korea on 5/22/2026, 16 pages
13 Zhang et al., Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice. Lab Invest. 2015 May;95(5):480-90. doi: 10.1038/labinvest.2015.32. Epub 2015 Mar 9. PMID: 25751740; cited in previous action.
14 Cited in IDS filed 2/09/2024 as Cite No. 1.
15 Machine Translation of KR20200046869A, Translated by MOIP of Korea on 5/22/2026, 16 pages
16 GenBank: EAX02025.1, milk fat globule-EGF factor 8 protein, isoform CRA_a [Homo sapiens], NCBI GenPept Database, PRI 23-March-2015, 2 pages; also available at https://www.ncbi.nlm.nih.gov/protein/EAX02025.1 (last visited 5/22/2026)
17 NCBI Gen Pept Reference Sequence: XP_016877695.1, lactadherin isoform X2 [Homo sapiens], NCBI GenPept Database, PRI 17-AUG-2020, 2 pages; also available at https://www.ncbi.nlm.nih.gov/protein/1034590670?sat=48&satkey=130977113 (last visited 5/22/2026); hereafter “XP_016877695.1”.
18 Translation of KR1020180128033B1, Translated by MOIP of Korea on 5/22/2026, 12 pages
Prosecution Insights