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 .
Instant Action Supersedes Action Mailed 7/29/2026
Per MPEP § 710.06, this action corrects an error in the Action mailed 7/29/2026, wherein the prior action inadvertently identified the Period for Reply as “2 months” rather than “3 months”. No other changes have been made.
Copies of references and the signed IDS were already placed on record, and are not attached to the instant action.
Claim Status
Claims 1-25 are pending as filed 12/22/2023. Claims 1-23 are withdrawn as directed to a non-elected invention (i.e., non-elected Groups I, II, and III). Claims 24-25 are presently considered.
Election/Restriction Requirement
Applicant’s election of Group IV (original claims 24-25 as filed 12/22/2023) and the species of Examples wherein the peptide CL04183 (SEQ ID NO: 55) is administered to mammals via parenteral injection at 2.5 mg/kg at days 0, 2, and 4 as disclosed at pages 37-39 and 42 of the specification, in the reply filed on 7/08/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The species requirement required election of a single, disclosed species by identification of a single example (see Requirement mailed 2/09/2026 at 8-9). Upon review of the description, the originally elected species is understood to correspond to the in vivo treatment of mice as described at page 42, wherein male mice were implanted with human CRC29 colorectal cancer organoids containing firefly luciferase, which formed a primary tumor, received carpofen 30 minutes before surgery and the day after, and then 14 days after transplantation, the mice were sedated using isoflurance, injected with 50 mg/kg ‘5-Fluorouracil (5-FU) by i.p. injection, and then seven days later, administered CL04183 (e.g., SEQ ID NO: 551) via parenteral (i.v.) injection at 2.5 mg/kg at day 0, and then administration of CL04183 was repeated 2 and 4 days later (see, e.g., Spec. filed 12/22/2023 at 42 at lines 14-27).
The originally elected species is therefore understood to read upon instant claims 24-25 as follows: At claim 24, the “subject in need thereof” is a mammal (i.e., mice) with a CRC29 colorectal cancer organoid formed primary tumor, the “disease or condition caused by…cancer cells” is treated by administering the “pharmaceutical composition according to claim 22” of instant SEQ ID NO: 552 to the subject at an “effective amount” of “2.5 mg/kg” at days 0, 2, and 4, via the administration route of i.v. injection. At claim 25, the anti-cancer chemotherapeutic agent is understood to be ‘5-Fluorouracil (5-FU).
Following extensive search and examination, the originally elected species has been deemed free of the prior art. Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Examiner notes that examination need not be extended beyond a proper Markush Grouping per MPEP § 803.02(III). Per MPEP § 803.02(III), examination was extended to a non-elected species of administering instant SEQ ID NO: 21 at 5 or 10 mg/kg to mice in need of treatment or prevention of senescence and/or age-related conditions, following administration of doxorubicin.
Following extensive search and examination, the non-elected species was deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III), claims directed to other nonelected species have been withdrawn.
Claims 1-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/08/2026.
Accordingly, claims 24-25 are presently considered.
Denial of Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, US Provisional 62/979819 (filed 2/21/2020) fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163.
Lack of Express Support
Claims 22, 24, and 25 are representative of the pending claim scope. Neither claim literally appears in Pro’819, and therefore the claims lack literal support in the Pro’819. More specifically, instant claims 22 and 24-25 encompass instant SEQ ID NO: 553, but instant SEQ ID NO: 55 is literally absent from the claims and disclosure of Pro’683. Notably, Pro’819 fails to disclose the sequence, examples, or figures pertinent to the originally elected species (e.g., no methods of administering CL04183 to any subject, in vivo or otherwise, was literally disclosed in the provisional).
Accordingly, this evidences that the scope of Pro’819 at claims 27 and 28 are materially distinct from the scope of instant claims 24-25.
Accordingly, Pro’819 fails to provide literal support for the pending claim scope that is synonymous or equivalent in scope.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163. In the absence of express support, the relevant issue is whether or not the claimed invention is supported by Pro’819 through implicit or inherent disclosures.
Upon review, zero inherent or implicit support commensurate in scope with the metes and bounds of the instant claims is found in Pro’819, at least because zero guidance exists that would direct an artisan to the pending claim scope, which includes species such as instant SEQ ID NO: 55, “effective dosages” thereof, and patient populations (see elected species), that were not literally, implicitly, or inherently disclosed by the provisional. According the claim language presently claimed is not supported by the provisional document by synonymous or equivalent language.
Accordingly, Pro’819 fails to provide implicit or inherent support for the pending claim scope that synonymous or equivalent in scope, or otherwise commensurate in scope with the pending claims.
Conclusion
Accordingly, priority to US Provisional 62/979819 (filed 2/21/2020) is denied for claims 24-25 and all of the dependents of those claims; these claims have been accorded a priority date of 2/22/2021, which corresponds to the filing date of PCT/EP2021/054338.
Information Disclosure Statement
The IDS filed 12/29/2023 and 10/28/2025 are each acknowledged and presently considered.
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).
Claim 24 is representative of the pending claim scope and presently recites:
24. A method for treating or preventing a disease or condition caused by senescent cells, scarred cells, and/or cancer cells; age-related diseases; kidney disease; non-alcoholic steohepatitis (NASH) / non-alcoholic fatty liver diseases (NAFLD); liver fibrosis; idopathic pulmonary fibrosis (IPF); amyotrofic lateral sclerosis (ALS); osteoarthritis; COPD; musculoskeletal diseases; reductions of cognitive functions; or cancer, in a subject in need thereof, comprising administering to said subject, an effective amount of the pharmaceutical composition according to claim 22.
Accordingly, the claimed invention is directed to methods of treating and preventing numerous “disease or conditions caused by” a variety of sources, ranging from different cells, COPD, cancer, “reductions of cognitive function”, etc. 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)).
“Subject” is not specifically defined, but is understood to include at least mammals, including humans (see, e.g., Spec. filed 12/22/2023 at 30 at lines 4-6, 31 at lines 2-4, 33 at lines 5-10).
“For treating or preventing a disease or condition caused by….” at the preamble is interpreted per MPEP § 2111.02, and is understood to be a “statement of the intentional purpose for which the method must be performed”, and further define the patient population of “subject in need thereof” (see, e.g., MPEP § 2111.02(II); see also Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333-34, 68 USPQ2d 1154, 1158 (Fed. Cir. 2003), explaining that in a claim directed to a method of treating or preventing a disease by administering a compound to "a human in need thereof," the court held that the preamble is a statement of the intentional purpose for which the method must be performed, and therefore the claim was properly interpreted to mean that the compound must be administered to a human with the recognized need identified in the preamble). Accordingly, the preamble is presumed in the instant claim to require that the compound must be administered to a subject having a recognized need for “treating or preventing a disease or condition caused by” any of the following diseases, conditions, cell types, and genera of illnesses:
…senescent cells, scarred cells, and/or cancer cells; age-related diseases; kidney disease; non-alcoholic steohepatitis (NASH) / non-alcoholic fatty liver diseases (NAFLD); liver fibrosis; idopathic pulmonary fibrosis (IPF); amyotrofic lateral sclerosis (ALS); osteoarthritis; COPD; musculoskeletal diseases; reductions of cognitive functions; or cancer…
(see, e.g., instant claim 24; see also Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10).
Accordingly, the enumerated cell types, diseases, conditions, and genera of illnesses are not required to be present per se in a patient, but rather only “a disease or condition caused by” the enumerated cell types, diseases, conditions, and genera of illnesses is required to be treated. However, “caused by” requires knowledge of causation4 (i.e., a functional limitation of origin) but the specification fails to provide a clear description of diseases and conditions “caused by” such diseases, conditions, cell types, and genera of illnesses. Per the disclosure, it is understood that the claim scope literally encompasses prevention of Alzheimer’s, Parkinson’s disease, Hutchinson Gilford’s progeria, diabetes, and all possible cancers (see, e.g., Spec. filed 12/22/2023 at 31 at lines 1-20) and presumably even greying hair (see, e.g., Spec. filed 12/22/2023 at 38 at lines 4-7). And although it is reasonably understood that “cancer” is “caused by” (directly or indirectly) “cancer cells” (consistent with the originally elected species), it is less clear what “disease or condition” may be “caused by” senescent cells, “reductions of cognitive functions”, “musculoskeletal diseases”, etc. Therefore, it is unclear what patients do or do not reasonably qualify as a “subject in need thereof” for purposes of the instant claim scope (see, e.g., MPEP § 2111, noting that claims are “given their broadest reasonable interpretation”). For purposes of applying prior art, a “subject in need thereof” is any patient in need of “treating or preventing” any cognizable disease or condition “caused by” any of the recited cell types, diseases, conditions, and genera of diseases, which is understood to cover at least all subjects having (or at risk of having) at least any type of cancer, kidney disease, non-alcoholic steohepatitis (NASH), non-alcoholic fatty liver diseases (NAFLD), liver fibrosis, idiopathic pulmonary fibrosis (IPF), amyotrophic lateral sclerosis (ALS), osteoarthritis, COPD, musculoskeletal diseases, age-related diseases (e.g., reduced milk production, pulmonary hypertension, epidermal thinning, atherosclerosis, lung emphysema, diabetic ulcers, renal disease, kyphosis, osteoporosis, macular degeneration, insulin resistance, diabetes, obesity, laminopathies, Hutchinson Gilford’s progeria, hernia, sarcopenia, cachexia, arthritis, scoliosis, cancer5), or reductions of cognitive functions (e.g., Alzheimer’s, Parkinson’s disease6), because such patients would have (or be at risk of having) any disease or condition “caused by” such conditions.
“Administering” is not defined or limited in the pending claim scope. It is understood to include at least intravenous administration routes per the originally elected species.
“Effective amount” is undefined on record and no guidance on general dosages, dosage formulations, or dosage frequencies required to be “effective” is disclosed in the originally filed disclosure. At best, it is understood to include 2.5 mg/kg of CL04183 (SEQ ID NO: 55) per the originally elected species, which is effective to treat colorectal cancer. However, zero guidance is provided for the treatment of non-colorectal cancers, NASH, ALS, NADLD, COPD, diabetes, Hutchinson Gilford’s progeria, etc., etc., which has necessitated a rejection under 35 USC 112, as set forth below.
For purposes of the instant examination, because claim 24 (i.e., the elected invention of a method of treatment) recites a “pharmaceutical composition according to claim 22”, this reference is construed to incorporate by reference all the limitations of claim 22 into instant claim 24 (see, e.g., MPEP § 608.01(n); see 35 U.S.C. §112(d)).
Additional claim interpretations are set forth below.
Claim Objections
Claim 24 is objected to because of the following informalities:
At claim 24, the acronym COPD should be completely spelled out at least once in the claim set.
At claim 25, the phrase “wherein said therapy is applied in senescent cells…..” is understood to depend from claim 24, which is an in vivo method, and should therefore read “wherein said therapy is applied to senescent cells…..”
At claim 25, the claim appears verbose and contains superfluous language, and language that lacks antecedent basis (see, e.g., Rejection below). Examiner suggests amending the claim to recite: “Claim 25. The method according to claim 24, wherein, prior to the administration of the pharmaceutical composition, the subject is pretreated with an anti-cancer chemotherapeutic agent”.
Appropriate correction is required.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show colors (i.e., red and blue) as described in the specification (see, e.g., Spec. filed 8/14/2022 at 39 discussing Figures 24-26, referring to lower and upper circles as red or blue). Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 24-25 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 24 recites an indefinite genus of “pharmaceutical composition according to claim 22”, and this reference is construed to incorporate by reference all the limitations of claim 22 into instant claim 24 (see, e.g., MPEP § 608.01(n); see 35 U.S.C. §112(d)). The genus at claim 24 is understood to incorporate all limitations at claim 22, but such recitations raise multiple issues of indefiniteness. For example, a “pharmaceutical composition according to claim 22” presumably includes “an amino acid sequence that is at least 70% identical to the amino acid sequence X3X2X4X5X7X5X4X4X6X18X8X3QNX9X8X10X10X11X12S*X13X14X11X11 (SEQ ID NO: 1), wherein each X is subsequently defined in a variable manner. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “identical” (i.e., “sequence identity”) used to define “pharmaceutical composition according to claim 22” at examined claim 24 is used to presumably mean an alignment of non-identical, variable positions to determine a percentage referred to as “identity”; while the accepted meaning of “percent identical”, “percent identity”, or “percent sequence identity” in the context of protein sequences refers to a relationship between two sequences following an optimal alignment, wherein the number of identical residues shared by two sequences are divided by the total length of one aligned sequence (see also, Spec. filed 8/14/2022 at 19 at 1st ¶). However, instant claim 1 attempts to capture the scope of any “amino acid sequence that is at least 70% identical to the amino acid sequence X3X2X4X5X7X5X4X4X6X18X8X3QNX9X8X10X10X11X12S*X13X14X11X11 (SEQ ID NO: 1), wherein each X is subsequently defined in a variable manner. This is problematic because it is unclear how sequence identity should be applied to the variable sequence of instant SEQ ID NO: 1, because sequence identity is not routinely defined for non-identical, variable sequences; for example, common algorithms (e.g., BLAST) do not align variable “X” residues as a match, but rather as a mismatch:
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92
678
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This means that simply attempting to align SEQ ID NO: 1 in a typical alignment algorithm (e.g., BLAST) would, at a maximum, yield only 2/25 matches (i.e., 12% identity based upon QN and S* in SEQ ID NO: 1). Accordingly, the art-recognized definition of sequence identity precludes the identification of any sequence sharing “at least 70%” sequence identity with instant SEQ ID NO: 1. Accordingly, the metes and bounds of compounds within the scope of a “pharmaceutical composition according to claim 22” is unknown, because the specification does not clearly redefine sequence identity to encompass the alignment of variable “X” positions as an “identical” match as illustrated above. For purposes of applying prior art, SEQ ID NO: 55 as present in the originally elected species is understood to fully satisfy the ambiguous structural requirements of instant claim 24.
Claim 24 recites an indefinite genus of “pharmaceutical composition according to claim 22”, and this reference is construed to incorporate by reference all the limitations of claim 22 into instant claim 24 (see, e.g., MPEP § 608.01(n); see 35 U.S.C. §112(d)). The genus at claim 24 is understood to incorporate all limitations at claim 22, but such recitations raise multiple issues of indefiniteness. For example, a “pharmaceutical composition according to claim 22” presumably includes “an amino acid sequence that is at least 70% identical to the amino acid sequence X3X2X4X5X7X5X4X4X6X18X8X3QNX9X8X10X10X11X12S*X13X14X11X11 (SEQ ID NO: 1), wherein each X is subsequently defined in a variable manner, which renders the pending claim scope indefinite per MPEP § 2173.05(b)(II). Per MPEP § 2173.05(b)(II), reference to a variable object may render a claim indefinite. Here, the definition of “pharmaceutical composition according to claim 22” is made with respect to a variable object, namely SEQ ID NO: 1, which is a sequence that is variable both in length and composition (i.e., multiple residues may be optionally “absent”). As noted in the preceding paragraph (incorporated herein), routine methods of determining % sequence identity are routinely utilized in the prior art to consider a variable “X” residue to be a mismatch:
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This raises a substantial question, namely “how and when should the limitation of ‘at least 70%’ sequence identity be applied?” Applying “sequence identity” to variable sequences yields different interpretations. For example, the percent identity may presumably imply that 70% of the positions of the total amino acids in SEQ ID NO: 1 may be altered or deleted. For example, seven positions of SEQ ID NO: 1 could be deleted or substituted by any amino acid (18/25>70%), or that ten additions could be made (i.e., 25/30 >70%). This interpretation would mean that sequences such as
X3X2X5X5X18X8X3X9X8X10X10X11X12S*X13X14X11X11
(i.,e., SEQ ID NO: 1 with seven deletions)
PPX4X5X7X5PPX6X18X8X3PPX9X8X10X10X11X12PX13X14X11X11
(i.e., SEQ ID NO: 1 with seven substituted prolines)
CX3X2CX4X5CX7X5CX4X4X6X18CX8X3QCNX9CX8CX10X10X11CX12S*X13X14CX11X11
(SEQ ID NO: 1, with ten added Cys residues sharing 25/30% identity)
would be included in the scope of instant claim 1. Alternatively, if the “at least 70%” sequence identity was applied to each individual sequence within the scope of instant claim 1 (i.e., approximately ~72,559,411,200 sequences7) (i.e., sequences sharing 70% sequence identity to SEQ ID NO: 9, 55, 60, etc. rather than SEQ ID NO: 1 as literally claimed), then this would yield a non-identical genus of sequences relative to the prior interpretation. This can be shown by inspecting SEQ ID NO: 1
X3X2X4X5X7X5X4X4X6X18X8X3QNX9X8X10X10X11X12S*X13X14X11X11
(SEQ ID NO: 1)
and then modifying it with seven initial deletions (i.e., yielding a sequence presumably having “at least 70%” sequence identity to instant SEQ ID NO: 1), which may yield a sequence such as
X3X2X4X5X18X8X3X9X8X10X10X11X12S*X13X14X11X11
(example of SEQ ID NO: 1 with 7 deletions)
If this example is then interpreted in view of the definitions of each “X”, and all residues that may be “optionally absent” are removed, we observe that the claim scope may encompass sequences such as
X4X5X18X8X8X11X11X11
(example of SEQ ID NO: 1 with 7 deletions and all optionally absent residues removed)
This interpretation is contrasted with the alternative approach of applying the “at least 70%” sequence identity limitations after selecting specific amino acids available at each position (i.e., with SEQ ID NOs: 9, 55, 60 etc., rather than SEQ ID NO: 1), because the two approaches lead to distinct, non-synonymous claim scopes. The difference may be highlighted by simply considering any comparable sequence of SEQ ID NO: 1 wherein all optionally absent positions are initially removed, which yields:
X4X5X7X5X4X4X6X18X8QNX8X11X11X11
(SEQ ID NO: 1, all optionally absent positions removed).
However, upon comparing
X4X5X18X8X8X11X11X11
(example of SEQ ID NO: 1 with 7 deletions and then all optionally absent residues removed)8
with
X4X5X7X5X4X4X6X18X8QNX8X11X11X11
(SEQ ID NO: 1, all optionally absent positions removed)9.
it is apparent that at best such sequences may at most only share 8/15 residues (i.e., ~53% identity). Accordingly, this illustrates that the order of applying “at least 70%” sequence identity impacts the resulting claim scope and meaning of a “pharmaceutical composition according to claim 22”. Because two or more reasonable interpretations exist, and no clarification is provided regarding how to apply sequence identity limitations to non-identical, variable positions, the claim scope is indefinite. For purposes of applying prior art, SEQ ID NOs: 55, present in the originally elected species, is presumed to fully satisfy the ambiguous structural requirements of instant claim 24.
Claim 24 recites an indefinite genus of “pharmaceutical composition according to claim 22”, and this reference is construed to incorporate by reference all the limitations of claim 22 into instant claim 24 (see, e.g., MPEP § 608.01(n); see 35 U.S.C. §112(d)). The genus at claim 24 is understood to incorporate all limitations at claim 22, but such recitations raise multiple issues of indefiniteness because the scope of “pharmaceutical composition according to claim 22” depends upon indefinite functional limitations set forth at claim 22. Claim 22 recites a genus ostensibly encompassing approximately ~72,559,411,200 or more sequences10, but then recites the “wherein” clause stating “wherein said compound induces apoptosis in senescent, scarred cells, and/or cancerous cells”, which renders the claim scope indefinite because it is unclear if (A) the “wherein” clause is a non-limiting recitation of an intended or expected result fully satisfied by all possible structures satisfying the positively recited structural limitations set forth in the body of claim 1 (see, e.g., MPEP § 2111.04(I)), or if (B) the “wherein” clause is a functional limitation that limits the scope of approximately ~72,559,411,200 or more sequences to a substantially narrower scope, like 50-100 sequences, or perhaps only SEQ ID NOs: 55. Accordingly, there are two potential interpretations that substantially alter the pending claim scope. Even assuming arguendo that the “wherein” clause is a functional limitation, the claim scope remains indefinite per MPEP § 2173.05(g), which explains that the use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. Here, the “wherein” clause does not correspond to any structure/function relationship of record permitting an artisan to reasonably identify which sequences from among the over 72,559,411,200 sequences ostensibly encompassed by instant claim 1 actually satisfy the ostensible functional limitation. Accordingly, the proper interpretation of the “wherein” clause directly impacts claim scope, and it is unclear how the “wherein” clause should be interpreted (i.e., functional language or non-limiting recitation of intended or expected results), and if it is a functional limitation, it is unclear what specific embodiments are included or excluded from the claim scope in the absence of a clear structure/function relationship. Accordingly, claim 24 recites an indefinite genus of “pharmaceutical composition according to claim 22”. For purposes of applying prior art, SEQ ID NOs: 55, present in the originally elected species, is presumed to fully satisfy the ambiguous structural requirements of instant claim 24.
Claim 24 recites and requires administration to a “subject in need thereof”, which renders the claim scope indefinite because it is unclear how to meaningfully identify what patients are included or excluded by this limitation. More specifically, claim 24 currently recites a method “for treating or preventing a disease or condition caused by….” at the preamble, which is interpreted per MPEP § 2111.02, and is understood to be a “statement of the intentional purpose for which the method must be performed”, and further define the patient population of “subject in need thereof” (see, e.g., MPEP § 2111.02(II); see also Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333-34, 68 USPQ2d 1154, 1158 (Fed. Cir. 2003), explaining that in a claim directed to a method of treating or preventing a disease by administering a compound to "a human in need thereof," the court held that the preamble is a statement of the intentional purpose for which the method must be performed, and therefore the claim was properly interpreted to mean that the compound must be administered to a human with the recognized need identified in the preamble). Accordingly, the preamble is presumed in the instant claim to require that the compound must be administered to a subject having a recognized need for “treating or preventing a disease or condition caused by” any of the following diseases, conditions, cell types, and genera of illnesses:
…senescent cells, scarred cells, and/or cancer cells; age-related diseases; kidney disease; non-alcoholic steohepatitis (NASH) / non-alcoholic fatty liver diseases (NAFLD); liver fibrosis; idopathic pulmonary fibrosis (IPF); amyotrofic lateral sclerosis (ALS); osteoarthritis; COPD; musculoskeletal diseases; reductions of cognitive functions; or cancer…
(see, e.g., instant claim 24; see also Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10). However, “caused by” requires foreknowledge of causation11 (i.e., a functional limitation of origin) but the specification fails to provide a clear description of diseases and conditions “caused by” such diseases, conditions, cell types, and genera of illnesses. Although it is reasonably understood that “cancer” is “caused by” (directly or indirectly) “cancer cells” (consistent with the originally elected species), it is less clear what “disease or condition” may be “caused by” senescent cells, “reductions of cognitive functions”, “musculoskeletal diseases”, etc., etc., and little clarifying guidance is provided in the originally filed disclosure. Accordingly, it is unclear if a subject with conditions such as greying hair, wrinkles, male pattern baldness, schizophrenia, dementia, gingivitis, tooth decay, gout, vision loss, hearing loss, eczema, coughing, etc., etc. are included or excluded from the claim scope. Notably, “death” is literally a “condition caused by” cancer, but it is unclear if the claim scope should reasonably be interpreted, literally, as claiming a method of “preventing” death, which seems unreasonable and fantastic. Accordingly, it is unclear what patients do or do not reasonably qualify as a “subject in need thereof” for purposes of the instant claim scope (see, e.g., MPEP § 2111, noting that claims are “given their broadest reasonable interpretation”). For purposes of applying prior art, a “subject in need thereof” is any patient in need of “treating or preventing” any cognizable disease or condition “caused by” any of the recited cell types, diseases, conditions, and genera of diseases, which is understood to cover at least all subjects having (or at risk of having) at least any type of cancer, kidney disease, non-alcoholic steohepatitis (NASH), non-alcoholic fatty liver diseases (NAFLD), liver fibrosis, idiopathic pulmonary fibrosis (IPF), amyotrophic lateral sclerosis (ALS), osteoarthritis, COPD, musculoskeletal diseases, age-related diseases (e.g., reduced milk production, pulmonary hypertension, epidermal thinning, atherosclerosis, lung emphysema, diabetic ulcers, renal disease, kyphosis, osteoporosis, macular degeneration, insulin resistance, diabetes, obesity, laminopathies, Hutchinson Gilford’s progeria, hernia, sarcopenia, cachexia, arthritis, scoliosis, cancer12), or reductions of cognitive functions (e.g., Alzheimer’s, Parkinson’s disease13), because such patients would have (or be at risk of having) any disease or condition “caused by” such conditions if they did, in fact, have the condition.
Claim 24 recites and requires administration of an “effective amount” of an unspecified but variable compound for the treatment of an unspecified and variable disease or condition using an unspecified but variable route of administration and patient population, which renders the pending claim scope indefinite. Accordingly, what does nor does not constitute an “effective amount” is a functional limitation that would depend upon the disease or condition actually treated, patient parameters (age, weight, health, etc.), route of administration (e.g., injection, inhalation, oral, sublingual injection, intraocular, etc.), actual compound used (e.g., one of the trillions of compounds within the scope of claim 22), etc. This is problematic because it is prima facie unknown what “amounts” are included or excluded by the pending claim scope. Per MPEP § 2173.05(g),
[T]he use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. . .
Here, the claims merely recite a description of functions or results to be achieved by the invention rather than a description of the structures capable of achieving the desired functions, and therefore the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what amounts do or do not infringe upon the scope of claim 24. As noted above, an “effective amount” varies depending upon multiple unspecified factors, which means the interpretation may vary from artisan to artisan, patient to patient, compound to compound, and disease to disease. This renders the claim scope indefinite (see, e.g., MPEP § 2173.05(b)). Accordingly, the metes and bounds of claim 24 is indefinite due to the usage of ill-defined, but variable functional limitations, such as “effective amounts”.
Claim 25 attempt to define a subgenus of compounds having unknown structural metes and bounds by reciting a function that the desired compounds are supposed to achieve (i.e., “anti-cancer chemotherapeutic agents or other standard of care drugs for the respective disease or condition”) but it is unclear what the “standard of care drugs” are for the ambiguous diseases and conditions “caused by” the recited cell types, diseases, conditions, and genera of diseases recited at claim 24 (see preceding rejections, noting that it is unclear what diseases and conditions are included or excluded from the claim scope). Accordingly, the language at claim 25 is indefinite because it amounts to a genus of unknown compounds that are functionally defined by reference to an unknown and variable “disease or condition”, but such language fails to correspond to structure/function relationship of record, commensurate in scope with the claims. Per MPEP § 2173.05(g),
[T]he use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. . .
Here, the claims merely recite a description of functions or results to be achieved by the invention rather than a description of the structures capable of achieving the desired functions, and therefore the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what compounds do or do not infringe upon the scope of claim 25. Although it is reasonably assumed that the limitations of claim 25 may be fully satisfied by anti-cancer chemotherapeutics in cancer patients, zero additional guidance or structure/function teachings are presented identifying any “standard of care drugs” for all other diseases and conditions encompassed by claim 24. Notably, the courts have stated that
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Accordingly, because it is unclear what compounds do or do not satisfy the functional limitations of claim 25, and an artisan would be unable to identify infringing from non-infringing compounds, claim 25 is rejected as indefinite.
Claim 25 recites the limitation "said therapy" at line 1. There is insufficient antecedent basis for this limitation in the claim. For purposes of applying prior art, claim 25 is understood to require pretreatment of the subject at claim 24 with an anti-cancer chemotherapeutic agent or “other standard of care drug” prior to the administration required by claim 24.
Claims 25 depends from an indefinite base claim and fail to clarify the indefinite issues of the base claim. Accordingly, these dependent claims are rejected for the reasons applied to the independent claim.
Claims 24-25 are rejected.
Claim Rejections - 35 USC § 112(a), Written Description
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 24-25 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.
Brief Statement of the Issue(s)
The pending claims encompass an essentially infinite variety of methods of treating unknown diseases or conditions, functionally defined as “caused by” any one of various sources, by administering (via any possible route of administration), an ill-defined and generally unknown “pharmaceutical composition according to claim 22”, to a subject, at an unknown and ill-described “effective amount”. In effect, the claim scope appears to broadly attempt to claim a panacea-type method, but without objective proof or even clear identification of structures and dosages capable of achieving statistically significant results.
Accordingly, the claims attempt to claim subject matter that was not described in a manner that reasonably establishes that the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim Scope
Claims 22 and 24 are representative of the pending claims scope because claim 24 recites and requires a “pharmaceutical composition according to claim 22”.
Regarding the structures of a “pharmaceutical composition according to claim 22”, claim 22 recites “an amino acid sequence that is at least 70% identical to the amino acid sequence X3X2X4X5X7X5X4X4X6X18X8X3QNX9X8X10X10X11X12S*X13X14X11X11 (SEQ ID NO: 1), wherein SEQ ID NO: 1 reads upon over ~72,559,411,200 L-amino acid sequences14, plus >72,559,411,200 D-amino acid sequences (see, e.g., claims 1(ii) and 22(ii)), plus >145,000,000,000 retro-inverso sequences of all L- and D- amino acid sequences claimed (see, e.g., claims 1(iii) and 22(iii)), plus all sequences sharing only “70%” sequence identity to such sequences (~potentially >>trillions of sequences). Accordingly, the claim scope is ostensibly vast and highly varied as no common structural motif is actually required to be present. Presumably, the genus of claim 22 is further limited by functional limitations recited at claim 22, which further limit the genus of >>trillions of sequences to a narrower subgenus of only those capable of “induc[ing] apoptosis in senescent, scarred cells, and/or cancerous cells” (see claim 22); however, this functional limitation does not correspond to a structure/function relationship of record.
Regarding the diseases and conditions treatable, claim 24 has been rejected under 35 USC 112(b) above, and those discussions are incorporated into the instant rejection. In brief, the preamble of claim 24 is presumed in the instant claim to require that the compound must be administered to a subject having a recognized need for “treating or preventing a disease or condition caused by” any of the following diseases, conditions, cell types, and genera of illnesses:
…senescent cells, scarred cells, and/or cancer cells; age-related diseases; kidney disease; non-alcoholic steohepatitis (NASH) / non-alcoholic fatty liver diseases (NAFLD); liver fibrosis; idopathic pulmonary fibrosis (IPF); amyotrofic lateral sclerosis (ALS); osteoarthritis; COPD; musculoskeletal diseases; reductions of cognitive functions; or cancer…
(see, e.g., instant claim 24; see also Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10). However, “caused by” requires foreknowledge of causation15 (i.e., a functional limitation of origin) but the specification fails to provide a clear description of diseases and conditions “caused by” such diseases, conditions, cell types, and genera of illnesses.
Regarding the “effective amount” administered to patients, claim 24 recites and requires administration of an “effective amount” of an unspecified but variable compound for the treatment of an unspecified and variable disease or condition using an unspecified but variable route of administration and patient population, which renders the pending claim scope indefinite. An “effective amount” is undefined on record and no guidance on general dosages, dosage formulations, or dosage frequencies required to be “effective” is disclosed in the originally filed disclosure.
The applicable claim interpretations have been set forth above in preceding rejections, and those interpretations are incorporated into the instant rejection.
Actual Reduction to Practice
Claims 24-25 are limited to in vivo administration methods wherein a disease or condition is treated. One species of in vivo administration method was reduced to practice, and is described at Figures 18-21 and page 42 of the originally filed disclosure (see, e.g., Spec. filed 12/22/2023 at 42 at lines 14-27). More specifically, the single species reduced to practice is understood to be a method wherein male mice were implanted with human CRC29 colorectal cancer organoids containing firefly luciferase, which formed a primary tumor, received carpofen 30 minutes before surgery and the day after, and then 14 days after transplantation, the mice were sedated using isoflurance, injected with 50 mg/kg ‘5-Fluorouracil (5-FU) by i.p. injection, and then seven days later, administered CL04183 (e.g., SEQ ID NO: 5516) via parenteral (i.v.) injection at 2.5 mg/kg at day 0, and then administration of CL04183 was repeated 2 and 4 days later (see, e.g., Spec. filed 12/22/2023 at 42 at lines 14-27).
Zero compounds other than CL04183 (e.g., SEQ ID NO: 55) were tested or reduced to practice.
Zero “effective amounts” other than 2.5 mg/kg at day 0, 2, and 4 of CL04183 (e.g., SEQ ID NO: 55) in male mice implanted with CRC29 colorectal cancer were reduced to practice.
Zero subjects other than male mice were reduced to practice.
Zero routes of administration other than i.v. injection were reduced to practice.
Zero diseases or conditions other than colorectal cancer and grey hair were reduced to practice (see, e.g., Figure 18, alleging that SEQ ID NO: 55 reduced grey hair in naturally aged mice). Notably, no statistically significant data is provided supporting the allegation of reduced grey hair (see, e.g., instant Fig. 18).
Zero evidence of statistically significant outcomes relative to controls was shown (see, e.g., Spec. filed 12/22/2023 at 42 at lines 14-27; Figures 18-21, noting that no test of statistical significance was identified on record, and statistical significance is actually identified).
Zero d-amino acid sequences appear to have been tested or reduced to practice.
Zero species having “staples” were reduced to practice and shown to have activity.
Zero “DRI” or D-retro-inverso isoforms appear to have been tested or reduced to practice.
Zero species lacking 100% sequence identity to instant SEQ ID NO: 55 were tested and shown to have any in vivo effect.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In this case, the claims ostensibly recite and encompass methods of treating numerous and ill-defined “diseases and conditions”, by administering (via numerous possible administration routes), an unknown “effective amount”, of over ~72,559,411,200 L-amino acid sequences, plus >72,559,411,200 D-amino acid sequences (see, e.g., claims 1(ii) and 22(ii)), plus >145,000,000,000 retro-inverso sequences of all L- and D- amino acid sequences claimed (see, e.g., claims 1(iii) and 22(iii)), plus all sequences sharing only “70%” sequence identity to such sequences (~potentially >>trillions of sequences). Accordingly, the claims are ill-defined, ill-described, but obviously vast and highly varied.
Although the claims encompass >>trillions of methods of in vivo treatment, the application appears to reduce to practice one species of in vivo methodology, wherein one peptide was administered by one route of administration to one type of subject having one type of cancer at one “effective” dosage, dosage frequency, and dosage formulation, and zero statistically significant results were shown using any disclosed statistical analysis.
Although the MPEP does not define what constitutes a sufficient number of representative species, the Courts have indicated that the disclosure of two species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Similarly, the disclosure of one species of the claimed method, using one peptide at one dosage, in one animal model of one type of cancer, without evidence of a statistically significant effect, does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus of >>trillions of species lacking any common feature with the single disclosed species.
Accordingly, the instant claims are directed to >>trillions of in vivo methods cannot be said to be not reasonably described by one highly specific species of in vivo method.
Identifying characteristics of the genus
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Regarding compounds, the disclosure is understood to provide an indefinite, laundry list disclosure of trillions of sequences represented by instant claims 22 and 24, which Applicant hopes will have activities and utilities sufficient to effect treatment and diagnosis of numerous diseases (see, e.g., Spec. filed 12/22/2023 at 4-6, claim 22). No significant, common, and required structural motif shared by all functional sequences was taught or disclosed by the specification. The disclosure and original claims fail to rectify or clarify what structures are actually encompassed by indefinite references at claims 22 and 24. This is pertinent because the courts have stated
“Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.”
University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Here, the Applicant has failed to “provide a description” of the claimed compound sufficient to distinguish infringing compounds from non-infringing compounds, and therefore an artisan would not reasonably conclude that the description establishes possession of the claimed invention.
Regarding “diseases and conditions” treated, the disclosure is understood to provide an indefinite, laundry list disclosure of numerous conditions and diseases that the invention can allegedly treat or prevent (see, e.g., Spec. filed 12/22/2023 at 31-33, claim 24). However, this is understood to be a list of what Applicant hopes one or more structures will be capable of achieving (see id), but such hoped-for and desired applications are unsupported by objective evidence. No statistically significant activity in vivo is actually shown, and such recitations are understood to be hypothetical in nature.
Regarding the “effective amount” administered to patients, claim 24 recites and requires administration of an “effective amount” of an unspecified but variable compound for the treatment of an unspecified and variable disease or condition using an unspecified but variable route of administration and patient population, which renders the pending claim scope indefinite. Unfortunately, an “effective amount” is undefined on record and no guidance on general dosages, dosage formulations, or dosage frequencies required to be “effective” for any particular sequence, route of administration, patient population, or disease or condition has actually been disclosed in the originally filed disclosure.
Accordingly, the ill-described genus and ill-defined functional limitations set forth in the pending claims, which are utilized to define the claimed genus, amounts to a vague attempt to capture trillions of ill-described in vivo methods of administering an unspecified and unknown “effective amount” of an unspecified and highly variable “compound” to treat a highly variable but unknown “disease or condition” using a variable route of administration and unspecified patient population. Accordingly, in the absence of an unambiguous structure/function relationship permitting an artisan to identify, a priori, which exact structures do or do not satisfy the functional limitations at issue; and an unambiguous structure/function relationship permitting an artisan to identify an “effective” and non-effective amount for a particular compound, patient population, and disease or condition to be treated, the disclosure fails to provide a meaningful definition and description of the genus of methods presently claimed.
Predictability in the Art
Although the level of skill in the art is high, the predictability in the art is low due to the complexity of biological systems, biochemistry, impact of peptide modifications (e.g., PEGylation, D-amino acids, retro-inverso approaches, etc.), impact of patient populations (age, sex, weight, health, height, etc.), etc. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of any guidance or consensus structures exactly what compounds are included or excluded by the recited genus of methods of claim 24, or otherwise known what amount of any particular compound would be “effective” to treat any particular disease or condition as presently claimed.
In addition, it is noted that the state of the art would reasonable suggest that Applicant did not describe the claimed invention sufficient to evidence possession in view of the prior art.
For example, the originally filed disclosure does not test or identify which D-amino acid sequences actually are capable of having any activity, and zero D-amino acid sequences within the scope of claims 22 and 24 appear to have actually been tested. This is relevant because the prior art of Li et al.17 teaches that
Despite their limited success as antigenic mimicry, retro-inverso isomers generally fail to emulate the protein-binding activities of their parent peptides…..Our findings reinforce that the retro-inverso strategy works poorly….
(see, e.g., Li at abs).
…retro-inverso isomers are significantly inferior to their parent L-peptides ….
(see, e.g., Li at 19580 at col I at 2nd full ¶).
Accordingly, one of skill in the art would not reasonably assume that retro-inverso sequences would necessarily work in the absence of any objective supporting evidence because an artisan would readily appreciate the general uncertainty and unpredictable nature of such modifications, and appreciate that such modification “generally fail”. The disclosure provides no guidance permitting an artisan to distinguish functional and non-functional retro-inverso sequences.
In addition, presumably the pending claim scope includes “treating” (which appears to be defined and described to include “preventing”)18 and “preventing” diabetes, cancer-related illnesses, all age-related illnesses (e.g., dementia, epilepsy, Alzheimer’s), all forms of cancers, etc. (see, e.g., Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10, 31-33, claim 24). However, the art teaches that numerous such diseases and conditions are not preventable. For example, not all forms of diabetes are preventable, curable, or capable of being “eliminated” as presently claimed (see, e.g., Mayo19 at 1-2 at § Overview, 11 at § Prevention, explaining that “There’s no known way to prevent type 1 diabetes”). Chemotherapy-induced peripheral neuropathy (“CIPN”) is a condition “caused by” cancer and treatments thereof (see, e.g., Starobova20 at title, abs), characterized by burning, stabbing, lancing, or shooting pains. Starobova discloses that “the development of CIPN is currently not preventable” (see Starobova at 2 at col I at 2nd ¶). The art teaches that “there is no effective treatment or proven prevention for Alzheimer’s and related dementias” (see, e.g., Dementia_Prevention21 at 3 and 6). Epilepsy risk increased with age, and therefore it is understood to be an “age-related illness”, but the art teaches that “Idiopathic epilepsy can not be prevented” (see, e.g., ADA22 at 8). Cancers, age, and illness are known to lead to depression and therefore fairly characterized as “caused by” such diseases or conditions, but regarding depression, “Most experts think it can’t be prevented” (see, e.g., Sacks23 at 1). Regarding cancers, many cancers cannot be prevented; for example “[t]here is no sure way to prevent pancreatic cancer” (see, e.g., ACS_Pancreas24 at 2); and “[t]here’s no known way to prevent most gallbladder cancers” (see, e.g., ACS_Gallbladder25 at 2). These examples are not exhaustive. Accordingly, an Artisan would not reasonably believe or conclude that such preventative methods credibly existed in the absence of objective, supporting evidence.
Accordingly, in the absence of sufficient structure/function teachings and clear descriptions of compounds permitting artisans to identify and distinguish infringing from non-infringing sequences, distinguish functional and non-functional sequences, identify treatable or preventable diseases or disorders, identify “effective” and not “effective” dosages of particular compounds for particular diseases, etc. commensurate in scope with the instant claims, an artisan would not reasonably conclude that Applicant possessed the full scope of the broad and highly varied claim scope.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). The courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789).
Regarding the ill-defined compounds at claims 24 and 25, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus comprising an unknown number of species defined by reference to one or more functional limitations and an ill-defined genus; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope. This also means that it is prima facie unclear what structures are infringe or do not infringe upon the pending claim scope.
Regarding the “effective amount” as claimed, the courts have held that a claim to a therapeutic method requiring administration of an “effective” amount of a compound at specific dosage range set forth in the disclosure for the treatment of a broad array of disorders failed to satisfy the Written Description Requirement because the disclosure addressed only “basic research and broad []dosage ranges”, but did not establish possession of a “therapeutically effective [] dose at the time of filing” (see, e.g., Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1343, 2021 U.S.P.Q.2d 1170, 2021 BL 455178, at *8 (Fed. Cir. 2021). The court clarified that although
An inventor need not "prove that a claimed pharmaceutical compound actually achieves a certain result. But when the inventor expressly claims that result, our case law provides that [such] result must be supported by adequate disclosure in the specification.”
See Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1343 (Fed. Cir. 2021).
The court further explained that
That Biogen later established the therapeutic efficacy of [a known compound at a specific dosage] is of no import to the written-description analysis. What matters for purposes of the inquiry [*1344] in this case is whether, at the time of filing the disclosure—well before the Phase III study even commenced—a skilled artisan could deduce simply from reading the specification that [a known compound at a specific dosage] would be a therapeutically effective treatment for MS. As to this point, the specification's focus on drug discovery and basic research further buttresses the district court's conclusion that the specification lacks an adequate written description to support the [] claims. . . . the law is clear that a patent cannot be awarded for mere theoretical research without more, see Ariad, 598 F.3d at 1353 . The written-description requirement limits patent protection only to individuals who perform the difficult work of producing a complete and final invention featuring all its claimed limitations and publicly disclose the fruits of that effort.
See Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1344, 2021 U.S.P.Q.2d 1170, 2021 BL 455178, at *9 (Fed. Cir. 2021); emphasis added
Here, like in Biogen, the Specification is directed to basic research without clear clinical data sharing a nexus with the claims because zero embodiments of the claimed invention were actually reduced to practice or discussed with specificity other than the usage of SEQ ID NO: 55 in a colorectal cancer model at 2.5 mg/kg via i.v. injection. Furthermore, unlike Biogen, here the claims further attempt to draw a fence around the treatment of all possible species of any “disease or condition caused by…” various cell types, diseases, conditions, and genera of illnesses, using numerous indefinite structures at any possible “effective” concentrations, via all possible routes of administration, in all possible patient populations. Therefore, the instant claims are substantially broader in scope than the claims of Biogen, but the disclosure of the instant Specification appears to provide substantially less guidance than that of the specification at issue in Biogen. Therefore, like Biogen, the instant claims lack written description support because an artisan “simply from reading the specification” could not deduce which compound at what concentration would be “effective” for the treatment of any particular “disease or condition” as presently claimed.
In conclusion, for the reasons discussed above, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Accordingly, claims 24 and 25 are rejected.
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 24-25 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 colorectal cancer by administering ‘5-FU in combination with SEQ ID NO: 55 via parenteral (i.v.) injection at 2.5 mg/kg at days 0, 2, and 426, does not reasonably provide enablement for preventing any diseases or conditions within the scope of claim 24. 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: The scope of claims 24-25 have been discussed in preceding rejections under 35 USC 112(a), 112(b), and in a separate claim interpretation section, and those discussions are incorporated into the instant rejection. In brief, claims 24-25 are directed to methods of preventing numerous diseases and conditions by administering unspecified compounds at an unspecified “effective amount” to a “patient in need thereof”. Accordingly, the claim scope is vast and highly varied.
Brief introduction of the issue: The enablement provided is not commensurate in scope with the claims because the claims read upon prevention of numerous diseases and conditions, which are not recognized as preventable by artisans, including for example, diabetes, cancer-related illnesses, all age-related illnesses (e.g., dementia, epilepsy, Alzheimer’s), all forms of cancers, etc. (see, e.g., Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10, 31-33, claim 24).
The amount of direction or guidance presented and the existence of working examples: The originally filed disclosure discloses one example with specificity, namely one species of in vivo administration method, which is described at Figures 18-21 and page 42 of the originally filed disclosure (see, e.g., Spec. filed 12/22/2023 at 42 at lines 14-27). More specifically, the single species reduced to practice is understood to be a method wherein male mice were implanted with human CRC29 colorectal cancer organoids containing firefly luciferase, which formed a primary tumor, received carpofen 30 minutes before surgery and the day after, and then 14 days after transplantation, the mice were sedated using isoflurance, injected with 50 mg/kg ‘5-Fluorouracil (5-FU) by i.p. injection, and then seven days later, administered CL04183 (e.g., SEQ ID NO: 5527) via parenteral (i.v.) injection at 2.5 mg/kg at day 0, and then administration of CL04183 was repeated 2 and 4 days later (see, e.g., Spec. filed 12/22/2023 at 42 at lines 14-27). Zero examples of statistically significant results were disclosed on record, and zero examples showing prevention of any disease or condition was disclosed on record. Zero guidance regarding the “effective amount” of any compound sufficient to prevent any disease was disclosed or reduced to practice with specificity. Accordingly, no objective supporting evidence correlating any “effective amount” with the complete prevention of any disease or disorder within the scope of instant claims 24-25 was disclosed on record.
The state of prior art: The lack of guidance and working examples is pertinent because the pending claim scope includes “treating” (which appears to be defined and described to include “preventing”)28 and “preventing” diabetes, cancer-related illnesses, all age-related illnesses (e.g., dementia, epilepsy, Alzheimer’s), all forms of cancers, etc., etc. (see, e.g., Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10, 31-33, claim 24). However, the art teaches that numerous such diseases and conditions are not preventable. For example, not all forms of diabetes are preventable, curable, or capable of being “eliminated” as presently claimed (see, e.g., Mayo29 at 1-2 at § Overview, 11 at § Prevention, explaining that “There’s no known way to prevent type 1 diabetes”). Chemotherapy-induced peripheral neuropathy (“CIPN”) is a condition “caused by” cancer and treatments thereof (see, e.g., Starobova30 at title, abs), characterized by burning, stabbing, lancing, or shooting pains. Starobova discloses that “the development of CIPN is currently not preventable” (see Starobova at 2 at col I at 2nd ¶). The art teaches that “there is no effective treatment or proven prevention for Alzheimer’s and related dementias” (see, e.g., Dementia_Prevention31 at 3 and 6). Epilepsy risk increased with age, and therefore it is understood to be an “age-related illness”, but the art teaches that “Idiopathic epilepsy can not be prevented” (see, e.g., ADA32 at 8). Cancers, age, and illness are known to lead to depression and therefore fairly characterized as “caused by” such diseases or conditions, but regarding depression, “Most experts think it can’t be prevented” (see, e.g., Sacks33 at 1). Regarding cancers, many cancers cannot be prevented; for example “[t]here is no sure way to prevent pancreatic cancer” (see, e.g., ACS_Pancreas34 at 2); and “[t]here’s no known way to prevent most gallbladder cancers” (see, e.g., ACS_Gallbladder35 at 2). These examples are not exhaustive. Accordingly, an Artisan would not reasonably believe or conclude that such preventative methods credibly existed in the absence of objective, supporting evidence.
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 preventing unspecified diseases and conditions by administering an unknown “effective amount” of an unknown and unspecified compound 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, drug compositions, drug formulation, etc. Furthermore, as evidenced by the art discussed above, an artisan would readily appreciate that may diseases and conditions within the scope of instant claim 24 and 25 not art-recognized as “preventable” or even well-understood.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of treating various types of conditions using prodrugs were known in the art at the time of the invention, it was not routine in the art prevent all diseases and conditions encompassed by claims 24-25 commensurate in scope with the instant claims. Accordingly, in the absence of (i) a biochemical mechanism pertinent to all diseases and conditions, and/or (ii) objective evidence identifying that prevention of all diseases and disorders within the scope of instant claims 24-25 is even possible, one of skill in the art would not reasonable conclude that an unspecified compound used at an unspecified amount could prevent all possible diseases and conditions as presently claimed, in the absence of credible and substantial guidance. However, no such credible and substantial guidance has been set forth on record. Accordingly, to practice the full scope of the instant invention including 100% prevention of all diseases and disorders within the scope of instant claims 24-25, an artisan would be unduly burdened to actually identify an “effective” dose, administration route, and patient population (age, gender, weight, etc.), and compound structure actually capable of satisfying the requirements of claim 24-25 and capable of preventing such diseases and conditions; however, such a set of parameters may not actually exist or be possible as evidenced by the art cited and discussed above, which identifies that multiple diseases and disorders within the instant claim scope are viewed as unpreventable by artisans.
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 24-25 are rejected.
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 24-25 are rejected under 35 U.S.C. 102(a)(1)/(2) as being clearly anticipated by WO2016/118014A2 (De Keizer et al.; July 28, 2016; cited in IDS filed 12/29/2023 as cite No. 2).
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 24-25, WO’014 teaches and discloses a method wherein mice in need of treatment for senescence (i.e., a disease or condition “caused by” aging) were administered an anti-cancer chemotherapeutic agent, namely doxorubicin, and were then subsequently treated with 10 mg/kg “FOXO4 DRI” via intravenous injection four times (see, e.g., WO’014 at 20 at lines 14-20, Figure 4(F)-(G)). Additionally, WO’014 discloses a method wherein mice in need of treatment for senescence (i.e., a disease or condition “caused by” aging) were administered an anti-cancer chemotherapeutic agent, namely doxorubicin, and were then subsequently treated with 5 mg/kg “FOXO4 DRI” via intravenous injection three times with 1 day in between doses (see, e.g., WO’014 at 20 at lines 24-30, Figure 4(F)-(H)). Accordingly, the prior art discloses and reduces to practice a method for treating a condition caused by senescent cells and age-related diseases, in a subject in need thereof, wherein an effective amount (5 or 10 mg/kg) of the compound (“FOXO4 DRI”) was intravenously administered to the subject, and wherein the subject was pretreated with the anti-cancer chemotherapeutic agent of doxorubicin (see, e.g., WO’014 at 20 at lines 14-30, Figure 4(F)-(H)). Regarding instant claim 24 and a “pharmaceutical composition according to claim 22”, the compound of “FOXO4 DRI” utilized in the disclosed methods (see, e.g., WO’014 at 20 at lines 14-30, Figure 4(F)-(H)) is understood to have the structure
LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG
(see, e.g., WO’014 at 78 at lines 10-14, noting that all amino acids are D-amino acids; compare id. with instant SEQ ID NOs: 9 and 21, showing 100% sequence identity). This sequence is understood to satisfy the requirements of claims 22 wherein the sequence satisfies
X3-X2-X4-X5-X7-X5-X4-X4-X6-X18-X8-X3-QN-X9-X8-X10-X10-X11-X12-S*-X13-X14-X11-X11
Where, in order X3 is S, X2 is E, X4 is I, X5 is A, X7 is Q, X5 is S, X4 is I, X4 is L, X6 is E, X18 is A, X8 is Y, X3 is S, QN, X9 is G, X8 is W, X10 is A, X10 N, X11 is R, X12 is R, S* is S, X13 is G, X14 is a mismatch of G, X11 is K, X11 is R, wherein the sequence shares 24/25 matches (i.e., presumably qualifies as 96% identity for purposes of this rejection) with instant SEQ ID NO: 1 (compare WO’014 at 78 at lines 10-14 and “FOXO4 DRI” with instant SEQ ID NOs: 1, 9, and 21, and claim 22).
Accordingly, claims 24-25 are rejected.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 24-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 12,653,86236. Although the claims at issue are not identical, they are not patentably distinct from each other as described below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Here, although the same invention is not being claimed twice (see, e.g., MPEP § 804(II)(A), discussing Statutory Double Patenting), a Nonstatutory Double Patenting rejection is appropriate because although the conflicting claims are not identical, at least one examined application claim is not patentably distinct from the reference claims because the examined application claim is either anticipated by, or would have been obvious over, the reference claims for the reasons set forth in the following paragraph[1]: Per MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences”. MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an obviousness analysis. Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
Regarding instant claims 24-25, US’862 recites and claims “a pharmaceutical composition for treating or preventing senescent cells in a subject”, wherein the composition may comprise at least originally elected species of SEQ ID NO: 55 (see, e.g., US’862 at claims 1-3).
The issued claims of US’862 differ from instant claims 24-25 as follows: Instant claims 24 is directed to a method achieving the intended use recited by US’862 of “treating or preventing senescent cells in a subject”, and differs only by statutory class as it is direct to a method rather than a product with an intended and expected use as claimed by US’862.
Critically, this difference does not render the two claim sets patentably distinct because species of the instantly claimed method amount to obvious variants of the issued claims (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”; see also US’862 at col. 28 at lines 29-49, addressing the originally elected species reading upon both claims 24-25). Therefore, the instant claims merely claim a particular use described in US’862 for the claimed compositions of the issued patent, and therefore such claims are not patentably distinct (see, e.g., Sun Pharmaceutical Industries, Ltd. v. Eli Lilly and Co., 625 F.3d 1319 (Fed. Cir. 2010)).
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious, claimed variant of the patent claims, namely the instant claims are directed to a named, claimed species set forth in the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 12137
As noted at MPEP § 804(II)(B)(4), the primary reference and the instant Application are understood to require only a one-way test for distinctiveness.
Accordingly, instant claims 24-25 are rejected.
Examiner Suggestions
Claim 24 could be amended to overcome multiple rejections of record, if limited to reflect the originally elected species, which was deemed free of the prior art. For example, claim 24 could be amended to recite
A combination therapy method for the treatment of colorectal cancer in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a first pharmaceutical composition comprising ‘5-Fluorouracil (5-FU); and then subsequently administering to said subject a second pharmaceutical composition comprising SEQ ID NO: 55.
Such an amendment, coupled with the (i) cancellation of claims 1-23 and 25 and a (ii) terminal disclaimer U.S. Patent No. 12,653,862, could place claim 24 in form for allowance.
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.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 AKIEAAILDAFSQNWRKRRRRQRRKKRG
2 SEQ ID NO: 55 does not unambiguously share “70%” sequence identity with instant SEQ ID NO: 1 as required by claim 22 (see rejections under 35 USC §112(b), below), but SEQ ID NO: 55 is reasonably inferred to read upon claim 24 by Applicant admission, wherein X3 is A, X2 is K, X4 is I, X5 is E, X7 is A, X5 is A, X4 is I, X4 is L, X6 is D, X18 is A, X8 is F, X3 is S, X9 is absent, X8 is W, X10 is absent, X10 is absent, X11 is R, X12 is absent, S* is absent, X13 is absent, X14 is absent, X11 is K, and X11 is R (yielding the truncated portion of SEQ ID NO: 55 of “AKIEAAILDAFSQNWRKR”).
3 AKIEAAILDAFSQNWRKRRRRQRRKKRG
4 See, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used in separate claims, a difference in meaning is presumed".
5 see, e.g., Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10.
6 see, e.g., Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10.
7 X3X2X4X5X7X5X4X4X6X18X8X3QNX9X8X10X10X11X12S*X13X14X11X11 (SEQ ID NO: 1), wherein each X is subsequently defined in a variable manner, such that X2 may be selected from 4 possibilities; X3 may be selected from 3 possibilities; X4 may be selected from 3 possibilities; X5 may be selected from 5 possibilities; X6 may be selected from 2 possibilities; X7 may be selected from 6 possibilities; X8 may be selected from 4 possibilities; X9 may be selected from 3 possibilities; X10 may be selected from 3 possibilities; X11 may be selected from 2 possibilities; X12 may be selected from 2 possibilities; X13 may be selected from 3 possibilities; X14 may be selected from 3 possibilities; and X18 may be selected from 2 possibilities; furthermore, claim 1 at (ii) encompasses all such sequences having 80-100% D-amino acid substitutions, and claim 1 at (iii) encompasses all retro inverso peptide sequences of both (i) and (ii). Acordingly, claim 1(i) appears to include ~72,559,411,200 sequences. This number would be doubled in view of claim 1(iii), which includes D- and L- reversed sequences of all sequences within the scope of claim 1(i) and 1(ii).
8 This represents a sequence wherein “70% sequence identity” is taken into account first, by forming a deletion variant of SEQ ID NO: 1, wherein seven random positions are deleted from SEQ ID NO: 1 prior to considering the definitions for each “X”.
9 This represents a sequence wherein “70% sequence identity” is taken into account second, after each “X” is considered. Here only optionally absent residues are accounted for prior to applying to “at least 70%” sequence identity limitation.
10 X3X2X4X5X7X5X4X4X6X18X8X3QNX9X8X10X10X11X12S*X13X14X11X11 (SEQ ID NO: 1), wherein each X is subsequently defined in a variable manner, such that X2 may be selected from 4 possibilities; X3 may be selected from 3 possibilities; X4 may be selected from 3 possibilities; X5 may be selected from 5 possibilities; X6 may be selected from 2 possibilities; X7 may be selected from 6 possibilities; X8 may be selected from 4 possibilities; X9 may be selected from 3 possibilities; X10 may be selected from 3 possibilities; X11 may be selected from 2 possibilities; X12 may be selected from 2 possibilities; X13 may be selected from 3 possibilities; X14 may be selected from 3 possibilities; and X18 may be selected from 2 possibilities; furthermore, claim 1 at (ii) encompasses all such sequences having 80-100% D-amino acid substitutions, and claim 1 at (iii) encompasses all retro inverso peptide sequences of both (i) and (ii). Acordingly, claim 1(i) appears to include ~72,559,411,200 sequences. This number would be doubled in view of claim 1(iii), which includes D- and L- reversed sequences of all sequences within the scope of claim 1(i) and 1(ii).
11 See, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used in separate claims, a difference in meaning is presumed".
12 see, e.g., Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10.
13 see, e.g., Spec. filed 12/22/2023 at 10 at lines 2-3, 10 at lines 5-10.
14 X3X2X4X5X7X5X4X4X6X18X8X3QNX9X8X10X10X11X12S*X13X14X11X11 (SEQ ID NO: 1), wherein each X is subsequently defined in a variable manner, such that X2 may be selected from 4 possibilities; X3 may be selected from 3 possibilities; X4 may be selected from 3 possibilities; X5 may be selected from 5 possibilities; X6 may be selected from 2 possibilities; X7 may be selected from 6 possibilities; X8 may be selected from 4 possibilities; X9 may be selected from 3 possibilities; X10 may be selected from 3 possibilities; X11 may be selected from 2 possibilities; X12 may be selected from 2 possibilities; X13 may be selected from 3 possibilities; X14 may be selected from 3 possibilities; and X18 may be selected from 2 possibilities; furthermore, claim 1 at (ii) encompasses all such sequences having 80-100% D-amino acid substitutions, and claim 1 at (iii) encompasses all retro inverso peptide sequences of both (i) and (ii). Acordingly, claim 1(i) appears to include ~72,559,411,200 sequences. This number would be doubled in view of claim 1(iii), which includes D- and L- reversed sequences of all sequences within the scope of claim 1(i) and 1(ii).
15 See, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used in separate claims, a difference in meaning is presumed".
16 AKIEAAILDAFSQNWRKRRRRQRRKKRG
17 Li et al., Limitations of peptide retro-inverso isomerization in molecular mimicry. J Biol Chem. 2010 Jun 18;285(25):19572-81. doi: 10.1074/jbc.M110.116814. Epub 2010 Apr 9. PMID: 20382735; PMCID: PMC2885236; hereafter “Li”; cited in IDS filed 10/28/2025 as cite No. 1.
18 See, e.g., Spec. filed 12/22/2023 at 33 at lines 1-4, stating that “treatment can also avoid (prevent)….”
19 Type 1 diabetes, Mayo Clinic, mayoclinic.org, attached as pdf, 15 pages, also available at https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011#:~:text=Prevention,one%20of%20these%20clinical%20trials (last visited 5/30/2025); hereafter “Mayo”; cited in previous action.
20 Starobova et al., Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy. Front Mol Neurosci. 2017 May 31;10:174. doi: 10.3389/fnmol.2017.00174. PMID: 28620280; PMCID: PMC5450696; hereafter “Starobova”.
21 “Can I Prevent Dementia?”, Alzheimers/gov, 24 pages, attached as pdf (April 1, 2025), also available at https://www.alzheimers.gov/life-with-dementia/can-i-prevent-dementia (last visited 10/15/2025); hereafter “Dementia_Prevention”.
22 “Generalized Seizure”, ada.com, 10 pages, attached as pdf (August 1, 2025), also available at https://ada.com/conditions/generalized-seizure/ (last visited 10/15/2025); hereafter “ADA”.
23 Sacks, “Can You Prevent Depression?”, webmd.com, 2 pages, attached as pdf (July 10, 2025), also available at https://www.webmd.com/depression/understanding-depression-prevention (last visited 10/15/2025); hereafter “Sacks”.
24 ] “Can Pancreatic Cancer Be Prevented?”, American Cancer Society, 5 pages, attached as pdf, (Feb 5, 2024), also available at https://www.cancer.org/cancer/types/pancreatic-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Pancreas”.
25 “Can Gallbladder Cancer Be Prevented?”, American Cancer Society, 4 pages, attached as pdf, (May 16, 2025), also available at https://www.cancer.org/cancer/types/gallbladder-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Gallbladder”.
26 see, e.g., Spec. filed 12/22/2023 at 42 at lines 14-27
27 AKIEAAILDAFSQNWRKRRRRQRRKKRG
28 See, e.g., Spec. filed 12/22/2023 at 33 at lines 1-4, stating that “treatment can also avoid (prevent)….”
29 Type 1 diabetes, Mayo Clinic, mayoclinic.org, attached as pdf, 15 pages, also available at https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011#:~:text=Prevention,one%20of%20these%20clinical%20trials (last visited 5/30/2025); hereafter “Mayo”; cited in previous action.
30 Starobova et al., Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy. Front Mol Neurosci. 2017 May 31;10:174. doi: 10.3389/fnmol.2017.00174. PMID: 28620280; PMCID: PMC5450696; hereafter “Starobova”.
31 “Can I Prevent Dementia?”, Alzheimers/gov, 24 pages, attached as pdf (April 1, 2025), also available at https://www.alzheimers.gov/life-with-dementia/can-i-prevent-dementia (last visited 10/15/2025); hereafter “Dementia_Prevention”.
32 “Generalized Seizure”, ada.com, 10 pages, attached as pdf (August 1, 2025), also available at https://ada.com/conditions/generalized-seizure/ (last visited 10/15/2025); hereafter “ADA”.
33 Sacks, “Can You Prevent Depression?”, webmd.com, 2 pages, attached as pdf (July 10, 2025), also available at https://www.webmd.com/depression/understanding-depression-prevention (last visited 10/15/2025); hereafter “Sacks”.
34 ] “Can Pancreatic Cancer Be Prevented?”, American Cancer Society, 5 pages, attached as pdf, (Feb 5, 2024), also available at https://www.cancer.org/cancer/types/pancreatic-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Pancreas”.
35 “Can Gallbladder Cancer Be Prevented?”, American Cancer Society, 4 pages, attached as pdf, (May 16, 2025), also available at https://www.cancer.org/cancer/types/gallbladder-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Gallbladder”.
36 The restriction requirement was withdrawn in the Notice of Allowance of App 17/799,675 mailed 2/20/2026 at pages 3-4
[1] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
37 The restriction requirement was withdrawn in the Notice of Allowance of App 17/799,675 mailed 2/20/2026 at pages 3-4; and the instant Application was not filed as a DIV.
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