DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 37, 39, 40, 47-48, 50-54, and 57 are pending. Claims 38, 40, 41, and 44 were canceled; claim 57 is newly added; and claims 37, 39, 40, and 50 were amended in the Reply filed 9/26/2025. Claims 51-54 remain withdrawn. Claims 37, 39-40, 47-48, 50, and 57 are presently considered.
Election/Restrictions
. Applicant’s election of the narrow subgenus of patentably indistinct species of method wherein the condition of dilated cardiomyopathy is treated or prevented in an unspecified subject by the administration of an unspecified amount of a “LINC complex inhibitor” via an unspecified route of administration, and wherein the “LINC complex inhibitor” is “a peptide/polypeptide” of unknown structure in the Reply filed December 9, 2024, was previously 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)).
In the Reply filed 9/26/2025, Applicant amended the claim scope to exclude the originally elected species, which required administration of a peptide/polypeptide to a subject (see, e.g., Reply filed Dec. 9, 2024 at 1; see also Action mailed 5/28/2025 at 2-3). Following the amendment filed 5/28/2025, the amended claims require administration of a nucleic acid to a subject.
Per MPEP § 803.02 and § 809.02, examination has been extended to a non-elected species corresponding to a nucleic acid encoding “SS-HASun1L-KDEL” administered to humans to treat laminopathies.
Following extensive search and examination, the non-elected species has been deemed obvious in view of the prior art, as applied below.
Claims 51-54 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 9, 2024.
During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below.
Claims 37, 39-40, 47-48, 50, and 57 are presently considered.
Priority
The priority claim to SG10201906637U (filed 7/17/2019) is acknowledged.
Information Disclosure Statement
The information disclosure statement filed 9/26/2025 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits1.
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 37 is representative of the pending claim scope and presently recites:
37. (Currently amended) A method of treating or preventing a laminopathy associated with mutation to LMNA in a human subject, comprising administering nucleic acid encoding a LINC complex inhibitor to a human subject having a laminopathy associated with mutation to LMNA in an amount sufficient to show thereapeutic or prophylactic benefit to the human subject;
wherein the LINC complex inhibitor is: (i) a dominant-negative SUN domain-containing protein that binds to a KASH domain-containing protein and thereby competitively inhibits interaction between an endogenous SUN domain-containing protein and an endogenous KASH domain-containing protein, or ([[i]]ii) a dominant-negative KASH domain-containing protein that binds to a SUN domain-containing protein and thereby competitively inhibits interaction between an endogenous SUN domain-containing protein and an endogenous KASH domain-containing protein; and
wherein the laminopathy associated with mutation to LMNA is not Hutchinson-Gilford Progeria Syndrome (HGPS).
Additional claim interpretations are set forth below. Examiner notes that the amendments exclude the direct administration of LINC complex inhibitors consisting of peptides, polypeptides, and proteins.
Regarding the preamble of claim 372, per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of claim 37 is understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”).
“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)).
Administration route: The claims do not recite nor require a particular administration route. Accordingly, the pending claims read upon oral, topical, sublingual, anal, retinal, vaginal, IV, intramuscular, subdermal routes, among numerous other routes of administration.
Dosage: The pending claim recites and requires administration of “an amount sufficient to show therapeutic or prophylactic benefit to the human subject”. This phrase is undefined on record or in the claims. For purposes of applying prior art, any amount of nucleic acid is reasonably inferred to be a “sufficient” amount.
Administered compound encoded by nucleic acid: A “LINC complex inhibitor” is understood to be functionally defined polypeptide capable of being encoded by a nucleic acid, wherein the “LINC complex inhibitor” is either
a dominant-negative SUN domain-containing protein that binds to a KASH domain-containing protein and thereby competitively inhibits interaction between an endogenous SUN domain-containing protein and an endogenous KASH domain-containing protein, or
a dominant-negative KASH domain-containing protein that binds to a SUN domain-containing protein and thereby competitively inhibits interaction between an endogenous SUN domain-containing protein and an endogenous KASH domain-containing protein.
These functional descriptions fail to meaningfully correspond to a structure/function relationship of record. Accordingly, the relevant issue is what exact structures set forth in the original disclosure or otherwise known in the prior art are actually sufficient to achieve the required structure/function relationship now claimed? For purposes of applying prior art, the functional descriptions are reasonably inferred to be fully satisfied by all structures encompassed by dependent claims 47 and 48 (i.e., claims 47-48 are presumed to satisfy 35 USC § 112(d)). Accordingly, the functional limitations defining a “LINC complex inhibitor” at amended claim 37(i) and 37(ii) are understood to be satisfied by at least any structure comprising or consisting of any amino acid sequence having at least 70% identity to either instant SEQ ID NO: 82 or 97, wherein these sequences have the following structures:
SEQ ID NO: 82
GGSILSTRCSETYETKTALMSLFGIPLWYFSQSPRVVIQPDIYPGNCWAFKGSQGYLVVRLSMMIHPAAFTLEHIPKTLSPTGNISSAPKDFAVYGLENEYQEEGQLLGQFTYDQDGESLQMFQALKRPDDTAFQIVELRIFSNWGHPEYTCLYRFRVHGEPV
SEQ ID NO: 97
RGFLFRVLRAALPLQLLLLLLIGLACLVPMSEEDYSCALSNNFARSFHPMLRYTNGPPPL
In addition, the Specification is reasonably understood to identify that “LINC complex inhibitors” also include sequences sharing at least 70% sequence identity to any one of SEQ ID NOs: 82-87, 97-101 or 114 (see, e.g., Spec. filed 1/13/2022 at 23 at line 34 to p. 24 at line 2, p. 24 at line 39 to p. 25 at line 8).
“Laminopathy associated with mutation to LMNA in a human subject” is understood to include at least the diseases set forth at claims 39, 40, and 57. This is consistent with the Specification, which identifies
…diseases which are "associated with" mutations to a given gene/genes are diseases which are caused or exacerbated by such mutations, or for which such mutations are a risk factor for the development or progression of the disease.
(see, e.g., Spec. filed 1/13/2022 at 45 at lines 1-5).
This is pertinent because the Specification also states
As used herein, a "laminopathy" is a disease/pathological condition associated with mutation to a gene encoding a lamin.
Genes encoding lamins include LMNA (which encodes lamins A and C), and LMNB1, LMNB2, which encode lamins B1 and B2. Accordingly, aspects of the present invention concern the treatment/prevention of diseases associated with mutation to LMNA, LMNB1 and/or LMNB2.
(see, e.g., Spec. filed 1/13/2022 at 45 at lines 29-35).
The instant disclosure identifies numerous laminopathies associated with mutations in LMNA (see, e.g., Spec. filed 1/13/2022 at 49 at line 29 to page 50 at line 25; see also instant claims 39, 40, and 57).
Patient population vs intended result: The patient population of amended claim 37 as filed 9/26/2025 is understood to be “a human subject having a laminopathy associated with mutation to LMNA” (see, e.g., claim 37 at line2-5), wherein the preamble recites a method “of treating or preventing a laminopathy associated with mutation to LMNA in a human subject”. Critically, the intended result of preventing and treating is not limited to the laminopathy present in the human subject; accordingly, the patient may have one laminopathy while being treated to treat or prevent a separate and distinct laminopathy.
Patient population: Amended claim 37 as filed 9/26/2025 requires administration to “a human subject having a laminopathy associated with mutation to LMNA”, wherein a “laminopathy associated with mutation to LNA” encompasses any human subject suffering from any condition enumerated at instant claims 39, 40, 57, or described in the originally filed disclosure a (see, e.g., Spec. filed 1/13/2022 at 49 at line 29 to page 50 at line 25). Accordingly, a human subject may have “aging”, “tooth disease”, “diabetes mellitus”, “heart disease”, “osteoporosis”, “skin disease”, “Muscle Tissue Disease”, “prolapse of the female genital organ”, etc. Notably, such broad genus of patients reasonably appears to include all humans since all humans age and no specific mutation to LMNA is identified (i.e., silent mutations are encompassed by the claim scope and “laminopathy” includes aging, and therefore presumably all humans are encompassed by the claim scope.
Claims 39, 40, and 57 each recite a “wherein” clause. Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Here, the “wherein” clause at each of dependent claims 39-40 and 57 do not unambiguously correspond to a clear structure/function relationship in the original disclosure, and therefore such “wherein” clauses are not functional limitations. Instead, the “wherein” clause is understood to merely recite an intended or expected result fully satisfied by the positively recited steps and/or structures set forth in the body of the claim. This is reasonable because the claim 37 is not limited to patients “in need thereof” or having a laminopathy, but rather claim 37 recites a method of administering compounds to any patients with the intended and expected result of “treating or preventing” any laminopathy recited at dependent claims 39-40. Therefore, the “wherein” clause of claims 38-40 are understood to be fully satisfied by all prior art embodiments that satisfy the active method steps of claim 37, namely the treatment of any subject by administering (via any route) any “LINC complex inhibitor” within the scope of claim 37, at any “effective amount”.
Potential negative proviso appears non-limiting in context: Claim 37 was amended to recite “wherein the laminopathy is not Hutchinson-Gilford Progeria Syndrome (HGPS)” at the last line of amended claim 37. This amendment has been rejected as indefinite for lack of antecedent basis in view of the most recent amendments (see rejections below). Per MPEP §§ 2111.02, 2111.04, and 2173.05(i), the relevant question is “how does this phrase change the pending claim scope?”. In brief, for purposes of Examination, the recitation continues to be understood consistent with the prior action, namely the negative proviso does not limit the patient population, but only limits and intended and expected result, as explained below: As explained above, the instant claims are directed to a prophylactic and preventative treatment of any human subject for any “laminopathy” recited at claims 39, 40, and 57, regardless of what specific laminopathy the human subject may initially have (i.e., if the patient has HGPS, they may be treated for the laminopathy of aging, heart disease, etc.; the symptoms of HGPS substantially overlap in scope with patient populations at claims 39, 40, and 57). This is pertinent because the applicable patient population at the pending claims includes any human subject “having [any] laminopathy” (i.e., aging), that would benefit from the treatment or prevention of any enumerated condition, including “aging”, “osteoporosis”, “deafness”, “heart disease”, “tooth disease”, “skin diseases”, “neuromuscular disease”, “muscle disease”, etc. (see, e.g., instant claim 40). Stated alternatively, the preamble phrase “of treating or preventing a laminopathy” is a recitation of an intended or expected result (see, e.g., MPEP §§ 2111.02(II), 2111.04(I)), which is understood to be fully satisfied by any prior art method that teaches the positively recited, active method steps set forth in the body of claim 37 (i.e., any method comprising the steps of administering via any route in any subject any “effective” amount of any “LINC complex inhibitor” to any subject). This means that the added phrase “wherein the laminopathy is not Hutchinson-Gilford Progeria Syndrome (HGPS)” does not limit the applicable patient population, but instead merely limits the intended use statement of the preamble (see, e.g., MPEP § 2111.04(I), noting that claim scope is not limited by claim language that does not require steps to be performed or by claim language that does not limit a claim to a particular structure). The Examiner’s interpretation is supported by at least the following two rationales:
First, the interpretation is supported by simply asking “Does the method exclude a patient having HGPS (and associated symptoms) but that is need of treatment or prevention of additional, non-HGPS laminopathies such as “aging”, “osteoporosis”, “deafness”, “heart disease”, “tooth disease”, “skin diseases”, “neuromuscular disease”, “muscle disease”, etc.?” (see, e.g., instant claim 40). The answer is “yes”. Accordingly, even patients having HGPS would still be treated under the current claim, because they would still benefit from treatment of other, non-HGPS laminopathies enumerated at claim 40. Therefore, the claim does not reasonably exclude patients having HGPS or at risk of HGPS, because such patients would still be treated for other laminopathies.
Second, instant dependent claims 40 and 57 continues to recite that the laminopathy may be or include other forms of “progeria”3 or any type of “progeroid Features”4. Therefore, the claim scope of claim 37 includes treatment and prevention of progeria and progeroid features in subjects. Accordingly, even patients with HGPS would continue to be treated by the method of amended claim 37, but would be treated for “Progeroid features” or other laminopathies.
In summary, the recitation of “wherein the laminopathy is not Hutchinson-Gilford Progeria Syndrome (HGPS)” attempts to limit an intended and expected result only, but fails to actually alter, change, or limit the applicable patient population of the claim in any way, because patients with HGPS would still be treated by the claimed method for the treatment of other laminopathies or for the treatment of “progeroid features” or additional, non-HGPS laminopathies such as “aging”, “osteoporosis”, “deafness”, “heart disease”, “tooth disease”, “skin diseases”, “neuromuscular disease”, “muscle disease”, etc. Accordingly, instant claim 37 encompasses: any method involving the treatment of any subject by administering (via any route) any “LINC complex inhibitor” within the scope of claim 37, at any “effective amount”.
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
All prior rejections are withdrawn in view of Applicant’s amendments and replaced with the following rejections, wherein all new or revised claim rejections were necessitated by Applicant’s amendments as filed 9/26/2025.
New or Revised Claim Rejections, as Necessitated by Applicant’s amendments
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 37, 39-40, 47-48, 50, and 57 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.
Amended claim 37 recites the negative proviso "wherein the laminopathy associated with mutation to LMNA is not Hutchinson-Gilford Progeria Syndrome (HGPS)” at the final two lines. There is insufficient antecedent basis for this limitation in the claim because claim 37 recites an intended and expected result in the preamble at lines 1-2 (i.e., “treating or preventing a laminopathy associated with mutation to LMNA in a human subject”) and recites a patient population receiving treatment (i.e., “a human subject having a laminopathy associated with mutation to LMNA”), and it is unclear whether the negative proviso is meant to limit the scope of the preamble or to limit the scope of the patient population being treated. For purposes of applying prior art, the negative proviso is understood to limit the preamble, and therefore the method does not exclude patients having HGPS, but wherein the intended laminopathy cannot be HGPS, but may be a related laminopathy, such as “aging”.
Claim 37 recites the administration of a “an amount sufficient to show therapeutic or prophylactic benefit”, which is a functionally defined amount of a functionally-defined compound for the treatment of an unspecified “laminopathy associated with mutation to LMNA” in a human subject, wherein the “amount” is presumably sufficient to treat one, more than one, or all laminopathies recited at dependent claims 39-40 and 57. MPEP § 2173.05(c)(III) is pertinent to the analysis of the phrase “an amount sufficient to show therapeutic or prophylactic benefit” because it pertains to analogous phrases including an “effective amount”. MPEP § 2173.05(c)(III) explains that such phrases, including “effective amount”, may be indefinite when one skilled in the art could not determine specific values for the amount based on the disclosure. Per MPEP § 2173.05(c)(III),
The phrase "an effective amount . . . for growth stimulation" was held to be definite where the amount was not critical and those skilled in the art would be able to determine from the written disclosure, including the examples, what an effective amount is. In re Halleck, 422 F.2d 911, 164 USPQ 647 (CCPA 1970). The phrase "an effective amount" has been held to be indefinite when the claim fails to state the function which is to be achieved and more than one effect can be implied from the specification or the relevant art. In re Fredericksen, 213 F.2d 547, 102 USPQ 35 (CCPA 1954).
Here, the “amount” appears to be critical to the invention, and “those skilled in the art would [not] be able to determine from the written disclosure, including the examples, what an effective amount is”, because (i) the instant phrase “an amount sufficient to show therapeutic or prophylactic benefit” does not actually correspond to any specific value or range of values in the original disclosure, (ii) zero examples of any amount sufficient to show therapeutic or prophylactic benefit in any human subject was disclosed on record; (iii) all three of the compound administered, the patient treated, and the disease to be treated or prevented are all variable and functionally defined, but impact the “amount” required5; and (iv) the Specification even admits that “[t]he actual amount administered, and rate and time-course of administration , will depend on the nature and severity of the disease to be treated/prevented, and the nature of the LINC complex inhibitor” (see, e.g., Spec. filed 1/13/2022 at 39 at line 35 to p. 40 at line 9), but fails to provide specific guidance regarding the usage of any particular species or subgenus of compound for use in treating any particular species or subgenus of patient for the treatment of any particular species or subgenus of disease using any particular route of administration. Accordingly, the “amount” renders the method indefinite because no specific result is recited, no specific compound is required, no specific patient population is required, and no specific route of administration is required, although the Specification admits such aspects impact “the amount administered”6. Accordingly, an artisan is left to just “guess” what actual concentrations define the metes and bounds of the Applicant’s invention. This is pertinent because MPEP § 2173 identifies that “[t]he primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent”, and here the boundaries of what does or does not constitute infringement are unknown. For purposes of applying prior art, any “amount” of any nucleic acid encoding any protein within the scope of instant claims 47-48 given to any patient suffering from “aging”, is understood to satisfy the amended claim scope.
At claim 37, the phrase “a dominant-negative SUN domain-containing protein that binds to a KASH domain-containing protein and thereby competitively inhibits interaction between an endogenous SUN domain-containing protein and an endogenous KASH domain-containing protein” provides a functional description of an unknown structure capable of achieving the desired and hoped for function, but fails to meaningfully correspond to any clear structure/function relationship of record permitting an artisan to meaningfully identify the metes and bounds of structures that do (or do not) constitute such a “dominant-negative Sun-domain-containing protein”. At best, the originally filed disclosure identifies that some unspecified structures from non-patent literature allegedly fall within the functionally defined genus of instant claim 37 (see, e.g., Spec. filed 1/13/2022 at 22 at line 34 to p. 23 at line 6). However, zero referenced documents appear to contain the claimed phrase as it appears in the instant claims7. Per MPEP § 2173.05(g), 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. 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. Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008). Similarly, here close prior art exists (see rejections below under 35 USC 102 and/or 103), and it is unknown whether or not a unique sequence sharing 45%, 55%, 69%, etc. sequence identity with instant SEQ ID NOs: 82-87, 97-101, and 113 constitute a “dominant-negative” within the scope of instant claim 37 or not. Furthermore, it is unknown whether or not all possible sequences sharing 70%, 75%, 80%, 90%, 95%, etc. sequence identity with instant SEQ ID NOs: 82-87, 97-101, and 113 constitute a “dominant-negative” within the scope of instant claim 37, or if only some of these sequences satisfy the functional language of the claim, but not all. Per MPEP § 2173, “the primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent”, and here the pending claims fail to meaningfully inform artisans of what structures do or do not fall within the pending claim scope. For purposes of applying prior art, the functionally defined genera of structures at instant claim 37 are understood to include all possible nucleic acids encoding any proteins or polypeptides comprising or consisting of sequences sharing at least 70% sequence identity to any one of SEQ ID NOs: 82-87, 97-101 or 114 (see, e.g., Spec. filed 1/13/2022 at 23 at line 34 to p. 24 at line 2, p. 24 at line 39 to p. 25 at line 8).
At claim 37, the phrase “a dominant-negative KASH domain-containing protein that binds to a SUN domain-containing protein and thereby competitively inhibits interaction between an endogenous SUN domain-containing protein and an endogenous KASH domain-containing protein” provides a functional description of an unknown structure capable of achieving the desired and hoped for function, but fails to meaningfully correspond to any clear structure/function relationship of record permitting an artisan to meaningfully identify the metes and bounds of structures that do (or do not) constitute a “dominant-negative KASH domain-containing protein” capable of the recited function. At best, the originally filed disclosure identifies that some unspecified structures from non-patent literature allegedly fall within the functionally defined genus of instant claim 37 (see, e.g., Spec. filed 1/13/2022 at 22 at line 34 to p. 23 at line 6). However, zero referenced documents appear to contain the claimed phrase as it appears in the instant claims8. Per MPEP § 2173.05(g), 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. 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. Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008). Similarly, here close prior art exists (see rejections below under 35 USC 102 and/or 103), and it is unknown whether or not a unique sequence sharing 45%, 55%, 69%, etc. sequence identity with instant SEQ ID NOs: 82-87, 97-101, and 113 constitute a “dominant-negative” within the scope of instant claim 37 or not. Furthermore, it is unknown whether or not all possible sequences sharing 70%, 75%, 80%, 90%, 95%, etc. sequence identity with instant SEQ ID NOs: 82-87, 97-101, and 113 constitute a “dominant-negative” within the scope of instant claim 37, or if only some of these sequences satisfy the functional language of the claim, but not all. Per MPEP § 2173, “the primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent”, and here the pending claims fail to meaningfully inform artisans of what structures do or do not fall within the pending claim scope. For purposes of applying prior art, the functionally defined genera of structures at instant claim 37 are understood to include all possible nucleic acids encoding any proteins or polypeptides comprising or consisting of sequences sharing at least 70% sequence identity to any one of SEQ ID NOs: 82-87, 97-101 or 114 (see, e.g., Spec. filed 1/13/2022 at 23 at line 34 to p. 24 at line 2, p. 24 at line 39 to p. 25 at line 8).
Amended claim 39 recites “the laminopathy associated with mutation to LMNA” at lines 1-2. There is insufficient antecedent basis for this limitation in the claim because claim 37 recites an intended and expected result in the preamble at lines 1-2 (i.e., “treating or preventing a laminopathy associated with mutation to LMNA in a human subject”) and recites a patient population receiving treatment (i.e., “a human subject having a laminopathy associated with mutation to LMNA”). Therefore, there is insufficient antecedent basis for this limitation in the claim because it is unclear whether the phrase “the laminopathy associated with mutation to LMNA” at dependent claim 39 is meant to limit the scope of the preamble or to limit the scope of the patient population being treated. For purposes of applying prior art, dependent claim 39 is understood to limit the preamble of claim 37, and therefore claim 39 limits the intended and expected use of the independent claim rather than the patient population receiving the compound.
Amended claim 40 recites “the laminopathy associated with mutation to LMNA” at lines 1-2. There is insufficient antecedent basis for this limitation in the claim because claim 37 recites an intended and expected result in the preamble at lines 1-2 (i.e., “treating or preventing a laminopathy associated with mutation to LMNA in a human subject”) and recites a patient population receiving treatment (i.e., “a human subject having a laminopathy associated with mutation to LMNA”). Therefore, there is insufficient antecedent basis for this limitation in the claim because it is unclear whether the phrase “the laminopathy associated with mutation to LMNA” at dependent claim 40 is meant to limit the scope of the preamble or to limit the scope of the patient population being treated. For purposes of applying prior art, dependent claim 40 is understood to limit the preamble of claim 37, and therefore claim 40 limits the intended and expected use of the independent claim rather than the patient population receiving the compound.
Newly added claim 57 recites “the laminopathy associated with mutation to LMNA” at lines 1-2. There is insufficient antecedent basis for this limitation in the claim because claim 37 recites an intended and expected result in the preamble at lines 1-2 (i.e., “treating or preventing a laminopathy associated with mutation to LMNA in a human subject”) and recites a patient population receiving treatment (i.e., “a human subject having a laminopathy associated with mutation to LMNA”). Therefore, there is insufficient antecedent basis for this limitation in the claim because it is unclear whether the phrase “the laminopathy associated with mutation to LMNA” at dependent claim 57 is meant to limit the scope of the preamble or to limit the scope of the patient population being treated. For purposes of applying prior art, dependent claim 57 is understood to limit the preamble of claim 37, and therefore claim 57 limits the intended and expected use of the independent claim rather than the patient population receiving the compound.
Claims 39-40, 47-48, 50, and 57 depend directly or indirectly from an indefinite base claim, and these claims fail to clarify the indefiniteness of the independent claim. Therefore, such claims are rejected as indefinite for the reasons applicable to claims 37 above.
Claims 37, 39-40, 47-48, 50, and 57 are rejected as indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 40 and 57 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Amended claim 37 excludes HGPS at the final line. However, dependent, amended claim 40 and newly added claim 57 continue to recite “progeria” at line 2, which encompasses HGPS (or is otherwise synonymous with HGPS). Accordingly, dependent claims 40 and 57 are rejected for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 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 37, 39-40, 47-48, 50, and 57 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.
Claim Scope
Claim 37 is representative of the pending claims scope and recites a method of “treating or preventing a laminopathy associated with mutation to LMNA in a human subject, comprising administering nucleic acid encoding a LINC complex inhibitor to a human subject having a laminopathy associated with mutation to LMNA in an amount sufficient to show therapeutic or prophylactic benefit to the human subject” by administering9 (via any route) to a functionally-defined compound of unspecified structure at a functionally defined “amount”, wherein a “laminopathy” is defined to include highly distinctive conditions ranging from “aging”, “osteoporosis”, “deafness”, “Progeroid Features”, “heart disease”, “tooth disease”, “skin diseases”, “neuromuscular disease”, “muscle disease”, etc, etc.. (see, e.g., instant claims 37. 39-40, 57, and Spec. filed 1/13/2022 at 49 at line 29 to page 50 at line 25).
It is unclear if the claimed methods encompass trillions of species of treating numerous diseases (aging, osteoporosis, tooth disease, heart disease, skin disease, muscle disease, etc.), via numerous forms of administration (e.g., topical, anal, oral, intramuscular, intravenous, etc.), in numerous patient populations having some unspecified “laminopathy associated with mutation to LMNA”, by administering unknown nucleic acids encoding unknown and functionally-defined “dominant negative” structures at unknown and unspecified “amounts” sufficient to achieve some unknown and unspecified “therapeutic or prophylactic benefit” to a human subject; or if the claimed methods include only one or two treatable diseases in a limited patient population and via limited routes of administration using a very limited number of possible protein structures. Accordingly, the claim scope appears to be vast and highly varied.
Actual Reduction to Practice
Zero species of the claimed invention, wherein any substance was administered to a human subject at any dosage to achieve any benefit was reduced to practice.
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.
As described above, and explained below, the scope of the instant claims is vast and highly varied. 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 zero species of the claimed invention does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus.
Ill-defined Structure/Function Relationships
Amended claim 37 recites the following functionally described genera:
“[A] dominant-negative SUN domain-containing protein that binds to a KASH domain-containing protein and thereby competitively inhibits interaction between an endogenous SUN domain-containing protein and an endogenous KASH domain-containing protein”; and also
“[A] dominant-negative KASH domain-containing protein that binds to a SUN domain-containing protein and thereby competitively inhibits interaction between an endogenous SUN domain-containing protein and an endogenous KASH domain-containing protein”.
This functional language fails to correspond to a clear, unambiguous structure/function relationship of record, but instead such language refers to unknown and ill-described structures capable of achieving the desired and hoped-for function recited in the amended claims.
Although the originally filed disclosure identifies that some unspecified structures from non-patent literature that may allegedly fall within the functionally defined genera of instant claim 37 (see, e.g., Spec. filed 1/13/2022 at 22 at line 34 to p. 23 at line 6), zero referenced documents appear to contain the claimed phrase as it appears in the instant claims. Furthermore, such non-patent documents cannot be incorporated by reference since they are directed to essential subject matter (see, e.g., 37 C.F.R. 1.57(c), (d)).
Although the originally filed disclosure alleges that some unspecified polypeptides “may behave as a dominant-negative peptide/polypeptide” (see id. at 23 at line 30, p. 24 at line 35-26). It is unclear if all possible sequences comprising or consisting of sequences sharing at least 70% sequence identity with instant SEQ ID NOs: 82-87, 97-101, and 113 constitute a “dominant-negative” protein within the scope of amended claim 37, or not, because the Specification fails to provide clear guidance whether all such structures constitute “dominant-negative” proteins as required by amended claim 37 or not (see, e.g., Spec. filed 1/13/2022 at 22 at line 34 to p. 24 at line 2, p. 24 at line 39 to p. 25 at line 8).
Here close prior art exists (see rejections below under 35 USC 103), and it is prima facie unknown whether a unique sequence sharing 45%, 55%, 69%, etc. sequence identity with instant SEQ ID NOs: 82-87, 97-101, and 113 constitutes a “dominant-negative” within the scope of instant claim 37 or not. Furthermore, it is unknown whether all possible sequences sharing 70%, 75%, 80%, 90%, 95%, etc. sequence identity with instant SEQ ID NOs: 82-87, 97-101, and 113 constitute a “dominant-negative” within the scope of instant claim 37, or if only some of these sequences satisfy the functional language of the claim, but not all.
The failure to provide a clear structural definition of what compounds do or do not constitute a “dominant-negative [KASH or SUN] domain-containing protein” is a violation of the written description requirement. 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).
Here, Applicants have claimed a broad and highly varied genus of methods utilizing an unknown number of potentially highly distinct and ill-defined species only by reference to one or more functional limitations and improper incorporation by reference of essential matter (see, e.g., 37 C.F.R. 1.57(c), (d)), However, the originally filed disclosure and the prior art of record fails to clearly and unambiguously 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.
Ill-defined Dosages
Amended claim 37 recites and requires that an unspecified and functionally-described compound is administered via an unspecified route of administration at “an amount sufficient to show therapeutic or prophylactic benefit” of an unspecified condition10. Accordingly, the dosage utilized is functionally-defined and depends upon the “therapeutic or prophylactic benefit” desired, the patient population treated, the actual compound utilized, and the duration of frequency of treatment (see, e.g., Spec. filed 1/13/2022 at 39 at line 35 to p. 40 at line 9).
Accordingly, the claimed phrase amounts to a recitation of a hoped-for and desired result, wherein Applicant leaves it to future inventors to actually discover novel, workable ranges and “an amount sufficient” or “effective” for particular compounds, patient populations, particular routes of administration, and particular “benefits”.
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 full scope of the pending claims because zero methods of administering a polypeptide topically, anally, vaginally, orally, etc. and “treating” or “preventing” the scope of claimed laminopathies (i.e., “aging”, “osteoporosis”, “deafness”, “Progeroid Features”, “heart disease”, “tooth disease”, “skin diseases”, “neuromuscular disease”, “muscle disease”, etc.; see, e.g., instant claims 37-41, Spec. filed 1/13/2022 at 49 at line 29 to page 50 at line 25) was actually reduced to practice. Furthermore, unlike Biogen, here the pending claims further attempt to draw a fence around the treatment of unknown and potential diseases and conditions that may subsequently be deemed a “laminopathy” in the future, utilizing ill-described and unknown compounds administered via all possible routes of administration, in any patient populations. Accordingly, the claims are substantially broader than those at issue in Biogen, and less supporting evidence appears in the specification relative to 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 in a particular patient population would be “effective” for the preventing or treating any particular “laminopathy” as presently claimed.
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). In addition, 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; 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, or what dos