DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-2, 8, 12, 14-15, 17-21, 24-26, 28, 32, 34-35, 38, and 50 are pending. No amendments were filed correcting issues noted in the Requirement mailed 3/19/2026 at page 2.
Claims 19-21, 24-26, 28, 32, 34, 35, and 38 are directed to non-elected inventions of Groups II-III. Claims 2, 8, 12, and 14 are directed to non-elected species. Claims 2, 8, 12, 14, 19-21, 24-26, 28, 32, 34, 35, and 38 are withdrawn.
Claims 1, 15, 17-18, and 50 are presently considered.
Election/Restriction
Applicant’s election without traverse of Group I (products; claims 1-2, 8, 12, 14-15, 17, 18, and 50 as filed 12/26/2023) in the reply filed on 5/18/2026 is acknowledged.
Applicant's election with traverse of the species of Example 1 at page 20 (COL-4 solution comprising 90 µl of 12 mg/ml COL-IV dissolved in 0.1 M acetic acid, combined with 1.8 µl of 5 M NaOH, 7.3µl of 27.4 mg/mL CaCl2 and 0.1 mg of riboflavin) of the Specification filed 9/15/2023 in the reply filed on 5/18/2026 is acknowledged. The traversal is on the grounds that (i) the Examiner “must identify the species for which election is required with sufficient clarity to permit a meaningful election and response”, which allegedly “did not occur here” (see, e.g., Reply filed 5/18/2026 at 3-4 at § II); (ii) that the species election “does not track the claim set” or “establish that Group I contains independent inventions requiring separate examination” (see, e.g., Reply filed 5/18/2026 at 3-4 at § II); (iii) that the Requirement did not establish that the alleged species lack a single general inventive concept or otherwise that the compositions of claim 1 fail to define a special technical feature for purposes of PCT Rules 13.1 and 13.2 (see, e.g., Reply filed 5/18/2026 at 3-4 at § II). These arguments are not found persuasive because
(i) per MPEP § 809.02(a), Examiner need not “clearly identify” all possible species; furthermore, although Examiner invited Applicant to contact the Examiner if additional clarification was needed (see Requirement mailed 3/19/2026 at 8), Applicant failed to avail themselves of this opportunity for clarification. Finally, such arguments are not credible because the claim scope clearly recites alternative and optional components that unique species may consist of, and examiners are permitted to assume the requirements of 37 C.F.R. § 11.101 and 11.7(a)(2) are met.
(ii) Applicant fails to identify any legal support requiring a species election to “track the claim set”. In contrast to this assertion, Examiner directed Applicant to cited MPEP explaining that requiring election of a “single, disclosed species”1 is proper, and may be carried out as explained at MPEP § 809.02(a), which explains that “[t]he species are preferably identified as the species of . . . examples I, II, [etc.]”; notably, the requirement explicitly required identification of an example or figure (see Requirement mailed 3/19/2026 at pages 4, 5, 7 at bullet point labeled “first”). Accordingly, no requirement that a species election “track” a claim set has been identified by Applicant; however, such a requirement would not be reasonable because claim sets (and claim scope) typically change during the course of prosecution, but the originally elected species does not change to “track” such changes.
(iii) An explanation explaining lack of inventive step among inventions and among the species of claim 1 was set forth in the Requirement (see Requirement mailed 3/19/2026 at 9-10). If Applicant means to allege that all species sharing the recited limitations at instant claim 1 are patentably indistinct relative to each other (i.e., obvious variants), Applicant should so clearly admit on record that all species within the scope of claim 1 are obvious variants of one another. If such an admission is set forth on record, then the species election will be withdrawn. However, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species. At this time, no such admission has been placed on record, and it is the Examiner’s position that each species within the scope of claim 1, which clearly differ by specific components present (e.g., crosslinker selected, presence or absence of additional components, etc.) are patentably distinct in the absence of evidence to the contrary.
Accordingly, the species lack inventive step in view of the prior art for reasons of record, species were identified as required by MPEP § 809.02(a), and no admission has been placed on record that all species of claim 1 are obvious variants. Therefore, in the absence of admission that the species of obvious variants, the traversal is not persuasive. In addition, Applicant is directed to the additional rejections and prior art made of record, below, which clearly establish that claim 1 does not define a special technical feature for purposes of PCT Rules 13.1 and 13.2.
The requirement is still deemed proper and is therefore made FINAL.
The originally elected species is understood as follows: The originally elected species is understood to be the composition and concentrations set forth for “COL-4” at Table 1 at “Example One” (see, e.g., Spec. filed 9/15/2023 at 20). Specifically, the elected species of composition is understood to consist of a solution comprising 90 µl of 12 mg/ml COL-IV dissolved in 0.1 M acetic acid, combined with 1.8 µl of 5 M NaOH, 7.3µl of 27.4 mg/mL CaCl2 and 0.1 mg of riboflavin. The final volume is understood to be approximately 100 µl (see, e.g., Spec. filed 9/15/2023 at 20-21, noting that Table 1 adds up to 99.1µl +0.1 mg of riboflavin, and 100 µl solutions are referenced at page 21). Accordingly, the final COL-4 solution is understood to be approximately 10.8 mg/ml2 of COL-IV, approximately 0.09 M (or 90 mM) sodium ions3, approximately 2.0 mg/mL of CaCl24 (i.e., 0.018 M or 18.02 mM of calcium ions), to have a pH of between 6.7 and 7.4 (see, e.g., Spec. filed 9/15/2023 at 20-21), and to comprise riboflavin at approximately 0.0008 mg/mL (0.8 µg/mL or 2.13 µM)5.
The originally elected species is understood to read upon instant claims 1, 15, 17-18, and 50. At claim 15, NaOH and CaCl2 are ionic salts. At claim 17, the elected species falls within the range of claim 17(i), but outside the ranges of 17(ii) or 17(iii). At claim 18, the elected species falls within the ranges recited. At claim 50, the kit “comprises” the enumerated components, which may be in combination as recited at claim 1.
However, the originally elected species does not read upon all claims of Group I. Claims 2 and 8 require the limitations of claim 2, which recites fibrinogen and/or thrombin and/or mammalian cells, which was not identified as present in the originally elected species; therefore claims 2 and 8 do not read upon the originally elected species. Claims 12 and 14 require one or more additional components, but no enumerated components were identified as present in the originally elected species; therefore claims 12 and 14 do not read upon the originally elected species. Accordingly, claims 2, 8, 12, and 14 are directed to non-elected species.
Following extensive search and examination, the originally elected species has been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 1, 15, 17-18, and 50 are rejected in view of the originally elected species and claims that do not read upon the originally elected species are withdrawn.
Claims 19-21, 24-26, 28, 32, 34, 35, and 38 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 5/18/2026.
Claims 2, 8, 12, and 14 are 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. Applicant timely traversed the restriction (election) requirement in the reply filed on 5/18/2026.
Accordingly, claims 1, 15, 17-18, and 50 are presently considered.
Priority
Priority to AU2021900794, as filed 3/18/2021, is acknowledged.
Information Disclosure Statement
No IDS has been filed on record.
It is noted that the duty of disclosure, candor, and good faith is applicable to named inventors, each attorney or agent that prepares or prosecutes, and all persons substantively involved in the preparation or prosecution of the application, and who are associated with the inventor, the applicant, an assignee, or anyone to whom there is an obligation to assign the application (see, e.g., 37 C.F.R. 1.63(c) and 37 C.F.R. 1.56).
For example, any documents (posters, dissertations, talks, publications, etc.) known to Applicant (including documents from co-pending applications) pertaining to any collagen in combination with sodium and/or calcium ions, with riboflavin or other cross-linkers are relevant to patentability and should be placed on record in an IDS.
Specification
The disclosure is objected to because of the following informalities:
Figure 6 is described as showing colors (red, green, blue), but no colors are shown (i.e., images are in grayscale) (see, e.g., Spec. filed 9/15/2023 at 11 at penultimate ¶, 25 at 1st partial ¶).
Figure 8 is described as showing colors (blue), but no colors are shown (see, e.g., Spec. filed 9/15/2023 at 12 at 1st full ¶).
Appropriate correction is required.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show colors as described in the specification. Specifically, Figure 6 is described as showing colors (red, green, blue), but no colors are shown (i.e., images are in grayscale) (see, e.g., Spec. filed 9/15/2023 at 11 at penultimate ¶, 25 at 1st partial ¶). In addition, Figure 8 is described as showing colors (blue), but no colors are shown (see, e.g., Spec. filed 9/15/2023 at 12 at 1st full ¶). 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 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 1 is representative of the pending claim scope and presently recites:
1. (Original) A composition comprising:
- 6-24 mg/ml type IV collagen;
- 0.04-0.15 M sodium ions and/or 0.008-0.4 M calcium ions; and
- one or more crosslinking agents.
Accordingly, the original claim scope is directed to a product, namely a composition. Additional claim interpretations are discussed 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)).
“Type IV collagen” is understood to encompass “unmodified” and “modified” Type IV collagen (see, e.g., Spec. filed 9/15/2023 at 13 at 3rd full ¶). The modification of “modified” Type IV collagen is unlimited.
Sodium ions may be obtained from any source, including sodium chloride (see, e.g., Spec. filed 9/15/2023 at 13 at penultimate ¶).
Calcium ions may be obtained from any source, including calcium chloride (see, e.g., Spec. filed 9/15/2023 at 13 at penultimate ¶).
“One or more cross-linking agents” is understood to any art-recognized crosslinking agents, including at least riboflavin, which is disclosed for use at 0.01-0.5% (w/v) or 0.01-0.1 mg (see, e.g., Spec. filed 9/15/2023 at 10 at 5th full ¶, 14 at final ¶).
“The type IV collagen is neutralised” is understood to require that the pH of the solution is adjusted to between 6.7 and 7.6 in view of the originally filed disclosure (see, e.g., Spec. filed 9/15/2023 at 10 at 3rd full ¶).
A “kit” is understood to be any “delivery system for delivering materials”, including appropriate containers and materials such as buffers (see, e.g., Spec. filed 9/15/2023 at 9 at 5th full ¶).
Additional claim interpretations are discussed below.
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 15 and 50 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 15 recites “and/or the type IV collagen is neutralized”, which appears to be a process step recited in a product claim, and therefore renders the claim scope indefinite (see, e.g., Spec. filed 9/15/2023 at 10 at 3rd full ¶, noting that the phrase is understood to require that the pH of the solution is adjusted to between 6.7 and 7.6 in view of the originally filed disclosure). Per MPEP § 2173.05(p)(II), a single claim which claims a product and method steps involving the product is indefinite because it is unclear if infringement occurs before, during, or after the completion of the method step. If Applicant means to limit the pH range of the composition, Applicant may directly recite that the composition further comprises a pH within a specific range.
Claim 50 is directed to a “kit, package or device for preparing a composition” in the preamble, but the body of the claim only describes a kit (e.g., “the kit comprising” at lines 1-5). Accordingly, claim 50 is indefinite because it is missing limitations defining the metes and bounds of “package or device for preparing a composition”, and therefore does not reflect the preamble of the claim. Applicant may overcome this rejection by amending claim 50 to recite “A kit, the kit comprising….” and deleting the reference to a “package or device for preparing a composition”.
Accordingly, claims 15 and 50 are rejected.
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.
Claim 18 is 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.
Claim 18 depends from claim 1, but recites broader ranges of type IV collagen, sodium ions, and calcium ions relative to instant claim 1 (e.g., “less than 24 mg/ml” encompasses 0.01 mg/ml; “more than 0.04 M” includes 100 M; “more than 0.008 M” includes 100 M). Accordingly, claim 18 is rejected under 35 USC 112(d) as being of improper dependent form 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 § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
[Prior Art Rejection 01]
Claims 1, 15, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over WO2014147622A1 (Sept. 25, 2014; Grynspan et al.) in view of Lee et. al6.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 15, and 50, WO’622 pertains to compositions comprising collagen, an inorganic salt such as CaCl2, and a cross-linker (see, e.g., WO’622 at claims 1-5), wherein an artisan would readily appreciate that the collagen may be crosslinked before or after the addition of the inorganic salt (see, e.g., WO’622 at claims 23-26, 29, and 33; see also WO’622 at p. 17 at lines 19-33 explaining that “the crosslinking may be effected following the addition of the inorganic salts”; see also id. at 18 at lines 29-31 referring to “crosslinked or non-crosslinked collagen”). Regarding instant claims 1, 15, 50, and the concentration of collagen, WO’622 identifies that the collagen may be present at “about 10-50 mg/ml” (see, e.g., WO’622 at claims 13-14), which overlaps in scope with the instantly claimed range (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”). Regarding instant claims 1, 15, 50, and the presence of calcium ions, WO’622 identifies that the inorganic salt may be selected from NaCl and CaCl2 (see, e.g., WO’622 at claims 1-4), wherein calcium chloride may be present at a concentration of “about 7-60 mM” (see, e.g., WO’622 at claim 15, p. 17 at lines 1-10), which overlaps in scope with the instantly claimed range (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”). Regarding instant claims 1, 15, 50, and the presence of “one or more crosslinking agents”, WO’622 contemplates the usage of various crosslinking agents, and explicitly identifies that “the crosslinking may be effected following the addition of the inorganic salts” (see, e.g., WO’622 at p. 17 at lines 19-33), wherein the exemplified crosslinking agents include photoinitiators, genipin, EDC, etc. (see, e.g., WO’622 at p. 17 at lines 19-33). Regarding instant claim 15, CaCl2,is understood to be an ionic salt (see, e.g., WO’622 at claim 15).
The disclosure of WO’622 differs from the instant claim scope as follows: WO’622 directs artisans to utilize collagen, generally, but does not explicitly teach or reduce to practice a composition comprising collagen Type IV.
However, regarding the usage of collagen Type IV, although WO’622 does not expressly teach collagen Type IV, an artisan would readily appreciate that such collagens were within the scope of WO’622 and contemplated in view of the disclosure. Specifically, WO’622 explicitly teaches that the collagen may be any human or recombinant collagen (see, e.g., WO’622 at claims 8 and 11; see also id. at 9 at line 8 to page 12 at line 10), including any collagen “having a triple helix structure and containing a repeating Gly-X-Y triplet”, or a homolog of human collagen (see, e.g., WO’622 at 9 at line 8 to p. 10 at lines 17, Table 1 at 9). Accordingly, an artisan would readily appreciate that WO’622 read upon and encompassed all human collagens.
Lee discloses that Collagen Type IV was known in the prior art and was a human collagen (see, e.g., Lee at title, abs, 1 at col I-II at § Introduction, Table 1 on p. 2), and identifies that Collagen Type IV and other collagens were recognized in the bioprinting art, and understood to be suitable for use in collagen bioprinting applications (see, e.g., Lee at title, abs, Table 1 on p. 2, p. 4 at Fig. 2).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the obvious combination of prior art elements (e.g., a known collagen, known calcium containing ionic salt, and a known crosslinker) according to known methods of forming collagen compositions for use in tissue regeneration applications, exactly as taught and suggested by the primary reference, wherein such combination would yield predictable results, namely the composition would yield a collagen composition suitable for use in the tissue regeneration methods taught and disclosed by the primary reference. Furthermore, each prior art element would merely perform its art-recognized function in combination as it does separately (see, e.g., MPEP §§ 2143(I)(A), (G); see also MPEP § 2144.05(II), noting “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”, and here no such evidence has been presented commensurate in scope with the instant claims, and all components are merely present within overlapping ranges already taught and disclosed by the prior art, therefore finding optimal concentrations of known components within known ranges is prima facie obvious per MPEP § 2144.05(I); see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to simply combine known prior art elements in known combinations within known concentration ranges to obtain compositions exactly as taught by the prior art, wherein such compositions would be expected and predicted to have the same utility taught and disclosed by the prior art.
Accordingly, claims 1, 15, and 50 are rejected.
[Prior Art Rejection 02]
Claims 1, 15, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over WO2018/225076A1 (Zarka et al.; Dec. 13, 2018) in view of Lee et. al7.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
WO’076 pertains to the usage of collagen-containing formulations suitable for use in additive manufacturing applications (see, e.g., WO’076 at title, abs, 1 at lines 10-18, 46 at lines 29-34). Regarding instant claims 1, 15, 50, and the usage of collagen in combination with riboflavin, WO’076 claims formulations comprising a “human recombinant human collagen featuring at least one curable group” (see, e.g., WO’076 at claims 29-30, 33), wherein a human collagen is broadly defined (see, e.g., WO’076 at 22 at line 16 to page 23 at line 27), and “at least one curable group” , wherein the curable groups are understood to include naturally occurring functional moieties and additionally wherein such curable groups “can be generated by means of chemical reactions with other chemical compounds (see, e.g., WO’076 at 32 at line 25 to page 33 at line 6; see also id. at 38-39 at bridging ¶), which is understood to include photocurable groups (see, e.g., WO’076 at 33 at lines 9-12), wherein the photocurable materials include a photoinitiator, which may be riboflavin (see, e.g., WO’076 at 45 at lines 15-17, 45 at lines 27-29). Accordingly, and artisan would readily appreciate that a human collagen in combination with a photoinitiator like riboflavin would constitute a human collagen with “at least one curable group” (see, e.g., WO’076 at claims 29-30 and 33, at page 32 at line 25 to page 33 at line 12, page 45 at lines 15-17, page 45 at lines 27-29). Regarding instant claims 1, 15, 50, and the concentration of collagen utilized, WO’076 explicitly directs artisans to utilize collagen in a broad range of “0.5 mg/mL to 50 mg/mL” or a narrower range of “5 mg/mL to 15 mg/mL” (see, e.g., WO’076 at page 36 at lines 17-22, claim 35; see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”). Regarding the aqueous carrier and a pH range, WO’076 explicitly teaches that the claimed formulations may comprise an aqueous carrier (see, e.g., WO’076 at claims 29-30, 33), and further disclose that the aqueous carrier may have a pH from “about 7 to about 7.4” (see, e.g., WO’076 at page 35 at lines 4-6). Regarding instant claims 1, 15, 50, and the usage and presence of sodium ions from ionic salts at a concentration between 0.04 M to 0.15 M, WO’076 explicitly teaches that the claimed formulations may comprise an aqueous carrier (see, e.g., WO’076 at claims 29-30, 33), and further disclose that the aqueous carrier may may comprise “NaCl or any other physiologically acceptable salt”, at a concentration of “about 0.1 mM to about 0.1 M” (see, e.g., WO’076 at page 35 at lines 3-24). Accordingly, utilizing an aqueous carrier having NaCl (i.e., sodium ions) at a concentration of “about 0.1 mM to about 0.1 M” would be obvious (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”). Regarding instant claim 50 and a “kit”, WO’076 explicitly teaches, discloses, and claims kits (see, e.g., WO’076 at claims 27-28, page 8 at lines 8-14, page 48 at line 15 to line 32), and therefore an artisan would readily appreciate that the individual or combined components could be utilized in a “kit”.
The disclosure of WO’076 differs from the instant claim scope as follows: WO’076 directs artisans to utilize a human collagen, generally, but does not explicitly teach or reduce to practice a composition comprising collagen Type IV.
However, regarding the usage of collagen Type IV, although the primary reference does not expressly teach collagen Type IV, WO’076 explicitly teaches that the disclosed invention may be utilized with any “collagen”, wherein a collagen is any “polypeptide having a triple helix structure and containing a repeating Gly-X-Y triplet, where X and Y can be any amino acid but are frequently the imino acids proline and hydroxyproline” and includes homologs of collagen sequence listed at Table A, which includes homologs of human collagens (see, e.g., WO’076 at 22 at line 16 to page 23 at line 27). Accordingly, an artisan would readily appreciate and conclude that the disclosure of the primary reference could be predictably utilized with any human collagen.
Lee discloses that Collagen Type IV was known in the prior art and was a human collagen (see, e.g., Lee at title, abs, 1 at col I-II at § Introduction, Table 1 on p. 2), and identifies that Collagen Type IV and other collagens were recognized in the bioprinting art, and understood that such collagens were suitable for use in collagen bioprinting applications (see, e.g., Lee at title, abs, Table 1 on p. 2, p. 4 at Fig. 2).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the obvious combination of prior art elements (e.g., a known human collagen, a known sodium ion containing aqueous carrier, and a known cross-linker of riboflavin) according to known methods of forming collagen compositions for use in additive manufacturing applications, exactly as taught and suggested by the primary reference, wherein such combination would yield predictable results, namely the composition would yield a collagen-containing composition suitable for use in additive manufacturing methods taught and disclosed by the primary reference. Furthermore, each prior art element would merely perform its art-recognized function in combination as it does separately (see, e.g., MPEP §§ 2143(I)(A), (G); see also MPEP § 2144.05(II), noting that “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”, and here no such evidence has been presented commensurate in scope with the instant claims, and all components are merely present within overlapping ranges already taught and disclosed by the prior art, therefore finding optimal concentrations of known components within known ranges is prima facie obvious per MPEP § 2144.05(I); see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to simply combine known prior art elements in known combinations within known concentration ranges to obtain compositions and formulations exactly as taught by the prior art, wherein such compositions or formulations would be expected and predicted to have the same utility and applications explicitly taught and disclosed by the prior art.
Accordingly, claims 1, 15, and 50 are rejected.
[Prior Art Rejection 03]
Claims 1, 15, 17-18, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over WO2018/225076A1 (Zarka et al.; Dec. 13, 2018) in view of Lee et. al8.as applied to claims 1, 15, and 50 above, and further in view of Thomson-Luque et al.9.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of WO’076 in view of Lee as applied to claims 1, 15, and 50 have been set forth above in a preceding rejection, and those teachings are incorporated into the instant rejection. The instant rejection addresses embodiments comprising both sodium and calcium ions.
The pending claim scope differs from the prior art of WO’076 and Lee as follows: The pending claim scope encompasses embodiments comprising both sodium and calcium ions, but WO’076 in view of Lee does not explicitly recite the usage of both ions simultaneously. However, such difference would be obvious.
Regarding aqueous carriers and salt ions generally, WO’076 explicitly teaches that the claimed formulations may comprise an aqueous carrier (see, e.g., WO’076 at claims 29-30, 33), wherein the aqueous carrier may comprise physiologically acceptable salts over a range of “about 0.1 mM to about 0.2 M” (see, e.g., WO’076 at page 35 at lines 3-24). This is pertinent because WO’076 fairly informs artisans that a wide range of salt concentrations could be utilized successfully in additive manufacturing formulations (see id.). To this end, WO’076 informs artisans that aqueous carrier may utilize commercially available buffers such as RPMI 1640, McCoy 5A, etc. (see, e.g., WO’076 at 35 at lines 3-24, 36 at lines 5-13).
Regarding calcium an sodium ions: Critically, commercially available buffers are well-known in the prior art, and frequently contain both calcium and sodium ions, and therefore an artisan would readily and reasonably appreciate that the additive manufacturing formulations of WO’076 could contain both calcium and sodium ions, wherein the total physiological salts remained within a range of “about 0.1 mM to about 0.2 M” (see, e.g., WO’076 at page 35 at lines 3-24). For example, Thomson-Luque provides a comparison of RPMI 1640 and McCoy5A buffers (see, e.g., Thomson-Luque at Table 1 on 8), and the comparison identifies that RPMI1640 and McCoy5A may be formulated slightly different by different providers, but that such buffers contain both calcium and sodium ions, wherein such buffers comprise approximately ~133 to 146 mM of sodium ions (i.e., ~0.133 M to ~0.146 M), and approximately ~0.42 mM to 0.90 mM of calcium ions (i.e., 0.00042 M to 0.00090 M). Accordingly, in view of the guidance at WO’076, an artisan would readily appreciate that the claimed formulations could comprise an aqueous carrier (see, e.g., WO’076 at claims 29-30, 33), wherein the aqueous carrier could comprise physiologically acceptable salts over a range of “about 0.1 mM to about 0.2 M” (see, e.g., WO’076 at page 35 at lines 3-24), wherein WO’076 provides direct guidance to utilize inorganic salts comprising both sodium and calcium ions by reference to RPMI 1640, McCoy5A, and other buffers (see, e.g., WO’076 at 35 at lines 3-24, 36 at lines 5-13) as would be understood by an artisan (see, e.g., Thomson-Luque at Table 1 on 8). Accordingly, simply utilizing or simply substituting buffers such as McCoy5A for the aqueous carrier of WO’076 would be readily understood to yield compositions having sodium and calcium ions within the ranges presently claimed (see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): Here, the claimed invention is the known combination of known components (i.e., known human Collagen Type IV, known sodium and calcium ions derived from inorganic salts, and a known crosslinker of riboflavin) combined according to known methods of forming known compositions predicted and expected to be suitable for use in additive manufacturing methodologies exactly as taught and suggested by the primary reference in view of Lee and Thomson-Luque (see, e.g., (see, e.g., MPEP §§ 2143(I)(A), (G); MPEP § 2144.05(I)). Regarding the differences in specific concentrations of individual components within the ranges disclosed by the primary reference, it has long been settled that "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation" (see, e.g., Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955); see also MPEP 2144.05(II)), because "[n]o invention is involved in discovering optimum ranges of a process by routine experimentation" (see, e.g., Application of Aller at 458, 105 USPQ at 236-237; see also MPEP 2144.05(II); See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382, explaining that "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed … range is the optimum combination…”; In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929), explaining that "It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions"). Here, since Applicant has not disclosed that the specific range limitations recited in the instant claims are for any particular purpose or solve any stated problem and the prior art teaches that physiological salts, including calcium and sodium salts, may be varied to predictably and desirably obtain formulations suitable for use in additive manufacturing applications as taught by the primary reference, and such parameters are understood to work equivalently in the absence of unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of physiological salts for use in collagen-containing additive manufacturing formulations disclosed by the primary reference by normal optimization procedures known in the collagen-containing additive manufacturing formulation arts.
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to simply combine known prior art elements in known combinations within known concentration ranges to expectantly and predictably obtain compositions and formulations exactly as taught by the prior art, wherein such compositions or formulations would be expected and predicted to have the same utility and applications explicitly taught and disclosed by the prior art.
Accordingly, claims 1, 15, 17-18, and 50 are rejected.
[Prior Art Rejection 04]
Claims 1, 15, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019/211873A2 (Sangwan et al.; Nov. 07, 2019) in view of Lee et. al10.
Regarding instant claims 1, 15, 50, and a composition comprising collagen in combination with calcium ions and a cross-linker, WO’873 discloses compositions comprising a polymer at 17 to 110 mg/mL, which may be any form of collagen (see, e.g., WO’873 at claims 1-3), wherein the composition further comprises calcium chloride and a cross-linker (see, e.g., WO’873 at claims 1-3, 13-15), wherein the cross-linker may be selected from cross-linkers enumerated therein (see, e.g., WO’873 at claim 13), and wherein the calcium ion concentration may be 7.5 to 50 mM (i.e., 0.0075 M to 0.05 M). Accordingly, the disclosed concentration ranges overlap with the instantly claimed ranges (see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
The disclosure of the primary reference differs from the instant claim scope as follows: Although the primary reference directs artisans to utilize any collagen, generally, the reference does not explicitly teach or reduce to practice a composition comprising collagen Type IV.
Lee discloses that Collagen Type IV was known in the prior art and was a human collagen (see, e.g., Lee at title, abs, 1 at col I-II at § Introduction, Table 1 on p. 2), and identifies that Collagen Type IV and other collagens were recognized in the bioprinting art, and understood that such collagens were suitable for use in collagen bioprinting applications (see, e.g., Lee at title, abs, Table 1 on p. 2, p. 4 at Fig. 2).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the obvious combination of prior art elements (e.g., a known collagen, a known calcium ion containing aqueous carrier, and a known cross-linker) according to known methods of forming liquid cornea compositions, exactly as taught and suggested by the primary reference, wherein such combination would yield predictable results, namely the composition would yield liquid cornea compositions suitable for use the methods taught and disclosed by the primary reference. Furthermore, each prior art element would merely perform its art-recognized function in combination as it does separately (see, e.g., MPEP §§ 2143(I)(A), (G); see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to simply combine known prior art elements in known combinations within known concentration ranges to obtain compositions and formulations exactly as taught by the prior art, wherein such compositions or formulations would be expected and predicted to have the same utility and applications explicitly taught and disclosed by the prior art.
Accordingly, claims 1, 15, and 50 are rejected.
[Prior Art Rejection 05]
Claims 1, 15, 17-18, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019/211873A2 (Sangwan et al.; Nov. 07, 2019) in view of Lee et. al11 as applied to claims 1, 15, and 50 above, and further in view of Appendix12
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of WO’873 in view of Lee as applied to claims 1, 15, and 50 have been set forth above in a preceding rejection, and those teachings are incorporated into the instant rejection. The instant rejection addresses embodiments comprising both sodium and calcium ions.
The pending claim scope differs from the prior art of WO’873 and Lee as follows: The pending claim scope encompasses embodiments comprising both sodium and calcium ions, wherein sodium ions are present at 0.04-0.15 M; although WO’873 in view of Lee directs artisans to formulations utilizing calcium ions, WO’873 does not explicitly recite the usage of both ions simultaneously, wherein sodium ions are present within the range of at 0.04-0.15 M. However, an artisan would readily appreciate that such difference was obvious in view of the guidance and direction of the primary reference and general knowledge of buffers.
WO’873 explicitly teaches, discloses, and directs artisans to make and use liquid cornea compositions comprising buffer solutions, and explicitly directs artisans to utilize PBS, and specifically PBS (1X) or diluted PBS (0.4-0.6X) (see, e.g., WO’873 at ¶[0082]).
Appendix is cited herein to establish that PBS was well-known in the prior art (see, e.g., Appendix at A.2A.4 at “PBS (phosphate-buffered saline)”). 1X PBS is understood to comprise 137 mM NaCl, and 4.3 mM Na2HPO4 (see id.) which yields a total of approximately ~145.6 mM (i.e., ~137 mM + ~2*4.3 mM). However, 0.4-0.6X PBS as suggested by WO’873 would only comprise approximately 58.24 mM to 87.36 mM sodium ions (see, e.g., WO’873 at ¶[0082]; see also Appendix at A.2A.4 at “PBS (phosphate-buffered saline)”), which may be written as 0.05824 M to 0.08736 M. In view of guidance to include 1XPBS (~0.1456 M sodium ions) or 0.4-0.6X PBS (~0.05824 M to 0.08736 M sodium ions) (see, e.g., WO’873 at ¶[0082]), an artisan would readily appreciate that PBS could be included in liquid cornea compositions using at least the combined range of 0.4X-1X PBS with a reasonable expectation of success (e.g., ~0.05824 M to ~0.1456 M sodium ions) (see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”). Accordingly, the simultaneous presence of both sodium and calcium ions in the liquid cornea formulations of WO’873 would necessarily result from simply following the explicit guidance of the primary reference, and including PBS buffer in the formulations.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the obvious combination of prior art elements (e.g., a known collagen, a known calcium ion containing aqueous carrier, PBS at 0.4X to 1X, and a known cross-linker) according to known methods of forming liquid cornea compositions, exactly as taught and suggested by the primary reference, wherein such combination would yield predictable results, namely the composition would yield liquid cornea compositions suitable for use the methods taught and disclosed by the primary reference. Furthermore, each prior art element would merely perform its art-recognized function in combination as it does separately (see, e.g., MPEP §§ 2143(I)(A), (G); see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to simply combine known prior art elements in known combinations within known concentration ranges to obtain compositions and formulations exactly as taught by the prior art, wherein such compositions or formulations would be expected and predicted to have the same utility and applications explicitly taught and disclosed by the prior art.
Accordingly, claims 1, 15, 17-18, and 50 are rejected.
[Prior Art Rejection 06]
Claims 1, 15, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020/205645 (Bachrach et al.; Oct. 087, 2020) in view of Appendix13
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 15, 50, and compositions comprising 6-24 mg/ml of type IV collagen, WO’645 discloses “tissue or organ replacement compositions” comprising “bio ink compositions”, wherein the bio ink compositions may comprise collagen (see, e.g., WO’645 at claims 1-2), wherein collagen is present at “about 5 mg/ml to about 200 mg/ml” (see, e.g., WO’645 at claims 1-2, 5), and wherein the collagen is selected from type IV collagen (see, e.g., WO’645 at claims 5-6). Regarding instant claims 1, 15, 50, and compositions comprising “one or more crosslinking agents”, such as riboflavin, WO’645 explicitly teaches and claims that the bio ink compositions may comprise a crosslinking agent (see, e.g., WO’645 at claims 1-2, 5-6, and 8), which may be riboflavin and/or calcium (see, e.g., WO’645 at ¶[0036]). Regarding instant claims 1, 15, 50, and inorganic salts, WO’645 explicitly teaches and claims that the bio ink compositions may comprise a “carrier” (see, e.g., WO’645 at claims 1-2, 5-6, and 8), which may be any “aqueous ionic salt solution”, including “Phosphate Buffer saline (PBS)”, “Hanks balanced salt solution”, etc. (see, e.g., WO’645 at ¶¶[0044], [0095], [0100]).
The primary reference differs from the pending claim scope as follows: Although WO’645 directs artisans to bio inks comprising “about 5 mg/ml to about 200 mg/ml” of collagen IV, a crosslinker such as riboflavin, and a carrier, WO’645 does not explicitly teach a particular range of sodium ions.
However, WO’645 explicitly teaches and claims that the bio ink compositions may comprise a “carrier” (see, e.g., WO’645 at claims 1-2, 5-6, and 8), which may be an “aqueous ionic salt solution”, “Phosphate Buffer saline (PBS)”, “Hanks balanced salt solution”, etc. (see, e.g., WO’645 at ¶¶[0044], [0095], [0100]). Appendix establishes that 1X PBS comprises 137 mM NaCl, and 4.3 mM Na2HPO4 (see, e.g., Appendix at A.2A.4 at “PBS (phosphate-buffered saline)”) which yields a total of approximately ~145.6 mM (i.e., ~137 mM + ~2*4.3 mM) (see, e.g., Appendix at A.2A.4 at “PBS (phosphate-buffered saline)”). In addition, or alternatively, Appendix establishes that “Hanks balanced salt solution” (HBSS) comprises approximately 0.3 mM Na2HPO4, 4.2 mM NaHCO3, NaCl (137 mM final), or approximately 141.8 mM sodium ions (0.3mM*2 + 4.2mM +137 mM) (see, e.g., Appendix at A.2A.4 at “HBSS (Hanks’ balanced salt solution”) and 1.3 mM calcium ions from CaCl2 (see id.). Accordingly, an artisan simply utilizing a bioink as claimed and described in combination with PBS of HBSS would necessarily obtain a bio ink formulation comprising approximately 141.8 mM to 145.6 mM sodium ions, which is between 0.04-0.15 M sodium ions as presently claimed (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the obvious combination of prior art elements (e.g., a collagen IV, the aqueous carrier comprising sodium ions of either HBSS or PBS, and a known cross-linker of riboflavin) according to known methods of forming bio ink compositions, exactly as taught and suggested by the prior art, wherein such combinations would yield predictable results, namely a bio ink compositions suitable for use in the methods and applications taught and disclosed by the primary reference; furthermore, each prior art element would merely perform its art-recognized function in combination as it does separately (see, e.g., MPEP §§ 2143(I)(A), (G); see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to simply combine known prior art elements in known combinations within known concentration ranges to obtain compositions and formulations exactly as taught by the prior art, wherein such compositions or formulations would be expected and predicted to have the same utility and applications explicitly taught and disclosed by the prior art.
Accordingly, claims 1, 15, and 50 are rejected.
[Prior Art Rejection 07]
Claims 1, 15, 17-18, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020/205645 (Bachrach et al.; Oct. 087, 2020) in view of Appendix14 as applied to claims 1, 15, and 50 above, and further in view of Pang et al.15
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of WO’645 in view of Appendix as applied to claims 1, 15, and 50 have been discussed above in a preceding rejection, and those teachings are incorporated herein.
The teachings of the primary reference in view of Appendix differs from species of claims 1, 15, 17-18, and 50, that are within the scope of instant claims 17-18 as follows: Although WO’645 directs artisans to bio inks comprising “about 5 mg/ml to about 200 mg/ml” of collagen IV, a crosslinker such as riboflavin, and a carrier comprising “aqueous ionic salt solution” such as “Phosphate Buffer saline (PBS)”, and “Hanks balanced salt solution”, WO’645 does not explicitly teach a the instantly claimed range of calcium ions and sodium ions as recited at instant claims 17-18.
Regarding calcium ions and sodium ions, WO’645 explicitly teaches and claims that the bio ink compositions may comprise a “carrier” (see, e.g., WO’645 at claims 1-2, 5-6, and 8), which may be any “aqueous ionic salt solution”, including “Phosphate Buffer saline (PBS)”, “Hanks balanced salt solution”, etc. (see, e.g., WO’645 at ¶¶[0044], [0095], [0100]). An artisan would readily appreciate that such “aqueous ionic salt solutions” could include different amounts of both sodium and calcium ions (e.g., compare PBS, HBSS, “cell media”; see, e.g., Appendix at A.2A.4 at “HBSS (Hanks’ balanced salt solution”), wherein sodium and calcium ions could range from 0 mM each (see, e.g., WO’645 at ¶[0095], reciting phosphate buffer solutions; see, e.g., Appendix at A.2A.5 to A.2A.6 at Phosphate Buffer, noting 0 mM of calcium or sodium) up to at least 141.8 mM sodium ions (0.3mM*2 + 4.2mM +137 mM) (see, e.g., Appendix at A.2A.4 at “HBSS (Hanks’ balanced salt solution”) and 1.3 mM calcium ions from CaCl2 (see id.) in HBSS. Accordingly, varying sodium ions from 0 to 141.8 mM would be readily understood in view of WO’645 and Appendix to be reasonable amounts of sodium ions in collagen IV bioinks. However, calcium ion levels are discussed in WO’645 as both present within the carrier solution (e.g., HBSS), and also used as crosslinkers (see, e.g., WO’645 at ¶¶[0036], [0097], referring to calcium levels as controlling crosslinking rates). The exact amount of calcium ions required to act as a crosslinker or otherwise modify the crosslinking rate of a collagen bio ink is not specified. In addition, Pang is cited herein to establish that calcium ions would be reasonably and readily expected to impact collagen structure (see, e.g., Pang at title, abs, 5 at § Discussion, explaining that calcium ions impact the structural and mechanistic characteristics of a homologous type of collagen).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The specific concentration ranges of sodium and calcium ions are obvious per routine optimization in the collagen bioink arts, in view of the disclosure of WO’645, Appendix, and Pang, which direct artisans to compositions comprising collagen type IV, crosslinkers (e.g., riboflavin, calcium), and aqueous ionic salt solutions comprising calcium and sodium ions, because "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation" (see, e.g., Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955); see also MPEP 2144.05(II)), because "[n]o invention is involved in discovering optimum ranges of a process by routine experimentation" (see, e.g., Application of Aller at 458, 105 USPQ at 236-237; see also MPEP 2144.05(II); See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382, explaining that "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed … range is the optimum combination…”; In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929), explaining that "It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions"); and herein the prior art teaches that sodium ions may be present within an overlapping range (see MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”), and the prior art teaches that calcium ions may be present in different amounts, wherein calcium ions impact crosslinking rates and collagen structures, and therefore are result-effective variables, and since Applicant has not disclosed that the specific limitations recited in instant claims are for any particular purpose or solve any stated problem and the prior art teaches that calcium ion levels may vary, and other parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the collagen bio ink arts (see MPEP § 2144.05(I)-(II)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to simply combine known prior art elements in known combinations within known (or routinely optimizable) concentration ranges to obtain compositions and formulations exactly as taught by the prior art, wherein such compositions or formulations would be expected and predicted to have the same utility and applications explicitly taught and disclosed by the prior art.
Accordingly, claims 1, 15, 17-18, and 50 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 1, 15, 17-18, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10, 11-12, 15-16, and 44 of copending Application No. 17/756,147 (corresponding to US20230001047A1) in view of WO2018/225076A1 (Zarka et al.; Dec. 13, 2018) as explained below. This is a provisional nonstatutory double patenting rejection.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
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 paragraph16: 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”. Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
The copending claim sets are each understood to be directed to collagen gel formulations comprising:
(1) 6-15 mg/mL of collagen (compare instant claims 1, 15, 17-18, 50 with App’147 at claim 1, 14, 15-16);
(2) 0.135-0.15 M sodium ions (compare instant claims 1, 15, 17-18, 50 with App’147 at claim 1, 11, 15-16);
(3) 0.008-0.4 M calcium ions (compare instant claims 1, 15, 17-18, 50 with App’147 at claim 1, 11, 15-16);
(4) an overlapping range of crosslinkers such as riboflavin or Rose Bengal (compare instant claims 1, 50 with App’147 at claim 1); wherein
(5) the compositions may further comprise additional components (compare instant claims 1, 50 with App’147 at claims 1, 8, 10, 12, 44).
Accordingly, the copending claim sets are directed to an overlapping combination of collagen, sodium ions, calcium ions, crosslinkers, and optionally additional components (see also MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
The copending claim sets differ as follows: The copending claim sets differ with respect to the specific collagen recited. Specifically, the instant Application recites and requires “type IV collagen”, but the App’147 recites “type I collagen”. Accordingly, the relevant question is whether or not the simple substitution of one collagen type for another in a collagen gel formulation renders the copending claim scopes patentable distinct in view of the art.
However, regarding the usage of collagen Type I or IV, although the primary reference does not expressly teach collagen Type IV, WO’076 fairly informs artisans that collagen compositions suitable for use in additive manufacturing methodologies (e.g., curable collagen gels) could be utilized with any “recombinant human collagen” (see, e.g., WO’076 at claim 25-26), wherein a collagen would be readily understood to be any “polypeptide having a triple helix structure and containing a repeating Gly-X-Y triplet, where X and Y can be any amino acid but are frequently the imino acids proline and hydroxyproline”, including homologs of collagen sequence listed at Table A (see, e.g., WO’076 at 22 at line 16 to page 23 at line 27). Accordingly, an artisan would readily appreciate and conclude that the collagen I and IV (i.e., known human collagens) could be utilized as functionally equivalent human collagens in compositions utilized for additive manufacturing of collagen-based materials.
Accordingly, the differences between the reference claims and instant claims appear to be minor at best because both claim sets read upon substantially identical formulations of collagen-comprising compositions that differ only by the specific type of human collagen protein utilized17; and therefore the answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”18 is clearly “yes”.
MPEP § 804(II)(B)(2)-(3) further identify 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)). Here, under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is the Examiner’s position the copending claim sets are directed to patentably indistinct collagen gel formulations, wherein such formulations differ only by the simple substitution of one known human collagen peptide for another known human collagen peptide, wherein an artisan in view of the prior art of WO’076 would readily appreciate that such formulations could be made utilizing any human collagen protein with a reasonable expectation of successfully achieving a usable collagen gel formulation (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(I)(A)-(D), MPEP § 2144.05(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
Accordingly, instant claims 1, 15, 17-18, and 50 are provisionally rejected on the ground of nonstatutory double patenting
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
You et al.19 teaches and discloses corneal gel compositions comprising collagen dissolved in 0.1 M acetic acid, neutralized with 5 M NaOH to reach pH 7.3-7.6, followed by addition of Na+ ions, to yield a 5.4 mg/mL solution that was mixed with 0.1% riboflavin (see, e.g., You at abs).
US5436135 claims collagen gels “consisting essentially of type IV collagen” (see, e.g., US’135 at title, abs, claim 14).
US 5639654 claims skin substitutes comprising type I and IV collagen, riboflavin, and salts (see, e.g., US’654 at title, abs, claims 14, 19-20, Table 1 noting the presence of riboflavin).
US 8,338,375 pertains to an injectable dermal filler prepared by combining a collagen selected from collagen type I, II, III, IV, or V; and treating the collagen with a crosslinking agent, wherein the crosslinking forms a gel (see, e.g., US’375 at claim 1).
US2012/0230977A1 (Sep. 13, 2012) pertains to crosslinking protocols for collagen (see, e.g., US’977 at title, abs, Fig. 2A).
WO2018/022548 discloses collagen gels comprising collagen, a crosslinker, and MES buffer or aqueous buffer comprising sodium ions (see, e.g., WO’548 at 23 at lines 8-21, 25 at lines 20-25).
Kleinman et al.20 discloses MATRIGEL, which is a commonly utilized gel in the prior art comprising substantial amounts of collagen Type IV (see, e.g., Kleinman et al. at title, abs, 379 at col I at Table 1).
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 see, e.g., MPEP § 809.02(a), identifying that “[t]he species are preferably identified as the species of . . . examples I, II, [etc.]” and that “Applicant should then be required to elect a single disclosed species”; see, e.g., MPEP § 814(I), referring to “a particular disclosed species”; see, e.g., MPEP § 803.02(III)(A), noting that the “examiner should set forth a requirement for election of a single disclosed species”; see, e.g., MPEP § 808.01(a), noting that “applicant must elect a single disclosed species”; note that per MPEP § 809.02(a), Examiner need not “clearly identify” all possible species.
2 Note that 90 µl of 12 mg/ml added to a final volume of 100 µl, is understood to have a final concentration of approximately 10.8 mg/ml (e.g., C1V1 = C2V2).
3 Note that 1.8 µl of 5 M NaOH added to yield a final volume of 100 µl, is understood to have a final concentration of approximately 0.09 M NaOH (e.g., C1V1 = C2V2).
4 Note that Mass is concentration x volume, and (e.g., C1V1 = C2V2), and therefore the final amount of CaCl2 (MW = 110.98 g/mol) is initially (27.4 mg/mL x 7.3 µL) = (92.7µl + 7.3µl)(C2), which yields 2.0 mg/mL, which is 0.018M (18.02 mM).
5 Note that Mass is concentration x volume, and (e.g., C1V1 = C2V2), and therefore the final amount of riboflavin (MW = 376.36 g/mol) is initially (0.1 mg/mL x 0.8 µL) = (99.2µl + 0.8µl)(C2), which yields 0.0008 mg/mL, which is 2.13 µM (Molarity = [0.0008 mg/ml] / (MW)).
6 Lee et al., Bioprinting of Collagen: Considerations, Potentials, and Applications. Macromol Biosci. 2021 Jan;21(1):e2000280. doi: 10.1002/mabi.202000280. Epub 2020 Oct 19. PMID: 33073537; hereafter “Lee”; cited in Requirement mailed 3/19/2026.
7 Lee et al., Bioprinting of Collagen: Considerations, Potentials, and Applications. Macromol Biosci. 2021 Jan;21(1):e2000280. doi: 10.1002/mabi.202000280. Epub 2020 Oct 19. PMID: 33073537; hereafter “Lee”; cited in Requirement mailed 3/19/2026.
8 Lee et al., Bioprinting of Collagen: Considerations, Potentials, and Applications. Macromol Biosci. 2021 Jan;21(1):e2000280. doi: 10.1002/mabi.202000280. Epub 2020 Oct 19. PMID: 33073537; hereafter “Lee”; cited in Requirement mailed 3/19/2026.
9 Thomson-Luque et al., From marginal to essential: the golden thread between nutrient sensing, medium composition and Plasmodium vivax maturation in in vitro culture. Malar J. 2019 Oct 10;18(1):344. doi: 10.1186/s12936-019-2949-x. PMID: 31601222; PMCID: PMC6785855.
10 Lee et al., Bioprinting of Collagen: Considerations, Potentials, and Applications. Macromol Biosci. 2021 Jan;21(1):e2000280. doi: 10.1002/mabi.202000280. Epub 2020 Oct 19. PMID: 33073537; hereafter “Lee”; cited in Requirement mailed 3/19/2026.
11 Lee et al., Bioprinting of Collagen: Considerations, Potentials, and Applications. Macromol Biosci. 2021 Jan;21(1):e2000280. doi: 10.1002/mabi.202000280. Epub 2020 Oct 19. PMID: 33073537; hereafter “Lee”; cited in Requirement mailed 3/19/2026.
12 Common stock solutions, buffers, and media. Curr Protoc Neurosci. 2001 May; Appendix 2:Appendix 2A. doi: 10.1002/0471142301.nsa02as00. PMID: 18428446; hereafter “Appendix”.
13 Common stock solutions, buffers, and media. Curr Protoc Neurosci. 2001 May; Appendix 2:Appendix 2A. doi: 10.1002/0471142301.nsa02as00. PMID: 18428446; hereafter “Appendix”.
14 Common stock solutions, buffers, and media. Curr Protoc Neurosci. 2001 May; Appendix 2:Appendix 2A. doi: 10.1002/0471142301.nsa02as00. PMID: 18428446; hereafter “Appendix”.
15 Pang et al., Unraveling the role of Calcium ions in the mechanical properties of individual collagen fibrils. Sci Rep. 2017 Apr 5;7:46042. doi: 10.1038/srep46042. PMID: 28378770; PMCID: PMC5380965; hereafter “Pang”.
16 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.”
17 See, e.g., 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.
18 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.”
19 You et al., Development of a simple method to generate transparent collagen gel compatible with corneal cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4142; cited in Requirement mailed 3/19/2026.
20 Kleinman et al., Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol. 2005 Oct;15(5):378-86. doi: 10.1016/j.semcancer.2005.05.004. PMID: 15975825.
Prosecution Insights